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Sample records for basal serum calcitonin

  1. Benefit of measuring basal serum calcitonin to detect medullary thyroid carcinoma in a Danish population with a high prevalence of thyroid nodules

    DEFF Research Database (Denmark)

    Hasselgren, Martin; Hegedüs, Laszlo; Godballe, Christian

    2009-01-01

    ; thyroidectomy was performed in 307 of these patients. RESULTS: Thirty-nine patients had elevated serum calcitonin; 6 of these patients had MTC detected by the initial diagnostic setup. No additional patient in the cohort was registered in the Danish Thyroid Cancer Database, reflecting that all patients with MTC......BACKGROUND: Routine measurement of serum calcitonin to detect medullary thyroid carcinoma (MTC) continues to be fiercely debated, although less attention has been paid to the positive predictive value (PPV) of this method. METHODS: We collected data from 959 patients with nontoxic nodular goiter....... The low PPV might lead to unnecessary thyroid surgery. Thus, the result of serum calcitonin measurement should always be interpreted in the context of other clinical variables. (c) 2009 Wiley Periodicals, Inc. Head Neck, 2009....

  2. Radioimmunoassay of calcitonin in unextracted human serum: a sensitive method

    Energy Technology Data Exchange (ETDEWEB)

    Emmertsen, K.; Marqversen, J.; Jensen, F.T.; Hansen, H.H. (Kommunehospitalet, Copenhagen (Denmark))

    1982-11-01

    A sensitive sequential direct radioimmunoassay of calcitonin (CT) is described. Human synthetic monomer CT was used for /sup 125/I-labelling. The antibody was directed against mid-portion and C-terminal parts of the human CT molecule. No significant cross reactivity with salmon or porcine CT was found. Separation of free from antibody-bound /sup 125/I-labelled CT was performed using a double antibody-polyethyleneglycol mixture. Dilution curves of sera from normal controls and patients with medullary thyroid carcinoma (MCT) were parallel to the standard curve. The intraassay coefficients of variation (CV) were 6% and 3% at serum concentrations of 90 and 230 ng/l respectively. The interassay CV were 13% and 10% at mean serum CT concentrations of 50 and 210 ng/l respectively. The lower limit of detection was 20 ng/l. Thirty-one healthy controls had serum CT levels in the range of 35-135 ng/l. Elevated basal serum CT concentrations were found in 11 patients with MCT and the serum concentrations increased markedly after pentagastrin stimulation. Subsequent thyroidectomy in eight of the 11 patients with MCT reduced basal serum CT levels, in six to within the reference range for normals.

  3. The effects of fasting and refeeding on serum parathormone and calcitonin concentrations in young and old male rats.

    Science.gov (United States)

    Kmieć, Z; Myśliwski, A; Wyrzykowska, M; Hoppe, A

    2001-05-01

    Although fasting and refeeding reveal the existence of age-related changes in carbohydrate and lipid metabolism, the effects of aging on mineral metabolism in refed animals are unknown. We therefore investigated hormonal regulation of calcium metabolism in young (4 months) and old (26 months) male rats fasted for 48 hours and then refed for 4 or 24 hours. Serum concentrations of total and ionized calcium and parathormone were similar in control young and old rats. Serum calcitonin level was higher, and the concentrations of albumin and inorganic phosphate and alkaline phosphatase activity were lower in fed old rats. In young fasted rats, the serum ionized and total calcium was decreased, and phosphate concentration was increased. In old rats, fasting resulted in the increase of serum parathormone level. Fasting reduced serum alkaline phosphatase activity to a similar extent in both age groups. In young rats, refeeding for 24h normalized serum calcium and phosphate levels and alkaline phosphatase activity, and decreased serum concentrations of PTH and calcitonin. In old refed rats, serum calcitonin concentration was raised by 77% compared to fed or fasted animals, whereas parathormone levels were normalized. Our results indicate that old fasted or refed rats maintain normal serum calcium concentration in a different way than young animals, possibly through the increase in serum levels of parathormone and/or calcitonin. Thus, dietary manipulations such as fasting and refeeding constitute an interesting model for the investigation of the effects of aging on the hormonal regulation of serum calcium level.

  4. Pentagastrin, calcium and whisky stimulated serum calcitonin in medullary carcinoma of the thyroid.

    Science.gov (United States)

    Emmertsen, K K; Nielsen, H E; Mosekilde, L; Hansen, H H

    1980-01-01

    The efficiency of pentagastrin, calcium and whisky in raising serum immunoreactive calcitonin (S-iCT) concentrations was analysed in 6 patients with medullary carcinoma of the thyroid and in 8 healthy controls. All 6 patients responded to pentagastrin with a significant increase in S-iCT, 5 responded to calcium and only 3 to whisky. In the 8 controls no or only a modest increase in S-iCT occurred following pentagastrin, calcium and whisky with no difference between the three. It is concluded that pentagastrin is the most useful stimulative agent for ICT secretion in patients with C-cell neoplasms. In selected cases the additional use of calcium could be advantageous.

  5. Determination of calcitonin; Bestimmung von Kalzitonin

    Energy Technology Data Exchange (ETDEWEB)

    Goerges, R. [Klinik fuer Nuklearmedizin, Klinikum Essen, Univ. Duisburg/Essen (Germany); Gemeinschaftspraxis fuer Nuklearmedizin, Duisburg (Germany)

    2005-03-01

    Calcitonin in serum is a comparatively highly sensitive, specific and reliable tumor marker of central relevance for the diagnosis and follow-up of medullary thyroidal C-cell carcinoma (MTC) and neoplastic C-cell hyperplasia (CCH). It is seen considerably less often in other tumor entities. For determination we recommend immunometric two-site assays of approximately 1-2 pg/ml sensitivity. Higher MTC specificity is achieved by assays focussing on a largely selective determination of monomeric calcitonin. If this is realized, basal calcitonin levels are already greatly relevant for MTC or CCH diagnosis. The diagnostic sensitivity and specificity of calcitonin determination may be further enhanced by means of pentagastrin test, but even then false positive results are clinically relevant especially in benign CCH and renal insufficiency. In family screening in case of MTC patients, moleculargenetic techniques have become the procedure of choice and have now largely replaced the pentagastrin test. Calcitonin screening in adenomatous goitre (struma nodosa) is making headway. Although this accounts for only 10% of thyroidal malignomas (which are in fact rare), and the recommended levels of intervention will result in many unnecessary surgical operations, early tumor staging definitely increases the chances for curative intervention. (orig.)

  6. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...

  7. False positive results using calcitonin as a screening method for medullary thyroid carcinoma

    Directory of Open Access Journals (Sweden)

    Rafael Loch Batista

    2013-01-01

    Full Text Available The role of serum calcitonin as part of the evaluation of thyroid nodules has been widely discussed in literature. However there still is no consensus of measurement of calcitonin in the initial evaluation of a patient with thyroid nodule. Problems concerning cost-benefit, lab methods, false positive and low prevalence of medullary thyroid carcinoma (MTC are factors that limit this approach. We have illustrated two cases where serum calcitonin was used in the evaluation of thyroid nodule and rates proved to be high. A stimulation test was performed, using calcium as secretagogue, and calcitonin hyper-stimulation was confirmed, but anatomopathologic examination did not evidence medullar neoplasia. Anatomopathologic diagnosis detected Hashimoto thyroiditis in one case and adenomatous goiter plus an occult papillary thyroid carcinoma in the other one. Recommendation for routine use of serum calcitonin in the initial diagnostic evaluation of a thyroid nodule, followed by a confirming stimulation test if basal serum calcitonin is showed to be high, is the most currently recommended approach, but questions concerning cost-benefit and possibility of diagnosis error make the validity of this recommendation discussible.

  8. Basal serum pancreatic polypeptide is dependent on age and gender in an adult population

    DEFF Research Database (Denmark)

    Brimnes Damholt, M; Rasmussen, B K; Hilsted, L;

    1997-01-01

    This study is the first epidemiologically based study of basal levels of serum pancreatic polypeptide (s-PP). The basal level of serum PP has become a field of interest mainly due to the role of PP as an endocrine tumour marker, and as a marker of pancreatic neuroendocrine function after pancreas...... a monospecific radioimmunoassay. Fasting serum pancreatic polypeptide depended on age and gender. The results demonstrated that fasting pancreatic polypeptide levels increase exponentially with age. Fitted separately for each sex, basal serum pancreatic polypeptide was found to increase by approximately 3% per...... reports on the fasting levels of serum pancreatic polypeptide are most likely due to lack of adjustment for age and gender. Thus, variation due to age and gender should be considered in evaluating fasting levels of serum pancreatic polypeptide. Whether similar considerations are important when evaluating...

  9. Early detection of response in small cell bronchogenic carcinoma by changes in serum concentrations of creatine kinase, neuron specific enolase, calcitonin, ACTH, serotonin and gastrin releasing peptide

    DEFF Research Database (Denmark)

    Bork, E; Hansen, M; Urdal, P;

    1988-01-01

    determined within 4-8 weeks. The results indicate that serum CK-BB and NSE are potential markers for SCC at the time of diagnosis and that changes in the concentrations during the first course of cytostatic therapy are promising as biochemical tests for early detection of response to chemotherapy.......Creatine kinase (CK-BB), neuron specific enolase (NSE), ACTH, calcitonin, serotonin and gastrin releasing peptide (GRP) were measured in serum or plasma before and immediately after initiation of treatment in patients with small cell lung cancer (SCC). Pretherapeutic elevated concentrations of CK...... stage patients and 71% in limited stage patients. Frequent initial monitoring of the substances showed an increase in the concentrations of pretherapeutic elevated CK-BB and NSE on day 1 or 2 followed by a sharp decrease within 1 week. These changes were correlated to objective clinical response...

  10. Association of basal serum testosterone levels with ovarian response and in vitro fertilization outcome

    Directory of Open Access Journals (Sweden)

    Sun Mei

    2011-01-01

    Full Text Available Abstract Background To evaluate basal testosterone (T levels during follicular phase of the menstrual cycle as a predictor for ovarian response and in vitro fertilization (IVF outcome. Method We analyzed data retrospectively from hospital-based IVF center including one thousand two hundred and sixty Chinese Han women under their first IVF cycle reached the ovum pick-up stage, without polycystic ovary syndrome (PCOS or endometriosis undergoing long IVF protocol. Patients were divided into 2 groups. Group 1: patients with diminished ovarian reserve (basal FSH >10 IU/L (n = 187; Group 2: patients with normal ovarian reserve (basal FSH Results Basal T levels were markly different between pregnant and non-pregnant women in Group 1; whereas not in Group 2. A testosterone level of 47.85 ng/dl was shown to predict pregnancy outcome with a sensitivity of 52.8% and specificity of 65.3%; and the basal T was correlated with the numbers of large follicles (> 14 mm on HCG day in Group 1. Significantly negative correlations were observed between basal T, days of stimulation and total dose of gonadotropins after adjusting for confounding factors in both groups. Conclusion In women with diminished ovarian reserve, basal T level was a predictor for the number of large follicles on HCG day and pregnancy outcome; but could not in those with normal serum FSH. Basal T levels were associated with both days of stimulation and total dose of gonadotropins, indicating that lower level of T might relate with potential ovarian poor response.

  11. Bivariate analysis of basal serum anti-Mullerian hormone measurements and human blastocyst development after IVF

    LENUS (Irish Health Repository)

    Sills, E Scott

    2011-12-02

    Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH) measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79) and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+\\/- SD) age for study patients in this study group was 36.3 ± 4.0 (range = 28-45) yrs, and mean (+\\/- SD) terminal serum estradiol during IVF was 5929 +\\/- 4056 pmol\\/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65) was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44) was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61), suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol\\/l; p = 0.029). Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.

  12. Prognostic Value of Basal Serum Thyroglobulin Levels, but Not Basal Antithyroglobulin Antibody (TgAb Levels, in Patients with Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Isa Neshandar Asli

    2014-06-01

    Full Text Available Objective: The prognostic values of serum thyroglobulin (Tg and antithyroglobulin antibody (TgAb levels, measured immediately before I-131remnant ablation in patients with differentiated thyroid cancer (DTC, have been advocated by some researchers; however, it had controversial outcomes. This study was carried out to examine this dilemma and to check the clinical significance of basal serum Tg and TgAb levels and postablation iodine 131whole body scan(WBS findings in DTC patients. Methods: In this retrospective study, the records of 500 patients with differentiated thyroid cancer, who had undergone treatment between 2003 and 2010, were assessed. Of those, 149 patients with results of basal serum thyroglobulin concentration and whole body scan using radioactive iodine were included. Age, sex, tumour histology, basal thyroglobulin (Tg, anti-thyroglobulin (TgAb and TSH concentration, radioactive iodine doses in each hospitalization, numbers of hospitalization, and results of whole body scans were recorded. The relationship among basal Tg, TgAb, TSH, and whole body scan with hospitalization number and total radioactive iodine doses were assessed. Results: A total of 149 patients, including 123 (83% females and 26 (17% males, with a mean age of 40±15 years, took part in the study. The mean (SD basal Tg, TgAb, and TSH were 91.7±169.2 ng/mL (0.1-1000 ng/mL, 250±893 U/mL (0-9000 U/m L, and 64.8±61.5 µU/mL (30-689 U/mLµ, respectively. A total of 52 (34.9% cases had TgAb levels greater than 100 U/mL. The mean basal Tg in patients who were admitted three or more times was significantly greater than that of patients with one hospitalization (p=0.026. In addition, the mean of Tg in patients who received 7.4 GBq radioactive iodine or less was significantly lower than the others (p=0.003. The mean of TgAb and TSH were not different between these groups. In the results of the whole body scans, patients with metastasis had higher frequency of

  13. Assays for calcitonin receptors

    Energy Technology Data Exchange (ETDEWEB)

    Teitelbaum, A.P.; Nissenson, R.A.; Arnaud, C.D.

    1985-01-01

    The assays for calcitonin receptors described focus on their use in the study of the well-established target organs for calcitonin, bone and kidney. The radioligand used in virtually all calcitonin binding studies is /sup 125/I-labelled salmon calcitonin. The lack of methionine residues in this peptide permits the use of chloramine-T for the iodination reaction. Binding assays are described for intact bone, skeletal plasma membranes, renal plasma membranes, and primary kidney cell cultures of rats. Studies on calcitonin metabolism in laboratory animals and regulation of calcitonin receptors are reviewed.

  14. Calcitonin Salmon Injection

    Science.gov (United States)

    Calcitonin salmon injection is used to treat osteoporosis in postmenopausal women. Osteoporosis is a disease that causes bones to weaken and break more easily. Calcitonin salmon injection is also used to treat Paget's disease ...

  15. Basal serum anti-müllerian hormone and antral follicle count are predictors of ovarian response for Asian women in Singapore

    Directory of Open Access Journals (Sweden)

    Lee Mee

    2014-09-01

    Conclusion: Both basal serum AMH and AFC were reliable ovarian reserve markers for predicting poor and high ovarian response to COS in Asian women. Basal AMH was the only significant predictor for clinical pregnancy outcome.

  16. Calcitonin substitution in calcitonin deficiency reduces particle-induced osteolysis

    Directory of Open Access Journals (Sweden)

    Grabellus Florian

    2011-08-01

    Full Text Available Abstract Background Periprosthetic osteolysis is a major cause of aseptic loosening in joint arthroplasty. This study investigates the impact of CT (calcitonin deficiency and CT substitution under in-vivo circumstances on particle-induced osteolysis in Calca -/- mice. Methods We used the murine calvarial osteolysis model based on ultra-high molecular weight polyethylene (UHMWPE particles in 10 C57BL/6J wild-type (WT mice and twenty Calca -/- mice. The mice were divided into six groups: WT without UHMWPE particles (Group 1, WT with UHMWPE particles (Group 2, Calca -/- mice without UHMWPE particles (Group 3, Calca -/- mice with UHMWPE particles (Group 4, Calca -/- mice without UHMWPE particles and calcitonin substitution (Group 5, and Calca -/- mice with UHMWPE particle implantation and calcitonin substitution (Group 6. Analytes were extracted from serum and urine. Bone resorption was measured by bone histomorphometry. The number of osteoclasts was determined by counting the tartrate-resistant acid phosphatase (TRACP + cells. Results Bone resorption was significantly increased in Calca -/- mice compared with their corresponding WT. The eroded surface in Calca -/- mice with particle implantation was reduced by 20.6% after CT substitution. Osteoclast numbers were significantly increased in Calca -/- mice after particle implantation. Serum OPG (osteoprotegerin increased significantly after CT substitution. Conclusions As anticipated, Calca -/- mice show extensive osteolysis compared with wild-type mice, and CT substitution reduces particle-induced osteolysis.

  17. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

    Directory of Open Access Journals (Sweden)

    Wen-Bo Wang

    2016-01-01

    Conclusions: The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls. NAFLD was an independent associated factor for ACTH levels in male IHH patients. These preliminary findings provided evidence of the relationship between basal serum ACTH and NAFLD in male IHH patients.

  18. Bivariate analysis of basal serum anti-Müllerian hormone measurements and human blastocyst development after IVF

    Directory of Open Access Journals (Sweden)

    Sills E Scott

    2011-12-01

    Full Text Available Abstract Background To report on relationships among baseline serum anti-Müllerian hormone (AMH measurements, blastocyst development and other selected embryology parameters observed in non-donor oocyte IVF cycles. Methods Pre-treatment AMH was measured in patients undergoing IVF (n = 79 and retrospectively correlated to in vitro embryo development noted during culture. Results Mean (+/- SD age for study patients in this study group was 36.3 ± 4.0 (range = 28-45 yrs, and mean (+/- SD terminal serum estradiol during IVF was 5929 +/- 4056 pmol/l. A moderate positive correlation (0.49; 95% CI 0.31 to 0.65 was noted between basal serum AMH and number of MII oocytes retrieved. Similarly, a moderate positive correlation (0.44 was observed between serum AMH and number of early cleavage-stage embryos (95% CI 0.24 to 0.61, suggesting a relationship between serum AMH and embryo development in IVF. Of note, serum AMH levels at baseline were significantly different for patients who did and did not undergo blastocyst transfer (15.6 vs. 10.9 pmol/l; p = 0.029. Conclusions While serum AMH has found increasing application as a predictor of ovarian reserve for patients prior to IVF, its roles to estimate in vitro embryo morphology and potential to advance to blastocyst stage have not been extensively investigated. These data suggest that baseline serum AMH determinations can help forecast blastocyst developmental during IVF. Serum AMH measured before treatment may assist patients, clinicians and embryologists as scheduling of embryo transfer is outlined. Additional studies are needed to confirm these correlations and to better define the role of baseline serum AMH level in the prediction of blastocyst formation.

  19. Analgesic effects of calcitonin.

    Science.gov (United States)

    Lyritis, G P; Trovas, G

    2002-05-01

    The analgesic activity of salmon calcitonin (subcutaneous or intranasal) has been demonstrated in several prospective clinical trials, in patients suffering different painful skeletal conditions, including recent nontraumatic osteoporotic vertebral fractures. The mechanism of the analgesic effect of calcitonin is not clear. It is possible that specific binding sites for salmon calcitonin exist in the brain. Another explanation is that changes in descending serotonergic modification on the sensory transmission mediated by C afferents contribute to the analgesic effects of calcitonin on pain in osteoporotic patients. From the clinical point of use, the analgesic effect of calcitonin is beneficial throughout the whole period of medical treatment of osteoporotic patients. Salmon calcitonin in a daily dose of 100 IU subcutaneously or 200 IU intranasally reduces dramatically the back pain (p salmon calcitonin effectively controls severe pain in osteoporotic patients with a recent vertebral fracture, allowing them earlier mobility in combination with a reduction of the urinary hydroxyproline excretion, and a limitation of the considerable bone loss that may occur during prolonged bed rest, make this therapeutic scheme attractive.

  20. Calcitonin Salmon Nasal Spray

    Science.gov (United States)

    ... is important that you get enough calcium and vitamin D while you are using calcitonin salmon. Your doctor ... symptoms such as crusts, dryness, redness, or swelling back pain joint pain upset stomach flushing (feeling of warmth) ...

  1. Aging-Related Correlation between Serum Sirtuin 1 Activities and Basal Metabolic Rate in Women, but not in Men

    Science.gov (United States)

    2017-01-01

    Sirtuin (SIRT) is a main regulator of metabolism and lifespan, and its importance has been implicated in the prevention against aging-related diseases. The purpose of this study was to identify the pattern of serum SIRT1 activity according to age and sex, and to investigate how serum SIRT1 activity is correlated with other metabolic parameters in Korean adults. The Biobank of Jeju National University Hospital, a member of the Korea Biobank Network, provided serum samples from 250 healthy adults. Aging- and metabolism-related factors were analyzed in serum, and the data were compared by the stratification of age and sex. Basal metabolic rate (BMR) decreased with age and was significantly lower in men in their fifties and older and in women in their forties and older compared with twenties in men and women, respectively. SIRT1 activities were altered by age and sex. Especially, women in their thirties showed the highest SIRT1 activities. Correlation analysis displayed that SIRT1 activity is positively correlated with serum triglyceride (TG) in men, and with waist circumference, systolic blood pressure, diastolic blood pressure, and serum TG in women. And, SIRT1 activity was negatively correlated with aspartate aminotransferase/alanine aminotransferase ratio in women (r = −0.183, p = 0.039). Positive correlation was observed between SIRT1 activity and BMR in women (r = 0.222, p = 0.027), but not in men. Taken together, these findings suggest the possibility that serum SIRT1 activities may be utilized as a biomarker of aging. In addition, positive correlation between SIRT1 activity and BMR in women suggests that serum SIRT1 activity may reflect energy expenditure well in human. PMID:28168178

  2. Basal serum anti-müllerian hormone and antral follicle count are predictors of ovarian response forAsian women inSingapore

    Institute of Scientific and Technical Information of China (English)

    Lee Mee Ho; Tar Choon Aw; Siew Chen Hum; Shaw Ni Lee; Stephanie Fook-Chong Man Chung; Su Ling Yu

    2014-01-01

    Objective:To determine the basal ovarian reserve markers for prediction of poor and high responses and clinical pregnancy outcome in subfertileAsian women requiring controlled ovarian stimulation(COS) treatment inSingapore.Methods:SubfertileAsian women, aged ≤40 with basal serum follicle stimulating hormone(FSH) level of ≤12IU/L, were enrolled prospectively during routine preliminary endocrine ovarian reserve assessment prior toCOS regime for intracytoplasmic sperm insemination(ICSI) cycles.Basal serum levels of the endocrine ovarian reserve markers(anti-Müllerian hormone(AMH), estradiol,FSH, luteinizing hormone), antral follicle count(AFC) and ovarian response parameters were compared between thePoor(retrieved oocytes ≤4),Normal(retrieved oocytes,5 to19) andHighResponder(retrieved oocytes ≥20) groups of women.Results:Basal serumAMH andAFC were significantly correlated to age (r =-0.213 and -0.243, respectively) and to the number of retrieved oocytes(r=0.570 and0.523, respectively)(P<0.05).Both basal serumAMH andAFC were significant discriminators of poor response(cut-off levels of ≤2.0 ng/mL and ≤12, respectively) and for high response(AMH ≥3.2 ng/mL andAFC of ≥20, respectively) toCOS.BasalAMH was the only significant predictor for clinical pregnancy outcome,ROCAUC =0.71, cut-off level of ≥3.0 ng/mL and odds ratio of 1.42.Conclusions:Both basal serumAMH andAFC were reliable ovarian reserve markers for predicting poor and high ovarian response toCOS inAsian women.BasalAMH was the only significant predictor for clinical pregnancy outcome.

  3. Renal metabolism of calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Simmons, R.E.; Hjelle, J.T.; Mahoney, C.; Deftos, L.J.; Lisker, W.; Kato, P.; Rabkin, R.

    1988-04-01

    The kidneys account for approximately two-thirds of the metabolism of calcitonin, but relatively little is known regarding the details thereof. To further characterize this process, we examined the renal handling and metabolism of human calcitonin (hCT) by the isolated perfused rat kidney. We also studied the degradation of radiolabeled salmon calcitonin (sCT) by subcellular fractions prepared from isolated rabbit proximal tubules. The total renal (organ) clearance of immunoreactive hCT by the isolated kidney was 1.96 +/- 0.18 ml/min. This was independent of the perfusate total calcium concentration from 5.5 to 10.2 mg/dl. Total renal clearance exceeded the glomerular filtration rate (GFR, 0.68 +/- 0.05 ml/min), indicating filtration-independent removal. Urinary calcitonin clearance as a fraction of GFR averaged 2.6%. Gel filtration chromatography of medium from isolated kidneys perfused with /sup 125/I-labeled sCT showed the principal degradation products to be low molecular weight forms eluting with monoiodotyrosine. Intermediate size products were not detected. In the subcellular fractionation experiments, when carried out at pH 5.0, calcitonin hydrolysis exclusively followed the activities of the lysosomal enzyme N-acetyl-beta-glucosaminidase. Typically, at pH 7.5, 42% of total degradation occurred in the region of the brush-border enzyme alanyl aminopeptidase and 29% occurred in the region of the cytosolic enzyme phosphoglucomutase. Although 9% of the calcitonin-degrading activity was associated with basolateral membrane fractions, most of this activity could be accounted for by the presence of brush-border membranes.

  4. Morning or evening administration of nasal calcitonin?

    DEFF Research Database (Denmark)

    Schlemmer, A; Ravn, Pernille; Hassager, C;

    1997-01-01

    The purpose of this study was to examine the effect of intranasal salmon calcitonin (sCT) administration (200 IE), given either in the morning (8:00) or evening (21:00), on the known circadian variation in biochemical markers of bone turnover. An open, placebo-controlled, randomized, crossover......). Serum osteocalcin (sOC) was measured by radioimmunoassay (RIA). The first 24 h study was performed without intervention. Prior to this control study the participants were randomized to either morning (8:00) or evening (21:00) sCT (200 IE). sCT administrations were given 4-5 days prior to and during...... in late afternoon. Both morning and evening administration of sCT significantly decreased the urinary excretion of CrossLaps/Cr approximately 3-6 h after administration with a subsequent rebound effect. sOC did not exhibit a significant circadian variation and was not affected by the calcitonin. The 24 h...

  5. Evaluation of Basal Serum Adrenocorticotropic Hormone and Cortisol Levels and Their Relationship with Nonalcoholic Fatty Liver Disease in Male Patients with Idiopathic Hypogonadotropic Hypogonadism

    Institute of Scientific and Technical Information of China (English)

    Wen-Bo Wang; Fei She; Li-Fang Xie; Wen-Hua Yan; Jin-Zhi Ouyang; Bao-An Wang; Hang-Yun Ma

    2016-01-01

    Background:Prolonged gonadal hormone deficiency in patients with idiopathic hypogonadotropic hypogonadism (IHH) may produce adverse effects on the endocrine homeostasis and metabolism.This study aimed to compare basal serum adrenocorticotropic hormone (ACTH) and cortisol levels between male IHH patients and healthy controls.Moreover,this study compared the basal hypothalamic-pituitary-adrenal (HPA) axis in patients with and without nonalcoholic fatty liver disease (NAFLD),and also evaluated the relationship between basal HPA axis and NAFLD in male IHH patients.Methods:This was a retrospective case-control study involving 75 Chinese male IHH patients (mean age 21.4 ± 3.8 years,range 17-30 years) and 135 healthy controls after matching for gender and age.All subjects underwent physical examination and blood testing for serum testosterone,luteinizing hormone,follicle-stimulating hormone,ACTH,and cortisol and biochemical tests.Results:Higher basal serum ACTH levels (8.25 ± 3.78 pmol/L vs.6.97 ± 2.81 pmol/L) and lower cortisol levels (366.70 ± 142.48 nmol/L vs.452.82 ± 141.53 nmol/L) were observed in male IHH patients than healthy subjects (all P < 0.05).IHH patients also showed higher metabolism parameters and higher prevalence rate of NAFLD (34.9% vs.4.4%) than the controls (all P < 0.05).Basal serum ACTH (9.91 ± 4.98 pmol/L vs.7.60 ± 2.96 pmol/L) and dehydroepiandrosterone sulfate (2123.7 ± 925.8 μg/L vs.1417.1 ± 498.4 μg/L) levels were significantly higher in IHH patients with NAFLD than those without NAFLD (all P < 0.05).We also found that basal serum ACTH levels were positively correlated with NAFLD (r =0.289,P < 0.05) and triglyceride levels (r =0.268,P < 0.05) in male IHH patients.Furthermore,NAFLD was independently associated with ACTH levels in male IHH patients by multiple linear regression analysis.Conclusions:The male IHH patients showed higher basal serum ACTH levels and lower cortisol levels than matched healthy controls.NAFLD was

  6. Calcitonin, as SMS 201-995, ameliorates the VIPoma syndrome.

    Science.gov (United States)

    Antonelli, A; Gambuzza, C; Bertoni, F; Baschieri, L

    1993-01-01

    A 72-year-old woman was referred to our hospital for diarrhea, abdominal and back pain, weight loss, low serum potassium level. Pathological findings and high circulating Vasoactive Intestinal Peptide (VIP) levels allowed us to diagnose "VIPoma syndrome". The patient underwent a treatment with SMS 201-995 with improvement of symptomatology and reduction of circulating VIP levels. After a wash-out period the patient was treated with salmon calcitonin with a net improvement of diarrhea, normalization of potassium serum level and reduction of VIP level. The symptomatology recurred after calcitonin withdrawal. These data confirm the effectiveness of SMS 201-995 in the VIPoma syndrome and suggest that calcitonin may ameliorate symptomatology and reduce circulating VIP level in patients with VIPoma tumor.

  7. Improving oral absorption of Salmon calcitonin by trimyristin lipid nanoparticles.

    Science.gov (United States)

    Martins, S; Silva, A C; Ferreira, D C; Souto, E B

    2009-02-01

    Solid lipid nanoparticles (SLN) composed of trimyristin (solid lipid) and poloxamer 407 (surfactant) were prepared by a w/o/w emulsion technique for the incorporation of Salmon calcitonin, and further explored as protein carriers for oral delivery. Trimyristin SLN showed a mean size diameter of 200 nm with an association efficiency for calcitonin of approx. 86%. The morphology of SLN was investigated by cryo-SEM and by AFM, revealing spheroid shape SLN with a smooth surface. The in vitro release of calcitonin occurred for a period of 8 h, under both gastric and intestinal simulated pH conditions, predicting suitable properties for oral administration. The pharmacological activity of the protein was evaluated following oral dosage of calcitonin-loaded SLN in rats. SLN lowered the basal blood calcium levels by up to 20% with 500 IU/kg dose sustaining hypocalcaemia over 8 h. The results indicate that incorporation of Salmon calcitonin into trimyristin SLN is a key factor for the improvement of the efficiency of such carriers for oral delivery of proteins.

  8. Calcitonin, a major gill hormone.

    OpenAIRE

    Milhaud, G; Bolis, L; Benson, A A

    1980-01-01

    Isolated salmon gills, under simulated in vivo conditions, transported calcium ion into the ambient seawater when perfused with Ringer's solution containing salmon calcitonin. Similar enhancement of phosphate efflux was observed. Calcitonin caused simultaneous decreases in perfusate flow rates. The effects act synergistically to diminish net plasma calcium concentrations.

  9. Is basal serum 17-OH progesterone a reliable parameter to predict nonclassical congenital adrenal hyperplasia in premature adrenarche?

    Science.gov (United States)

    Gönç, E Nazli; Ozön, Z Alev; Alikaşifoğlu, Ayfer; Engiz, Ozlem; Bulum, Burcu; Kandemir, Nurgün

    2011-01-01

    To determine the critical features for the diagnosis of nonclassical 21 hydroxylase deficiency (NC210HD) without performing adrenocorticotropic hormone (ACTH) test, we studied 186 cases with premature adrenarche. Clinical and laboratory features as well as basal 17-hydroxyprogesterone (17-OHP) were analyzed to determine factors important for differentiating NC21OHD. Overall, 6 patients (3.2%) had ACTH-stimulated 17-OHP > 10 ng/ml. A cutoff level of 2 ng/ml for basal 17-OHP was 66.7% sensitive and 78% specific for NC21OHD; however, a cutoff level of 1.55 ng/ml had higher sensitivity (83%) and specificity (70.6%). A cutoff of 1.55 ng/ml would lead to 31% of cases with premature adrenarche having to undergo ACTH test, and only one case would have been missed. That case had a bone age SDS > 2. Three cases out of five with a basal 17-OHP > 5 ng/ml had stimulated 17-OHP bone SDS > 2 in those with lower basal levels as a guide for carrying out an ACTH test may yield better results in the diagnosis of NC21OHD in the premature adrenarche population. A cutoff of 5 ng/ml for basal 17-OHP should not be used for diagnosis of NC21OHD.

  10. Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes.

    Science.gov (United States)

    Gunnarsson, Anders Patrik; Christensen, Rikke; Praetorius, Jeppe; Jensen, Uffe Birk

    2017-01-15

    Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization. Although CSPG4-positive basal cells express higher levels of Itgβ1 the colony-forming efficiency is slightly lower than CSPG4-negative basal cells. Sorting the directly isolated keratinocytes based on Itgβ1 did not reveal differences in colony-forming efficiency between keratinocytes expressing high or low levels of Itgβ1. However, after the first passage Itgβ1 could be used to predict colony-forming efficiency whether the culture was established from CSPG4-positive or CSPG4-negative basal cell keratinocytes. Although we were unable to detect differences in the colony-forming assay, global gene expression profiling showed that CSPG4-positive basal cell keratinocytes are distinct from CSPG4-negative basal cell keratinocytes. Our study demonstrates that it is possible to generate antibodies against trypsin-resistant epitopes of CSPG4. Our study also documents a marked change in behaviour upon cell culturing and challenges the way we assess for stemness within the human epidermal basal layer.

  11. Isolating subpopulations of human epidermal basal cells based on polyclonal serum against trypsin-resistant CSPG4 epitopes

    DEFF Research Database (Denmark)

    Gunnarsson, Anders Patrik Alexander; Christensen, Rikke; Prætorius, Jeppe

    2016-01-01

    unable to study these keratinocytes isolated directly from skin samples by flow cytometry. By choosing epitopes of CSPG4 relatively close to the cell membrane we were able to generate a polyclonal antibody that successfully detects CSPG4 on keratinocytes after trypsinization. Although CSPG4-positive......Chondroitin sulfate proteoglycan 4 (CSPG4) is highly expressed by human epidermal keratinocytes located at the tip of the dermal papilla where keratinocytes show characteristics of stem cells. However, since available antibodies to CSPG4 are directed against trypsin-sensitive epitopes we have been...... that CSPG4-positive basal cell keratinocytes are distinct from CSPG4-negative basal cell keratinocytes. Our study demonstrates that it is possible to generate antibodies against trypsin-resistant epitopes of CSPG4. Our study also documents a marked change in behaviour upon cell culturing and challenges...

  12. Medullary thyroid carcinoma in a patient with Hashimoto's thyroiditis diagnosed by calcitonin washout from a thyroid nodule.

    Science.gov (United States)

    Mousa, Umut; Gursoy, Alptekin; Ozdemir, Handan; Moray, Gokhan

    2013-07-01

    Serum calcitonin is a tumor marker used in the diagnosis and follow-up of medullary thyroid carcinoma. Calcitonin washout evaluation is a new method used for suspicious thyroid nodules and lymph nodes. Limited clinical data are present about the efficacy of this method. A 61-year-old female patient with known Hashimoto's thyroditis and an 8-mm hypoechoic nodule was presented with one previously benign fine-needle aspiration cytology (FNAC). On referral to our department, she had a moderately high-serum calcitonin level, and we repeated the FNAC that was reported as nondiagnostic. We performed FNAC for the third time together with calcitonin washout evaluation from the thyroid nodule. The FNAC was again nondiagnostic, but the calcitonin washout level from the thyroid nodule was 152.569 pg/mL. Total thyroidectomy was performed, and the diagnosis was confirmed as medullary thyroid carcinoma. Calcitonin washout evaluation may be a useful method in the differential diagnosis of patients with thyroid nodules having moderately high-serum calcitonin levels.

  13. Correlation between basal serum IGF-1 levels and functional autonomy in elderly women. (Correlación entre los niveles sericos de IGF-1 basal y autonomía funcional en las ancianas.

    Directory of Open Access Journals (Sweden)

    Rodrigo Gomes de Souza Vale

    2009-01-01

    Full Text Available Abstract The aim of the present study was to determine the degree of correlation between basal serum IGF-1 levels and functional autonomy in the performance of activities of daily living (ADL. The sample comprised 11 elderly individuals, disregarding their ADLs (age = 68.18 ± 5.19 years; body mass index (BMI = 28.89 ± 3.44 kg/m2 and not enrolled in physical exercise programs for at least 3 months. The subjects were submitted to a battery of 5 functional autonomy tests from the GDLAM protocol and blood collection to assess serum IGF-1 levels. Using Pearson’s correlation, we found a significant mean correlation coefficient (r between the 10 m walking test (10mW and IGF-1 (r = -0.690; p = 0.009 and mean correlation, but not significant between the putting on and removing a t-shirt test (PRTS and IGF-1 (r = -0.528 and between the general autonomy index (AI and IGF-1 (r = -0.417. The correlation was low in the remaining tests, but inversed. This suggests that the decline in IGF-1 with age may decrease ADL performance in the elderly. Key words: Serum IGF-1; ADL; elderly. Resumen El objetivo del presente estudio fue comprobar el nivel de la correlación entre los niveles de serum basal de IGF-1 y la autonomía funcional para la realización de las actividades de la vida diaria en personas mayores (edad = 68,18 ± 5,19 años; índice de la masa corporal, IMC = 28,89 ± 3,44 kg/m2, no participantes de los programas de ejercicios físico desde hace un mínimo de 3 meses. Los sujetos fueron sometidos a una batería de 5 tareas de autonomía funcional del protocolo GDLAM y un análisis de sangre para evaluar los niveles de serum de IGF-1. A través de la correlación de Pearson se comprobó la existencia de un coeficiente de la correlación (r medio y significativo entre el examen de la marcha 10m (C10m y el IGF-1 (r = -0,690; p=0,009 y la correlación media, pero no significativa ,entre el test de vestirse y quitarse una camiseta (VTC y el IGF-1 (r= -0

  14. The Comparison of Immune Turbidimetric Method and Immunofluorescence Quantitative Analysis Method in the Measurement of Serum ;Calcitonin Original%免疫比浊法与免疫荧光定量分析法测量血清降钙素原比较

    Institute of Scientific and Technical Information of China (English)

    李秉忠

    2015-01-01

    Objective:To compare the results of the immune turbidimetric method and immunofluorescence quantitative analysis method in the measurement of serum calcitonin original.Method:202 cases of different concentrations of serum calcitonin were selected,they were all checked by zhejiang ransom biotechnology co.,LTD.Production of latex enhanced immune turbidimetry and guangzhou Wan Fu biological immunofluorescence quantitative analysis production company at the same time,the results and data statistics were analyzed.Result:the concentration values of the two methods in elevated group,the low risk group,negative group had no statistically significant(P>0.05);the concentration values of the two methods in highly group and moderately elevated group concentration had significant difference(P0.05).Conclusion:Immune turbidimetry and immunofluorescence quantitative analysis can be used for clinical serum calcitonin original detection,and immunofluorescence operation is more simple.%目的:比较免疫比浊法和免疫荧光定量分析法在测量血清降钙素原时的结果。方法:选取把在笔者所在医院进行降钙素检测的202例浓度不同的血清降钙素,分别用浙江兰森生物科技有限公司生产的乳胶增强免疫比浊法和广州万孚生物公司生产的免疫荧光定量分析法同时进行监测,并对结果和数据进行统计学的分析。结果:经比较,这两种方法在轻度升高组、低风险组、阴性组的浓度值方面比较,差异无统计学意义(P>0.05);在高度和中度升高组的浓度值方面比较,差异有统计学意义(P0.05)。结论:免疫比浊法和免疫荧光定量分析法均可用于临床血清降钙素原的检测,且免疫荧光法操作比较简便。

  15. A Core MYC Gene Expression Signature Is Prominent in Basal-Like Breast Cancer but Only Partially Overlaps the Core Serum Response

    Science.gov (United States)

    Chandriani, Sanjay; Frengen, Eirik; Cowling, Victoria H.; Pendergrass, Sarah A.; Perou, Charles M.; Whitfield, Michael L.; Cole, Michael D.

    2009-01-01

    Background The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear. Methodology/Principal Findings Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNΔMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNΔMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a ‘Core MYC Signature’ and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples. Conclusions/Significance The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes. PMID:19690609

  16. A core MYC gene expression signature is prominent in basal-like breast cancer but only partially overlaps the core serum response.

    Directory of Open Access Journals (Sweden)

    Sanjay Chandriani

    Full Text Available BACKGROUND: The MYC oncogene contributes to induction and growth of many cancers but the full spectrum of the MYC transcriptional response remains unclear. METHODOLOGY/PRINCIPAL FINDINGS: Using microarrays, we conducted a detailed kinetic study of genes that respond to MYCN or MYCNDeltaMBII induction in primary human fibroblasts. In parallel, we determined the response to steady state overexpression of MYCN and MYCNDeltaMBII in the same cell type. An overlapping set of 398 genes from the two protocols was designated a 'Core MYC Signature' and used for further analysis. Comparison of the Core MYC Signature to a published study of the genes induced by serum stimulation revealed that only 7.4% of the Core MYC Signature genes are in the Core Serum Response and display similar expression changes to both MYC and serum. Furthermore, more than 50% of the Core MYC Signature genes were not influenced by serum stimulation. In contrast, comparison to a panel of breast cancers revealed a strong concordance in gene expression between the Core MYC Signature and the basal-like breast tumor subtype, which is a subtype with poor prognosis. This concordance was supported by the higher average level of MYC expression in the same tumor samples. CONCLUSIONS/SIGNIFICANCE: The Core MYC Signature has clinical relevance as this profile can be used to deduce an underlying genetic program that is likely to contribute to a clinical phenotype. Therefore, the presence of the Core MYC Signature may predict clinical responsiveness to therapeutics that are designed to disrupt MYC-mediated phenotypes.

  17. Calcitonin treatment in osteoectasia with hyperphosphatasia (juvenile Paget's disease): radiographic changes after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Tueysuez, B. [Div. of Genetics and Teratology, Univ. of Istanbul (Turkey); Serencebey, Istanbul (Turkey); Mercimek, S.; Uenguer, S. [Dept. of Paediatrics, Univ. of Istanbul (Turkey); Deniz, M. [Dept. of Paediatrics, Haseki Hospital, Istanbul (Turkey)

    1999-11-01

    Osteoectasia with hyperphosphatasia is a rare skeletal disorder, characterised by demineralisation and expansion of tubular bones and elevated serum alkaline phosphatase. We present a girl diagnosed as having osteoectasia with hyperphosphatasia who had swelling of phalanges of both hands and motor retardation. She was treated with synthetic human calcitonin. Clinical and radiological findings showed remarkable improvement after 2 years' treatment. (orig.)

  18. Effect of Acupuncture on Calcitonin in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    ZHAORong; LIUChuyu; LVGuangrong; CAOJianming; LIQingyun

    2003-01-01

    Objective To Explore the mechanism of the acupuncture on posanenopausal osteoporo-sis.Method One hundred Wistar female rats(6 month- old)were randomly divided into two groups: O-variectomized group and sham - operated group. After 3 months of operation, three rats were chosen tomeasure the bone histomorphometric indexes. Then the ovariectomized rats were distributed randomly to acupuncture group and yigaining group and normal saline group and control 2 group, the rats were respec-tively treated by acupuncture and yigaining and normal saline. After the treatment for three course, all rats were collected blood from the ateria femoralis, the levels of calcitonin were measured by IRMA. the bone histomorphometric indexes and C - cell in thyroid follicle were detected. Results The levels of calcitonin of acupuncture group were increasing significantly comparing with the yigaining group and the normal saline group and the control 2 group ( p < 0.05), but there were no evident difference in the levels of cal-citonin between the acupuncture group and the sham - operated group. The mean trabecular bone width and the tmbecuhar bone volume % of acupuncture group were increasing more than that of the normal saline group and the control 2 group(p < 0.05) ;the mean marrow cavity width and the marrow cavity vol-ume % were derreasing more than that of the nomal saline group and the control 2 group( P < 0.05) ; the number of C - cell in thyroid follicle of the acupuncture group were increasing more than that of the other groups except the sham - operated group. Conclusion Acupuncture can effectively treat the post-menopausal osteoporosis by strengthening the ability of the C - cell in thyroid follicle which can improve the levels of calcitonin in serum.

  19. Skeletal blood flow in Paget's disease of bone and its response to calcitonin therapy.

    Science.gov (United States)

    Wootton, R; Reeve, J; Spellacy, E; Tellez-Yudilevich, M

    1978-01-01

    1. Blood flow to the skeleton was measured by the 18F clearance method of Wooton, Reeve & Veall (1976) in 24 patients with untreated Paget's disease. In every patient but one, resting skeletal blood flow was increased. There was a significant positive correlation between skeletal blood flow and serum alkaline phosphatase and between skeletal blood flow and urinary total hydroxyproline excretion. 2. Fourteen patients were re-studied after they had received short-term (7 days or less) or long-term (7 weeks or more) calcitonin. Skeletal blood flow, alkaline phosphatase and urinary hydroxy-proline excretion fell towards normal in every case. There was some evidence from the short-term studies that calcitonin produced a more rapid fall in skeletal blood flow than in alkaline phosphatase. 3. Glomerular filtration rate appeared to increase transiently in response to calcitonin.

  20. Physiological and clinical studies of calcium-regulating hormones calcitonin and parathyroid hormone-related protein

    OpenAIRE

    1997-01-01

    The present studies were performed to elucidate several physiological and clinical questions of calcitonin (CT) and parathyroid hormone-related protein (PTHrP) such as: a) Does age influence the basal and calcium-stimulated levels and circulating molecular forms of CT in healthy females? b) Are osteoporotic patients lacking circulating monomeric CT? c) How is salmon CT (sCT) absorbed and cleared during treatment of diseases? d) Is there any effect of acute physical activity ...

  1. Calcitonin

    Science.gov (United States)

    ... tumors Chronic renal failure Zollinger-Ellison syndrome Pernicious anemia ^ Back to top Proudly sponsored by ... Learn more about ... Understanding Your Tests Inside the Lab In the News Article Index About This Site Send Us Your Comments For ...

  2. Effect of calcium carbonate combined with calcitonin on hypercalcemia in hemodialysis patients.

    Science.gov (United States)

    Wei, Yong; Kong, Xiang Lei; Li, Wen Bin; Wang, Zun Song

    2014-12-01

    This short-term study assessed the efficacy and safety of calcium carbonate combined with calcitonin in the treatment of hypercalcemia in hemodialysis patients. Patients (n=64) on hemodialysis for chronic kidney disease for more than 6 months were included based on total serum calcium more than 10.5 mg/dL. All patients were randomized (1:1) to receive calcium carbonate combined with calcitonin (Group I) or lanthanum carbonate (Group II) for 12 weeks. Blood levels of calcium, phosphorus and intact parathyroid hormone (iPTH) were measured every month, bone mass density (BMD) and coronary artery calcium scores (CACS) were measured at 3 months. During the study period, serum calcium decreased from 10.72 ± 0.39 to 10.09 ± 0.28 mg/dL (P carbonate combined with calcitonin and lanthanum carbonate were equally effective in the suppression of hypercalcemia in hemodialysis patients. There were no serious treatment-related adverse events in treatment with calcium carbonate combined with calcitonin.

  3. Effects of calcitonin on the osteoporotic skeleton

    Energy Technology Data Exchange (ETDEWEB)

    Agrawal, R.; Wallach, S.; Cohn, S.; Wu, T.; Tessier, M.; Verch, R.; Hussain, M.; Zanzi, I.

    1981-01-01

    Synthetic salmon calcitonin at a dose of 100 MRC units daily was administered to nine biopsy-proven osteoporotic men, aged 50 years and older, for one to two years. Two additional groups of men with comparable degrees of osteoporosis received either multivitamins alone or multivitamins plus a calcium supplement. The group treated with salmon calcitonin increased their total body calcium by 3% at the end of two years, whereas no change was seen in the other two groups. This result was not statistically significant because of dispersion of the data. There was also no significant changes in bone mineral content of the distal forearm. Four of the nine men treated with calcitonin had increases in total body calcium, which exceeded the reproducibility of the in vivo neutron activation method by 2 SD (SD +- 1.1%). The mean increase in total body calcium in these four patients was 8% compared to a mean decrease of 2 to 4% in the remainder. New vertebral compression and/or collapse was significantly less frequent in the group treated with calcitonin (1.0 +- 0.6 per patient) compared to the other two groups (2.4 +- 0.8 and 2.0 +- 0.6 per patient). These data support the thesis that calcitonin can increase skeletal mass in selected osteoporotic patients and justify further studies to detect responsive patients and to amplify the effect of calcitonin in such patients. 5 references.

  4. Effect of Acupuncture on Calcitonin in Ovariectomized Rats

    Institute of Scientific and Technical Information of China (English)

    ZHAO Rong; LIU Chuyu; LV Guangrong; CAO Jianming; LI Qingyun

    2003-01-01

    Objective To Explore the mechanism of the acupuncture on postmenopausal osteoporosis. Method One hundred Wistar female rats(6 month-old)were randomly divided into two groups:Ovariectomized group and sham - operated group. After 3 months of operation, three rats were chosen tomeasure the bone histomorphometric indexes. Then the ovariectomized rats were distributed randomly toacupuncture group and yigaining group and normal saline group and control 2 group,the rots were respec-tively treated by acupuncture and yigaining and normal saline. After the treatment for three course, all ratswere collected blood from the ateria femoralis, the levels of calcitonin were measured by IRMA. The bonehistomorphometric indexes and C - cell in thyroid follicle were detected. Results The levels of calcitoninof acupuncture group were increasing significantly comparing with the yigaining group and the normalsaline group and the control 2 group (p < 0.05),but there were no evident difference in the levels of cal-citonin between the acupuncture group and the sham - operated group. The mean trabecular bone widthand the trabecular bone volume % of acupuncture group were increasing more than that of the normalsaline group and the control 2 group(p < 0.05) ;the mean marrow cavity width and the marrow cavity volume % were derreasing more than that of the nomal saline group and the control 2 group(P < 0.05) ;thenumber of C - cell in thyroid follicle of the acupuncture group were increasing more than that of the othergroups except the sham - operated group. Conclusion Acupuncture can effectively treat the post-menopausal osteoporosis by strengthening the ability of the C - cell in thyroid follicle which can improvethe levels of calcitonin in serum.

  5. The calcitonin gene is expressed in salmon gills.

    OpenAIRE

    Martial, K; Maubras, L; Taboulet, J; Jullienne, A; M. Berry; Milhaud, G; Benson, A A; Moukhtar, M S; Cressent, M

    1994-01-01

    Calcitonin is an important physiological regulator of salmon gills. Although the calcitonin receptor was found in salmon gills, the critical question concerning the source of the hormone remained unanswered. In this communication, evidence is presented for expression of calcitonin mRNA and its encoded peptide in gills of the pink salmon, Oncorhynchus gorbuscha. The expression of calcitonin gene transcripts was demonstrated by reverse transcription-polymerase chain reaction, Southern hybridiza...

  6. Salmon calcitonin in prevention of osteoporosis in maintenance dialysis patients

    Institute of Scientific and Technical Information of China (English)

    WANG Shi-xiang; LI Han

    2008-01-01

    Background Renal osteodystrophy is one of the commonest complications of chronic renal failure. It may have a severe impact on the quality of life of patients on maintenance dialysis therapy. Besides post-menopausal women and elderly people, the dialysis patients are another high risk group. But at present, there is no research on how to prevent osteoporosis in maintenance dialysis patients. This study was conducted to observe the bone density of maintenance dialysis patients and to evaluate the clinical outcomes and safety of different administration dosage of salmon calcitonin to prevent osteoporosis in maintenance dialysis patients.Methods One hundred and forty-eight patients on maintenance dialysis were involved in the 12-month, randomized, controlled trial. Fifty patients (experiment Ⅰ group) received subcutaneous injection of salmon calcitonin (50 U) three times a week for 12 months. Fifty patients (experiment Ⅱ group) received subcutaneous injection of salmon calcitonin (100 U) three times a week for 12 months. At the same time, both of them received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 μg qn for 12 months. The control group only received oral calcium carbonate 1500 mg tid and rocaltrol 0.25 μg qn for 12 months. The levels of bone mass density (BMD) of the lumbar spine and femoral neck, serum intact parathyroid hormone (iPTH), osteocatcin (OC), calcium, phosphorus, alkaline phosphatase (ALP) were assessed at baseline and then again after 3, 6 and 12 months of treatment.Results The values of BMD at the lumbar spine and femoral neck before the treatment were not significantly different from those 3, 6, and 12 months after the treatment in trial groups I and II (all P >0.05) and there were no significant differences in the BMD values at different time points between trial groups I and I1. In the control group, the BMD values at the lumbar spine and femoral neck 3, 6, and 12 months after the beginning of trial were significantly lower than

  7. Components of the RANK/RANKL/OPG system, IL-6, IL-8, IL-16, MMP-2, and calcitonin in the sera of patients with bone tumors.

    Science.gov (United States)

    Kushlinskii, N E; Timofeev, Yu S; Solov'ev, Yu N; Gerstein, E S; Lyubimova, N V; Bulycheva, I V

    2014-08-01

    Serum levels of sRANKL, RANK, OPG, IL-8, IL-6, IL-16, MMP-2, and calcitonin were measured by ELISA in patients with malignant, borderline, and benign bone tumors and in healthy individuals (control). Serum levels of RANK, OPG, IL-8, IL-6, and the OPG/sRANKL ratio were significantly higher, while the level of MMP-2 was significantly lower in patients with bone tumors than in controls. Serum concentration of IL-16 in osteosarcoma patients was significantly lower than in chondrosarcoma patients. No significant differences between bone sarcomas of different differentiation were detected for any of the studied markers. Calcitonin level depended on the tumor location and type.

  8. Evaluation of the analgesic effect of salmon calcitonin in metastatic bone pain

    Directory of Open Access Journals (Sweden)

    Mishra Seema

    2003-01-01

    Full Text Available Aim: To evaluate the efficacy of calcitonin in controlling metastatic bone pain. Materials and methods: Patients with bone metastases, with a numerical pain score greater than 4 wererandomized to receive calcitonin 200 IU subcutaneously 6 hourly for 48 hours (n= 10 or normal saline placebo (n = 10 . The parameters measured were the 11-point numerical pain score, ECOG functional capacity score, morphine consumption in 24 hours, duration of pain in 24 hours and subjective assessment of efficacy of treatment by a blinded investigator. Results: There was a statistically significant decrease in pain score at 48 hours (2 vs 6 and 7 days (3 vs 6 in the calcitonin arm as compared to the control arm. The reduction in duration of pain (3 vs 13 and improvement in ECOG (1.5 vs 2.5 score were also statistically significant. Adverse effects were nausea in 5 patients and vomiting in 3 patients on the day of calcitonin administration. This was controlled with antiemetics. There was no significant change in serum calcium level in either group.

  9. Spinal-cord syndrome due to non-compressive Paget's disease of bone: a spinal-artery steal phenomenon reversible with calcitonin.

    Science.gov (United States)

    Herzberg, L; Bayliss, E

    1980-07-05

    A 76-year-old man had progressive low back pain, leg weakness, and sensory loss. Radiology showed changes consistent with wide-spread Paget's disease, but no cord compression or involvement of nerve roots was detected by myelography or computerised axial tomography. His symptoms were relieved within 12 days of starting 100 MRC units of subcutaneous salmon calcitonin and recurred when calcitonin was discontinued for 5 days. The improvement continued on calcitonin treatment for 1 year, with falls in serum alkaline phosphatase and urinary hydroxyproline excretion. It is suggested that calcitonin treatment, in reducing the abnormally high metabolic activity of the diseased bone, and hence its vascular perfusion, allows more blood to reach the spinal cord.

  10. 腹膜透析并发感染性腹膜炎患者血清降钙素原检测的临床意义%Peritoneal Dialysis Concurrent Infectious Peritonitis in Patients with Serum Calcitonin Original Clinical Significance of Detection

    Institute of Scientific and Technical Information of China (English)

    宋新宇

    2016-01-01

    目的:探讨分析腹膜透析并发感染性腹膜炎患者血清降钙素原检测的临床意义。方法选取我院2013年1月至2015年7月期间腹膜透析中心24例接受腹膜透析的患者作为研究分析对象,同时,所选24例患者均接受电化学发光免疫分析法进行检测,依据检测结果将其分为非腹膜炎组(12例)、腹膜炎组(12例),并选取同时期到我院体检健康者12例作为对照组,三组研究对象均接受血清降钙素原检验,比较三组研究对象检测结果。结果非腹膜炎组和腹膜炎组比较血清 PCT 指数,腹膜炎组明显高于非腹膜炎组,组间数据有统计学意义(P0.05);非腹膜炎组和腹膜炎组比较,血清 CRP 指数明显升高(P0.05)。结论腹膜透析并发感染性腹膜炎患者的血清降钙素原检测指数有明显升高趋势,临床中,对腹膜透析并发感染性腹膜炎疾病的判定有一定作用,同时也可用来评价临床治疗状况。%Objective To investigate the clinical significance of serum levels of calcitonin in patients with peritoneal dialysis complicated with infection. Methods 2013 January to July 2015 during peritoneal dialysis center 24 cases accepted peritoneal dialysis patients as the analysis object, at the same time, the selected 24 patients underwent electrochemical luminescence immunoassay was used to detect the. Based on the test results will be classified as non peritonitis group (12 cases), the peritonitis group (12 cases), and select the same period in our hospital for a medical examination of the health and 12 cases as control group, three groups of subjects were treated with serum procalcitonin test, were compared among the three groups of research object detection results. Results The peritonitis group and peritonitis group serum PCT index, peritonitis group was significantly higher than that in non peritonitis group was statistically significant between two groups of data

  11. The Effect of Continous or Intermittent Calcitonin in the Treatment of Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-03-01

    Full Text Available The aim of this study was to compare the efficacy of continuous and intermittent salmon calcitonin in the treatment of postmenopausal osteoporosis. Sixty-eight women with postmenopausal osteoporosis were randomized to 2 treatment groups. The first group consisting of 33 patients received nasal salmon calcitonin 200 IU/day. Thirty-five patients in the second group were treated with 200 IU of nasal SCT daily for 5 days with a subsequent pause of 2 days. All received a daily supplement of 1000 mg calcium. Both treatment regimen were applied for 12 months. The effect of nasal calcitonin on bone mineral density (BMDwas investigated by DEXA. Serum ALP, Ca and P levels and urinary Ca excretion were assessed before the treatment and at the end of 12 months. Serum ALP levels decreased mildly, but in a statistically significant manner in both groups ( p 0.05. There was a significant increase above baseline in the BMD of the lumbar spine, trochanteric region and Ward’s triangle in both groups (p 0.05. This study indicates that both continuous and intermittent SCT at a dosage of 200 IU/day are effective in the treatment of postmenopausal osteoporosis .

  12. A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin.

    Science.gov (United States)

    Karsdal, Morten A; Byrjalsen, Inger; Henriksen, Kim; Riis, Bente J; Christiansen, Claus

    2009-02-01

    The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 years old, randomly assigned to a comparison of dosing with ssCT (n = 12) or rsCT (n = 24) given in the morning at 08:00. Study parameters were plasma CT levels measured up to 2 hours postdose and changes in the bone resorption marker serum CTX-I and the cartilage degradation marker urine CTX-II measured up to 4 hours postdose. For both formulations, peak plasma concentrations were obtained 15 minutes after dosage, and no statistically significant differences in the uptake of CT were observed. Measurement of bone resorption and cartilage degradation markers displayed comparable responses, with AUCs of relative change of serum CTX-I of -250% x hours and relative change of urine CTX-II of -180% x hours during the 4-hour observation period. In conclusion, oral synthetic and recombinant calcitonin displayed comparable pharmacodynamic and kinetic properties.

  13. Whisky: a new provacative test for calcitonin secretion.

    Science.gov (United States)

    Dymling, J F; Ljungberg, O; Hillyard, C J; Greenberg, P B; Evans, I M; MacIntyre, I

    1976-07-01

    Oral whisky is a potent stimulus of calcitonin secretion. Peak increments of immunoreactive calcitonin are observed within 15 min after the ingestion of 50 ml of whisky; the magnitude of the response is similar to that observed during a four-hour calcium infusion. This procedure has several advantages over standard methods of stimulating calcitonin release in patients at risk of developing medullary carcinoma of the thyroid, and this is shown by a study in a large family with familial chromaffinomatosis.

  14. Elucidation of the nucleotide sequence of chicken calcitonin mRNA: direct evidence for the expression of a lower vertebrate calcitonin-like gene in man and rat.

    OpenAIRE

    Lasmoles, F.; Jullienne, A; Day, F; Minvielle, S.; Milhaud, G; Moukhtar, M S

    1985-01-01

    Calcitonin shows considerable divergence in amino acid sequence between lower vertebrates and higher vertebrates. Immunoreactive salmon-like calcitonin molecules are present in the thyroid of man and rat. Elucidation of the almost complete sequence of chicken calcitonin mRNA revealed that the calcitonin precursor in chickens had the same organisation as in higher vertebrates (man and rat) but showed considerable differences in amino acid sequence. cDNA probes specific for chicken calcitonin m...

  15. Basal Cell Carcinoma

    Science.gov (United States)

    ... Kids’ zone Video library Find a dermatologist Basal cell carcinoma Overview Basal cell carcinoma: This skin cancer ... that has received years of sun exposure. Basal cell carcinoma: Overview Basal cell carcinoma (BCC) is the ...

  16. In vivo iontophoretic delivery of salmon calcitonin across microporated skin.

    Science.gov (United States)

    Vemulapalli, Viswatej; Bai, Yun; Kalluri, Haripriya; Herwadkar, Anushree; Kim, Hyun; Davis, Shawn P; Friden, Phil M; Banga, Ajay K

    2012-08-01

    The purpose of this study was to determine the effect of microneedle (MN) technology and its combination with iontophoresis (ITP) on the in vivo transdermal delivery of salmon calcitonin (sCT). Maltose MNs (500 µm) were used to porate skin prior to application of the drug, with or without ITP. Micropores created by maltose MNs were characterized by histological sectioning and calcein imaging studies, which indicated uniformity of the created micropores. In vivo studies were performed in hairless rats to assess the degree of enhancement achieved by ITP (0.2 mA/cm² for 1 h), MNs (81 MNs), and their combination. In vivo studies indicate a serum maximal concentration of 0.61 ± 0.42 ng/mL, 1.79 ± 0.72 ng/mL, and 5.51 ± 0.32 ng/mL for ITP, MNs, and combination treatment, respectively. MN treatment alone increased serum concentration 2.5-fold and the combination treatment increased the concentration ninefold as compared with iontophoretic treatment alone. Combination treatment of ITP and MNs resulted in the highest delivery of sCT and therapeutic levels were achieved within 5 min of administration.

  17. Role of calcitonin in management of musculoskeletal pain

    Directory of Open Access Journals (Sweden)

    Lars Arendt-Nielsen

    2009-12-01

    Full Text Available Calcitonin was discovered more than 40 years ago and the scientific community continues to debate the primary and secondary pharmacological actions of calcitonin. Presently calcitonin is accepted by agencies only for treatment of osteoporosis, but many studies have indicated an effect on pain in many different experimental settings both pre-clinically and clinically. The effects of calcitonin on clinical pain conditions have received increasing attention in the past decades, although a consensus on mode of action and potential indications still has to be reached. Several key advances in the pain field may enable a deeper understanding of the putative analgesic effects of calcitonin. Most studies have focused on the effect of calcitonin on musculoskeletal pain problems. Ample lines of independent evidence suggest that calcitonin exerts putative analgesic effects. Well-designed clinical trials, particularly in the field of musculoskeletal pain, are needed to validate fragmented evidence of analgesic actions. This in combination with advanced mechanism-based pain assessment tools can provide new insight into the role of calcitonin, alone or in combination with other compounds, in management of pain.

  18. Hepatitis B virus basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

    Science.gov (United States)

    Yan, Chun-Hui; Zhao, Cheng-Yu; Ding, Hai; Peng, Ya-Qin; Jin, Peng-Yuan; Yan, Ling; Zhuang, Hui; Li, Tong

    2012-11-01

    The present study was aimed to obtain baseline information of basal core promoter A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192 HBeAg-positive chronically-infected Chinese patients, who were potential candidates for antiviral treatment. The detection of these mutations (including minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity for minor mutant subpopulations identification was confirmed by clone sequencing. Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV identified by routine tests in our laboratory. The A1762T/G1764A or G1896A mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125, 61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs. 20.22% (18/89), Pgenotypes. The emergence of A1762T/G1764A mutations was also found to be associated with an older age, an elevated ALT/AST level, and a lower HBsAg level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36), Pgenotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

  19. Calcitonin-like diuretic hormones in insects.

    Science.gov (United States)

    Zandawala, Meet

    2012-10-01

    Insect neuropeptides control various biological processes including growth, development, homeostasis and reproduction. The calcitonin-like diuretic hormone (CT/DH) is one such neuropeptide that has been shown to affect salt and water transport by Malpighian tubules of several insects. With an increase in the number of sequenced insect genomes, CT/DHs have been predicted in several insect species, making it easier to characterize the gene encoding this hormone and determine its function in the species in question. This mini review summarizes the current knowledge on insect CT/DHs, focusing on mRNA and peptide structures, distribution patterns, physiological roles, and receptors in insects.

  20. Pulp response after calcitonin treatment of direct exposures in the dog.

    Science.gov (United States)

    Cullum, D R; Kline, L W

    1985-08-01

    The hypocalcemic hormone, calcitonin, was used in directly pulp-capped teeth to determine whether or not calcitonin promoted healing. Two dogs were used. Twelve teeth received the calcitonin; nine control teeth were prepared, and five were treated with calcium hydroxide. Calcitonin did not increase either the rate of healing or the amount of secondary dentin formed. Calcitonin reduced the degree of inflammation in the treated tooth pulps.

  1. Delivery of salmon calcitonin using a microneedle patch.

    Science.gov (United States)

    Tas, Cetin; Mansoor, Saffar; Kalluri, Haripriya; Zarnitsyn, Vladimir G; Choi, Seong-O; Banga, Ajay K; Prausnitz, Mark R

    2012-02-28

    Peptides and polypeptides have important pharmacological properties but only a limited number have been exploited as therapeutics because of problems related to their delivery. Most of these drugs require a parenteral delivery system which introduces the problems of pain, possible infection, and expertise required to carry out an injection. The aim of this study was to develop a transdermal patch containing microneedles (MNs) coated with a peptide drug, salmon calcitonin (sCT), as an alternative to traditional subcutaneous and nasal delivery routes. Quantitative analysis of sCT after coating and drying onto microneedles was performed with a validated HPLC method. In vivo studies were carried out on hairless rats and serum levels of sCT were determined by ELISA. The AUC value of MNs coated with a trehalose-containing formulation (250 ± 83 ng/mL min) was not significantly different as compared to subcutaneous injections (403 ± 253 ng/mL min), but approximately 13 times higher than nasal administration (18.4 ± 14.5 ng/mL min). T(max) (7.5 ± 5 min) values for MN mediated administration were 50% shorter than subcutaneous injections (15 min), possibly due to rapid sCT dissolution and absorption by dermal capillaries. These results suggest that with further optimization of coating formulations, microneedles may enable administration of sCT and other peptides without the need for hypodermic injections.

  2. Rapid calcitonin response to experimental hypercalcemia in healthy horses.

    Science.gov (United States)

    Rourke, K M; Kohn, C W; Levine, A L; Rosol, T J; Toribio, R E

    2009-05-01

    Calcium has important physiological functions, and disorders of calcium homeostasis are frequent in horses. We have made important progress understanding equine calcium homeostasis; however, limited information on equine calcitonin (CT) is available, in part because of the lack of validated CT assays. To determine the CT response to high ionized calcium (Ca(2+)) concentrations in healthy horses, we induced hypercalcemia in 10 healthy horses using a calcium gluconate 23% solution (5mg/kg; 120 mL/500 kg horse) infused over 4 min. Four horses were infused with 120 mL of 0.9% NaCl and used as controls. We validated a human-specific CT radioimmunoassay for use in horses. Serum Ca(2+) concentrations increased from 6.2+/-0.3mg/dL to 9.9+/-0.5mg/dL (4 min; Pequine thyroid gland C-cell responds quickly to changes in extracellular Ca(2+) concentrations by secreting large quantities of CT into the systemic circulation, indicating that CT is important in equine calcium homeostasis. The human CT radioimmunoassay can be used to measure changes in equine CT.

  3. Ultimobranchial gland of freshwater catfish, Heteropneustes fossilis, in response to calcitonin administration

    Directory of Open Access Journals (Sweden)

    Ajai K. Srivastav

    2009-12-01

    Full Text Available The absence o!!f a hypocalcemic effect of calcitonin (CT in fishes has been suggested due to exceedingly high plasma levels of CT; the fish may be saturated with respect of circulating CT and therefore unable to respond to exogenously administered CT. Earlier it has been suggested that a hypocalcemic action of injected CT may be obscured by changes in the release of endogenous CT and other calcium regulating hormones. In this study we have used artificial freshwater, calcium-deficient freshwater and calcium-rich freshwater and injected the fish with CT. The aim behind selecting these media were (i in calcium-deficient medium there would be reduced circulating levels of CT, (ii in calcium-rich medium there would be diminished secretion of prolactin (this hormone is hypercalcemic in fish, and (iii by keeping the fish in calcium-rich medium we can test the antihypercalcemic action of CT. Moreover, the present study would reveal the changes in the ultimobranchial gland (UBG after keeping the fish in all the above three media and/or injecting the fish with CT. Freshwater catfish, Heteropneustes fossilis, were administered intraperitoneally daily with vehicle or 0.5 U/100g body wt of salmon calcitonin (CT and kept in artificial freshwater, calcium-rich freshwater and calcium-deficient freshwater for 10 days. Blood samples were collected on 1, 3, 5, and 10 days following the treatment and analyzed for serum calcium levels. The ultimobranchial gland (UBG was also fixed for histological studies on these intervals. In artificial freshwater there was no change in the serum calcium levels of calcitonin-injected fish. The ultimobranchial gland of calcitonin-injected fish exhibited a progressive decrease in the nuclear volume from day 5 onwards. On day 10 vacuolization in the gland was also noticed. In vehicle-injected fish (control kept in calcium-rich freshwater hypercalcemia has been noticed which persists till the end of the experiment. In calcitonin

  4. Salmon calcitonin: a review of current and future therapeutic indications.

    Science.gov (United States)

    Chesnut, C H; Azria, M; Silverman, S; Engelhardt, M; Olson, M; Mindeholm, L

    2008-04-01

    Salmon calcitonin, available as a therapeutic agent for more than 30 years, demonstrates clinical utility in the treatment of such metabolic bone diseases as osteoporosis and Paget's disease, and potentially in the treatment of osteoarthritis. This review considers the physiology and pharmacology of salmon calcitonin, the evidence based research demonstrating efficacy and safety of this medication in postmenopausal osteoporosis with potentially an effect on bone quality to explain its abilities to reduce the risk of spine fracture, the development of an oral salmon calcitonin preparation, and the therapeutic rationale for this preparation's chondroprotective effect in osteoarthritis.

  5. Salmon calcitonin in the prevention and treatment of osteoporosis.

    Science.gov (United States)

    Avioli, L V

    1997-04-01

    The principal calcitonins used therapeutically are porcine, human (synthetic), salmon (synthetic), and eel. Of these substances, salmon calcitonin is the most potent (Reginster 1991). Injectable forms of salmon calcitonin were first indicated for use in the treatment of Paget's disease in the United States and later received an indication for use in the treatment of postmenopausal osteoporosis. The injectable [intramuscular (IM) or subcutaneous (SC)] formulation of salmon calcitonin, however, has been associated with a high rate of noncompliance in elderly patients. The recently approved nasal-spray formulation has ameliorated the difficulties inherent in parenteral administration and is considered a suitable option as an alternative therapy in patients who are not appropriate candidates for estrogen replacement therapy. (Trends Endocrinol Metab 1997;8:89-92). (c) 1997, Elsevier Science Inc.

  6. Inhibitory effect of calcitonin on pure human pancreatic secretion.

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    Tanaka,Juntaro

    1989-06-01

    Full Text Available The inhibitory effect of calcitonin on human pancreatic secretion was evaluated to examine whether the different results reported earlier between humans, cats and dogs can be ascribed to the different sensitivity of these species to calcitonin, as suggested by some investigators. Pancreatic juice was obtained by endoscopic cannulation of the pancreatic duct from 11 patients with relapsing pancreatitis during intravenous infusion of secretin (1 U/kg/h plus caerulein (0.04 microgram/kg/h. After steady secretion was attained 20 min after the beginning of collection, five 2-min fractions were obtained before, and ten 2-min fractions were obtained after intravenous infusion of calcitonin (1 IU/kg/h. The pre- and post-calcitonin fractions from each patient were compared by Student's t-test. Calcitonin inhibited the secretory volume (26.8 to 65.6% and bicarbonate secretion (21.4 to 62.0% in 8 patients, and amylase (48.4 to 89.5% and lipase secretion (47.4 to 90.5% in all patients. The present studies reconfirmed that prominent inhibition of enzyme secretion occurs in humans. A new finding was that significant inhibition of the secretory volume and bicarbonate secretion occurs in humans. The inhibitory effects of calcitonin in humans did not appear to differ from those in cats and dogs, when evaluated similarly with the use of pure pancreatic juice.

  7. Binding of a candidate splice regulator to a calcitonin-specific splice enhancer regulates calcitonin/CGRP pre-mRNA splicing.

    Science.gov (United States)

    Coleman, Timothy P; Tran, Quincy; Roesser, James R

    2003-01-27

    The calcitonin/calcitonin gene-related peptide (CGRP) pre-mRNA is alternatively processed in a tissue-specific manner leading to the production of calcitonin mRNA in thyroid C cells and CGRP mRNA in neurons. A candidate calcitonin/CGRP splice regulator (CSR) isolated from rat brain was shown to inhibit calcitonin-specific splicing in vitro. CSR specifically binds to two regions in the calcitonin-specific exon 4 RNA previously demonstrated to function as a bipartate exonic splice enhancer (ESE). The two regions, A and B element, are necessary for inclusion of exon 4 into calcitonin mRNA. A novel RNA footprinting method based on the UV cross-linking assay was used to define the site of interaction between CSR and B element RNA. Base changes at the CSR binding site prevented CSR binding to B element RNA and CSR was unable to inhibit in vitro splicing of pre-mRNAs containing the mutated CSR binding site. When expressed in cells that normally produce predominantly CGRP mRNA, a calcitonin/CGRP gene containing the mutated CSR binding site expressed predominantly calcitonin mRNA. These observations demonstrate that CSR binding to the calcitonin-specific ESE regulates calcitonin/CGRP pre-mRNA splicing.

  8. A specific Tween-80-Rhodamine S-MWNTs phosphorescent reagent for the detection of trace calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Liu Jiaming, E-mail: zzsyliujiaming@163.com [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Huang Xiaomei; Zhang Lihong; Zheng Zhiyong [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Department of Food and Biological Engineering, Zhangzhou Institute of Technology, Zhangzhou, 363000 (China); Lin Xuan; Zhang Xiaoyang; Jiao Li; Cui Malin [Department of Chemistry and Environmental Science, Zhangzhou Normal College, Zhangzhou, 363000 (China); Jiang Shulian [Fujian Provincial Bureau of Quality and Technical Supervision, Zhangzhou, 363000 (China); Lin Shaoqin [Department of Biochemistry, Fujian Education College, Fuzhou 350001 (China)

    2012-09-26

    Graphical abstract: A new Tween-80-Rhodamine S-water-soluble multi-walled carbon nanotubes (Tween-80-Rhod.S-MWNTs-EDC-NHS, TRMEN) phosphorescent labelling reagent was developed. High sensitive solid substrate room temperature phosphorescence immunoassay (SSRTPIA) for the determination of calcitonin (CT) in human serum and the prediction of human diseases based on the TRMEN could be used to label anti-calcitonin antibody (Ab{sub CT}) to form the TRMEN-Ab{sub CT} labelling product, which could take high specific immunoreaction with CT causing that the {Delta}I{sub p} of the system was linear to the content of CT. Moreover, the reaction mechanisms of both labelling Ab{sub CT} by TRMEN and SSRTPIA for the determination of trace CT were discussed. This research not only provides a new hormones analysis method, but also expands the application field of MWNTs and promotes the development of SSRTP and IA. --Highlights: Black-Right-Pointing-Pointer A Tween-80-Rhodamine S-multi-walled carbon nanotubes labelling reagent was developed. Black-Right-Pointing-Pointer The phosphorescence immunoassay was established for the determination of calcitonin. Black-Right-Pointing-Pointer This method has been applied to determine CT and the prediction of diseases. Black-Right-Pointing-Pointer The structure of MWNTs was characterized with SEM and IR. Black-Right-Pointing-Pointer The mechanisms for both determining trace CT and labelling Ab{sub CT} were discussed. - Abstract: The present study proposed a simple sensitive and specific immunoassay for the quantification of calcitonin (CT) in human serum with water-soluble multi-walled carbon nanotubes (MWNTs). The -COOH group of MWNTs could react with the -NH- group of rhodamine S (Rhod.S) molecules to form Rhod.S-MWNTs, which could emit room temperature phosphorescence (RTP) on acetate cellulose membrane (ACM) and react with Tween-80 to form micellar compound. Tween-80-Rhod.S-MWNTs (TRM), as a phosphorescent labelling reagent, could

  9. Basal serum cortisol level and its circadian variability in PCOS patients%多囊卵巢综合征基础血清皮质醇水平及其昼夜规律变化

    Institute of Scientific and Technical Information of China (English)

    古芳; 徐艳文; 苗本郁; 朱莉; 王彬; 周灿权

    2012-01-01

    Objective To investigate the basal cortisol level and its circadian rhythm in a cohort of Chinese women with polycystic ovary syndrome (PCOS). Methods A cohort of 63 PCOS women (21 obese and 42 non-obese) and 38 non-obese healthy controls were included in this study. Serum cortisol levels at 8AM and 4PM as well as the rate of loss of cortisol circadian rhythm were compared among the obese PCOS group, non-obese PCOS group and healthy controls. Possible factors associated with the basal cortisol level were analyzed. Results Basal cortisol level in the obese PCOS group, non-obese PCOS group and healthy controls were (325.7 ± 125. 7) nmol/L, (407. 6 ± 165. 6) nmol/L and (397.4 ±129.9) nmol/L, respectively. Obese PCOS group had a lower basal cortisol level than the healthy controls ( P < 0. 05). The ratio of 4PM: 8AM cortisol was higher in the obese(0. 78 ±0. 54) and non-obese PCOS group (0. 61 ±0. 34)than the healthy controls(0. 46 ±0. 20) (P<0. 05). Circadian rhythm loss occurred more frequently in obese PCOS patients (47.6%) than the healthy controls ( 10. 5% ) ( P < 0. 05 ) . Basal cortisol levels were inversely associated with BMI ( P < 0. 05 ). Conclusion Obese PCOS patients have an activated HPA axis,with decreased basal cortisol levels and higher rates of circadian rhythm loss. BMI might play an important role in cortisol metabolism as well as the HPA activation.%目的 探讨多囊卵巢综合征(PCOS)患者基础血清皮质醇水平及其昼夜规律的变化.方法 对2008年7月至2010年5月中山大学附属第一医院生殖医学中心63例PCOS患者(21例肥胖和42例非肥胖)及38名月经正常的健康妇女进行空腹8时(基础)及16时血清皮质醇浓度测定,并比较其昼夜规律消失的比例,同时分析影响基础皮质醇水平的可能相关因素.结果 肥胖PCOS组、非肥胖PCOS组及健康对照组的基础皮质醇水平分别为( 325.7±125.7)nmoL/L,(407.6±165.6) nmol/L和(397.4±129.9) nmol/L.其中肥胖PCOS组

  10. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias.

    Directory of Open Access Journals (Sweden)

    Kim Vietz Andreassen

    Full Text Available Salmon calcitonin (sCT and human calcitonin (hCT are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(aR with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a receptor. CT(aR downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours and prolonged (up to 72 hours stimulation. CT(aR kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(aR downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  11. Prolonged calcitonin receptor signaling by salmon, but not human calcitonin, reveals ligand bias.

    Science.gov (United States)

    Andreassen, Kim Vietz; Hjuler, Sara Toftegaard; Furness, Sebastian G; Sexton, Patrick M; Christopoulos, Arthur; Nosjean, Olivier; Karsdal, Morten Asser; Henriksen, Kim

    2014-01-01

    Salmon calcitonin (sCT) and human calcitonin (hCT) are pharmacologically distinct. However, the reason for the differences is unclear. Here we analyze the differences between sCT and hCT on the human calcitonin receptor (CT(a)R) with respect to activation of cAMP signaling, β-arrestin recruitment, ligand binding kinetics and internalization. The study was conducted using mammalian cell lines heterologously expressing the human CT(a) receptor. CT(a)R downstream signaling was investigated with dose response profiles for cAMP production and β-arrestin recruitment for sCT and hCT during short term (<2 hours) and prolonged (up to 72 hours) stimulation. CT(a)R kinetics and internalization was investigated with radio-labeled sCT and hCT ligands on cultured cells and isolated membrane preparations from the same cell line. We found that sCT and hCT are equipotent during short-term stimulations with differences manifesting themselves only during long-term stimulation with sCT inducing a prolonged activation up to 72 hours, while hCT loses activity markedly earlier. The prolonged sCT stimulation of both cAMP accumulation and β-arrestin recruitment was attenuated, but not abrogated by acid wash, suggesting a role for sCT activated internalized receptors. We have demonstrated a novel phenomenon, namely that two distinct CT(a)R downstream signaling activation patterns are activated by two related ligands, thereby highlighting qualitatively different signaling responses in vitro that could have implications for sCT use in vivo.

  12. Imprinted ZnO nanostructure-based electrochemical sensing of calcitonin: a clinical marker for medullary thyroid carcinoma.

    Science.gov (United States)

    Patra, Santanu; Roy, Ekta; Madhuri, Rashmi; Sharma, Prashant K

    2015-01-01

    The present work describes an exciting method for the selective and sensitive determination of calcitonin in human blood serum samples. Adopting the surface molecular imprinting technique, a calcitonin-imprinted polymer was prepared on the surface of the zinc oxide nanostructure. Firstly, a biocompatible tyrosine derivative as a monomer was grafted onto the surface of zinc oxide nanostructure followed by their polymerization on vinyl functionalized electrode surface by activator regenerated by electron transfer-atom transfer radical polymerization (ARGET-ATRP) technique. Such sensor can predict the small change in the concentration of calcitonin in the human body and it may also consider to be as cost-effective, renewable, disposable, and reliable for clinical studies having no such cross-reactivity and matrix effect from real samples. The morphologies and properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry and chronocoulometry. The linear working range was found to be 9.99 ng L(-1) to 7.919 mg L(-1) and the detection limit as low as 3.09±0.01 ng L(-1) (standard deviation for three replicate measurements) (S/N=3).

  13. Salmon calcitonin: conformational changes and stabilizer effects

    Directory of Open Access Journals (Sweden)

    Shan-Yang Lin

    2015-11-01

    Full Text Available The therapeutic activity of peptides or protein drugs is highly dependent on their conformational structure. The protein structure is flexible and responds to external conditions, which may compromise the protein's native conformation and influence its physical and chemical stability. The physical and chemical stability of peptides or protein drugs are important characteristics of biopharmaceutical products. Calcitonin (CT is a polypeptide hormone that participates in diverse physiological functions in humans; therefore, it is a potentially useful protein for investigations of different aspects of pharmacology and drug delivery systems. Of the different types of CT available for clinical use, salmon CT (sCT is one of the most potent. In this review article, the commercially available sCT was selected as a suitable peptide candidate for the discussion of its stability and conformational changes in the aqueous and solid states using Fourier transform infrared (FTIR spectroscopic analysis under different external conditions, including pH, temperature, drying method, and added excipients. Particularly, excipients that have been optimized as stabilizers of sCT in aqueous solution and as lyophilized and spray-dried drug formulations are also discussed.

  14. Calcitonin gene related peptide and its functions

    Directory of Open Access Journals (Sweden)

    Karimian M

    1998-07-01

    Full Text Available Calcitonin Gene Related Peptide (CGRP was first reported in 1982. This peptide contains 37 amino acids which could be found in Alpha and Beta forms. CGRP shows diversity both in its receptors and biological effects and up to now four different types of receptors have been reported. It can act like a neurotransmitter, local hormone and neuromodulator. They have a variety of effects on different organs such as a potent effect on vasodilation and smooth muscle relaxation. Ability of CGRP for induction of protein extravasation from blood vessels was uncertain. In this study intra-articular infusion of 10^-6 M CGRP to the rat knee joint induced significant protein extravasation into the rat knee joint space. The amount of protein was detected by modified Iawata method which could detect amount of protein between 5-500 mg/L. Higher and lower concentrations failed to induce protein extravasation. Failure in higher concentration was likely due to significant fall in blood pressure. In the presence of an arterial hypotension induced by an ? adenoreceptor antagonist, 10^-6 M of CGRP failed to produce protein extravasation. This effect of CGRP was a specific active effect and not a passive effect due to its potent vasodilation effect, as similar vasodilatory response induced by a ?-adrenoreceptor agonist failed to induce protein extravasation. There is more than 50% of sensory neurons which contain CGRP and they are spread in all over the body and joints, therefore CGRP induced protein extravasation can potentiate inflammation in different organs.

  15. Down-regulation of rat kidney calcitonin receptors by salmon calcitonin infusion evidence by autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Bouizar, Z.; Rostene, W.H.; Milhaud, G.

    1987-08-01

    In treating age-related osteoporosis and Paget disease of bone, it is of major importance to avoid an escape phenomenon that would reduce effectiveness of the treatment. The factors involved in the loss of therapeutic efficacy with administration of large pharmacological doses of the hormone require special consideration. Down-regulation of the hormone receptors could account for the escape phenomenon. Specific binding sites for salmon calcitonin (sCT) were characterized and localized by autoradiography on rat kidney sections incubated with /sup 125/I-labeled sCT. Autoradiograms demonstrated a heterogeneous distribution of /sup 125/I-labeled sCT binding sites in the kidney, with high densities in both the superficial layer of the cortex and the outer medulla. Infusion of different doses of unlabeled sCT by means of Alzet minipumps for 7 days produced rapid changes in plasma calcium, phosphate, and magnesium levels, which were no longer observed after 2 or 6 days of treatment. Besides, infusion of high doses of sCT induced down-regulation of renal sCT binding sites located mainly in the medulla, where calcitonin (CT) has been shown to exert it physiological effects on water and ion reabsorption. These data suggest that the resistance to high doses of sCT often observed during long-term treatment of patients may be the consequence of not only bone-cell desensitization but also down-regulation of CT-sensitive kidney receptor sites.

  16. Scientific considerations for generic synthetic salmon calcitonin nasal spray products.

    Science.gov (United States)

    Lee, Sau L; Yu, Lawrence X; Cai, Bing; Johnsons, Gibbes R; Rosenberg, Amy S; Cherney, Barry W; Guo, Wei; Raw, Andre S

    2011-03-01

    Under the Abbreviated New Drug Application pathway, a proposed generic salmon calcitonin nasal spray is required to demonstrate pharmaceutical equivalence and bioequivalence to the brand-name counterpart or the reference listed drug. This review discusses two important aspects of pharmaceutical equivalence for this synthetic peptide nasal spray product. The first aspect is drug substance sameness, in which a proposed generic salmon calcitonin product is required to demonstrate that it contains the same active ingredient as that in the brand-name counterpart. The second aspect is comparability in product- and process-related factors that may influence immunogenicity (i.e., peptide-related impurities, aggregates, formulation, and leachates from the container/closure system). The comparability of these factors helps to ensure the product safety, particularly with respect to immunogenicity. This review also highlights the key features of in vitro and/or in vivo studies for establishing bioequivalence for a solution nasal spray containing a systemically acting salmon calcitonin.

  17. Salmon calcitonin in the therapy of corticoid-induced osteoporosis.

    Science.gov (United States)

    Ringe, J D; Welzel, D

    1987-01-01

    There is uncertainty about the best treatment for steroid-induced osteoporosis. Thirty-six patients with steroid-dependent, chronic obstructive lung disease and associated steroid osteoporosis have been studied, of whom 18 were treated with salmon calcitonin and the other 18 served as controls. Treatment lasted for 6 months and consisted of 100 I.U.s.c. every other day. In the controls there were significant decrements of 1.4% and 3.5%, respectively, in cortical and cortical and trabecular bone mineral content, whereas in subjects on calcitonin there were increments of 2.6% and 2.7%, respectively. Additional evidence of positive effect of calcitonin was derived from the reduced incidence of new fractures occurring during the observation period. A significant reduction in back pain was a further consequence of the hormone therapy.

  18. [Calcitonin as an alternative treatment for root resorption].

    Science.gov (United States)

    Pierce, A; Berg, J O; Lindskog, S

    1989-01-01

    Inflammatory root resorption is a common finding following trauma and will cause eventual destruction of the tooth root if left untreated. This study examined the effects of intrapulpal application of calcitonin, a hormone known to inhibit osteoclastic bone resorption, on experimental inflammatory root resorption induced in monkeys. Results were histologically evaluated using a morphometric technique and revealed that calcitonin was an effective medicament for the treatment of inflammatory root resorption. It was concluded that this hormone could be a useful therapeutic adjunct in difficult cases of external root resorption.

  19. Calcitonin Gene-Related Peptide (CGRP in Cerebrovascular Disease

    Directory of Open Access Journals (Sweden)

    Lars Edvinsson

    2002-01-01

    Full Text Available Cerebral blood vessels are innervated by sensory nerves that store several neurotransmitters among which calcitonin gene-related peptide (CGRP is the most abundant. In primary headaches, there is a clear association between the head pain and the release of CGRP. In cluster headache there is an additional release of vasoactive intestinal peptide (VIP.

  20. Calcitonin gene-related peptide and adrenomedullin release in humans

    DEFF Research Database (Denmark)

    Hasbak, Philip; Lundby, Carsten; Olsen, Niels Vidiendal;

    2002-01-01

    ). Plasma values of CGRP, AM, calcitonin, noradrenaline, adrenaline, lactate and heart rate were measured at rest and during maximal exercise (W(max)). On each study day, the dopamine D(2)-receptor antagonist, domperidone (30 mg; n=6), or no medication (n=6) was given 1 h before exercise. W(max) at SL, HA1...

  1. 21 CFR 862.1140 - Calcitonin test system.

    Science.gov (United States)

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Calcitonin test system. 862.1140 Section 862.1140 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) MEDICAL DEVICES CLINICAL CHEMISTRY AND CLINICAL TOXICOLOGY DEVICES Clinical Chemistry Test Systems §...

  2. Basal Reinforced Piled Embankments

    NARCIS (Netherlands)

    Van Eekelen, S.J.M.

    2015-01-01

    A basal reinforced piled embankment consists of a reinforced embankment on a pile foundation. The reinforcement consists of one or more horizontal layers of geosynthetic reinforcement (GR) installed at the base of the embankment. The design of the GR is the subject of this thesis. A basal reinforce

  3. Specific binding of /sup 125/I-salmon calcitonin to rat brain. Regional variation and calcitonin specificity

    Energy Technology Data Exchange (ETDEWEB)

    Nakamuta, H.; Furukawa, S.; Koida, M. (Nagasaki Univ. (Japan). Faculty of Pharmaceutical Sciences); Yajima, H.; Orlowski, R.C.

    1981-02-01

    Rat brain particulate fraction was found to contain binding sites for /sup 125/I-Salmon Calcitonin-I (/sup 125/I-SCT). Maximum binding occurred in the physiological pH range of 7.25 - 7.5. The binding reaction proceeded in a temperature-dependent manner. Binding sites were broadly distributed among the various rat brain regions and considerable regional differences existed in the affinity and density as detected by Scatchard analysis. The highest affinity was recorded in the case of the hypothalamus and the lowest in the case of the cerebellum. The KD (nM) and Bmax (pmole/mg protein) estimated for the binding to four regions were as follows: hypothalamus: 1.4 and 0.19, midbrain, hippocampus plus striatum: 1.5 and 0.08, pon plus medulla oblongata: 3.0 and 0.15 and cerebellum: 8.3 and 0.20. Using a particulate fraction of rat brain void of cerebellum and cortices, a binding assay for calcitonins was developed. Binding of /sup 125/I-SCT was inhibited by unlabeled salmon, (Asu sup(1,7))-eel and porcine calcitonins in a dose-dependent manner and the IC50s were 2.0, 8.0 and 30 nM, respectively. The IC50s were comparable to those estimated using a kidney particulate fraction. Human calcitonin, ..beta..-endorphin and substance P were weak inhibitors of the binding. Other peptides, drugs and putative neurotransmitters tested (totally 23 substances) failed to inhibit the binding at concentrations of 1.0 ..mu..M. The physiological significance of brain binding sites for calcitonin, with the possibility that the brain may possess endogenous ligands for these sites are discussed.

  4. Application of the yeast-surface-display system for orally administered salmon calcitonin and safety assessment.

    Science.gov (United States)

    Sun, Ping-Nan; Zhang, Xue-Cheng; Chen, Yun-Song; Zang, Xiao-Nan

    2010-01-01

    High manufacturing costs and oral delivery are the constraints in clinical application of calcitonin. We selected surface-displayed Saccharomyces cerevisiae as a low-cost and safe carrier for oral delivery of salmon calcitonin (sCT). The sCT DNA fragment, optimized according to the codon preference of S. cerevisiae, was synthesized and cloned into the plasmid M-pYD1 to yield recombinant yAGA2-sCT, which was induced to express sCT by galactose for 0, 12, and 24 h. sCT expression was detected on the cell surface by indirect immunofluorescence and peaked at 12 h. About 65% recombinants expressed sCT on flow cytometry. The in vivo and in vitro activity of recombinant sCT was determined by detecting bioactivity of antiosteoclastic absorption on bone wafers and orally administering yAGA2-sCT to Wistar rats, respectively. For safety assessment of yAGA2-sCT, we observed abnormalities, morbidity, and mortality and determined body weight, serum chemistry parameters, hematological parameters, and organ weight. In vitro bioactivity of the recombinant sCT was similar to that of commercial sCT, Miacalcic; oral administration of 5 g/kg yAGA2-sCT induced a long-term hypocalcemic effect in Wistar rats and no adverse effects. This study demonstrates that yAGA2-sCT anchoring sCT protein on a S. cerevisiae surface has potential for low-cost and safe oral delivery of sCT.

  5. Preliminary study on androgen dependence of calcitonin gene-related peptide in rat penis

    Institute of Scientific and Technical Information of China (English)

    Zhou-Jun Shen; Shan-Wen Chen; Ying-Li Lu; Liao-Yuan Li; Xie-Lai Zhou; Ming-Guang Zhang; Zhao-Dian Chen

    2005-01-01

    Aim: To study the androgen dependence of the neurotransmitter, calcitonin gene-related peptide (CGRP) in rat penis.Methods: Forty-four Sprague-Dawley rats were randomly divided into Group A (intact controls), Group B (castrated)group were anaesthetized. Blood samples were taken for the measurement of serum testosterone and dihydrotestosterone (DHT) by means of radioimmunoassay. Penile samples were harvested for the investigation of calcitonin gene related peptide (CGRP)-immunoreactive nerve fibers with immunohistochemistry. The computer-assisted imaging analysis system was applied to calculate the area proportion of the CGRP-positive nerve fibers (CGRP-PNF) in each group.Results: 1) Both 4 and 10 weeks later, testosterone and DHT levels in Group B decreased significantly compared with those in Group A, (P<0.05, P<0.01, respectively); DHT level in Group C was also significantly decreased in comparison with that in Group A for both 4- and 10- week animals (P < 0.05); 2) There was no significant differences in area proportion of CGRP-PNF among Groups A, B and C 4 weeks after treatments (P > 0.05); However, 10weeks later, the proportion of CGRP-PNF in Groups B and C was significantly less than that in Group A (P < 0.01);3) The proportion of CGRP-PNF of 4-week animals in Groups B and C was significantly higher than that of 10-week animals (P<0.05). Conclusion: The expression of neurotransmitter, CGRP may depend on androgens, including testosterone and DHT in rat penis.

  6. Investigation of the direct effects of salmon calcitonin on human osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Pedersen Christian

    2010-04-01

    Full Text Available Abstract Background Calcitonin has been demonstrated to have chondroprotective effects under pre-clinical settings. It is debated whether this effect is mediated through subchondral-bone, directly on cartilage or both in combination. We investigated possible direct effects of salmon calcitonin on proteoglycans and collagen-type-II synthesis in osteoarthritic (OA cartilage. Methods Human OA cartilage explants were cultured with salmon calcitonin [100 pM-100 nM]. Direct effects of calcitonin on articular cartilage were evaluated by 1 measurement of proteoglycan synthesis by incorporation of radioactive labeled 35SO4 [5 μCi] 2 quantification of collagen-type-II formation by pro-peptides of collagen type II (PIINP ELISA, 3 QPCR expression of the calcitonin receptor in OA chondrocytes using four individual primer pairs, 4 activation of the cAMP signaling pathway by EIA and, 5 investigations of metabolic activity by AlamarBlue. Results QPCR analysis and subsequent sequencing confirmed expression of the calcitonin receptor in human chondrocytes. All doses of salmon calcitonin significantly elevated cAMP levels (P 35SO4 incorporation, with a 96% maximal induction at 10 nM (P Conclusion Calcitonin treatment increased proteoglycan and collagen synthesis in human OA cartilage. In addition to its well-established effect on subchondral bone, calcitonin may prove beneficial to the management of joint diseases through direct effects on chondrocytes.

  7. Identification of the calcitonin receptor in osteoarthritic chondrocytes

    Directory of Open Access Journals (Sweden)

    Christensen Tjorbjoern

    2011-10-01

    Full Text Available Abstract Background Preclinical and clinical studies have shown that salmon calcitonin has cartilage protective effects in joint degenerative diseases, such as osteoarthritis (OA. However, the presence of the calcitonin receptor (CTR in articular cartilage chondrocytes is yet to be identified. In this study, we sought to further investigate the expression of the CTR in naïve human OA articular chondrocytes to gain further confirmation of the existents of the CTR in articular cartilage. Methods Total RNA was purified from primary chondrocytes from articular cartilage biopsies from four OA patients undergoing total knee replacement. High quality cDNA was produced using a dedicated reverse transcription polymerase chain reaction (RT-PCR protocol. From this a nested PCR assay amplifying the full coding region of the CTR mRNA was completed. Western blotting and immunohistochemistry were used to characterize CTR protein on protein level in chondrocytes. Results The full coding transcript of the CTR isoform 2 was identified in all four individuals. DNA sequencing revealed a number of allelic variants of the gene including two potentially novel polymorphisms: a frame shift mutation, +473del, producing a shorter form of the receptor protein, and a single nucleotide polymorphism in the 3' non coding region of the transcript, +1443 C>T. A 53 kDa protein band, consistent with non-glycosylated CTR isoform 2, was detected in chondrocytes with a similar size to that expressed in osteoclasts. Moreover the CTR was identified in the plasma membrane and the chondrocyte lacuna of both primary chondrocytes and OA cartilage section. Conclusions Human OA articular cartilage chondrocytes do indeed express the CTR, which makes the articular a pharmacological target of salmon calcitonin. In addition, the results support previous findings suggesting that calcitonin has a direct anabolic effect on articular cartilage.

  8. Calcitonin gene-related peptide and migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Ashina, Messoud

    2014-01-01

    BACKGROUND: Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathophysiology. Most studies have focused on CGRP in relation to migraine without aura (MO). About one-third of migraine patients have attacks with aura (MA), and this is a systematic review of the current literature...... of CGRP in MA is less studied than in MO. Further studies of the importance of CGRP for auras and migraine are needed....

  9. Imprinted ZnO nanostructure-based electrochemical sensing of calcitonin: A clinical marker for medullary thyroid carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Patra, Santanu; Roy, Ekta [Department of Applied Chemistry, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India); Madhuri, Rashmi, E-mail: rshmmadhuri@gmail.com [Department of Applied Chemistry, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India); Sharma, Prashant K. [Functional Nanomaterials Research Laboratory, Department of Applied Physics, Indian School of Mines, Dhanbad, Jharkhand 826 004 (India)

    2015-01-01

    Highlights: • Molecular imprinting-based sensor for medullary thyroid carcinoma marker was developed. • ZnO nanostructure was used as a platform for synthesis of imprinted polymer. • Imprinted polymer was prepared by ARGET–ATRP method. • A novel and biocompatible tyrosine amino acid derivative was used as monomer. • Linear working range is found from 9.99 ng L{sup −1} to 7.919 mg L{sup −1} with LOD 3.09 ng L{sup −1}. - Abstract: The present work describes an exciting method for the selective and sensitive determination of calcitonin in human blood serum samples. Adopting the surface molecular imprinting technique, a calcitonin-imprinted polymer was prepared on the surface of the zinc oxide nanostructure. Firstly, a biocompatible tyrosine derivative as a monomer was grafted onto the surface of zinc oxide nanostructure followed by their polymerization on vinyl functionalized electrode surface by activator regenerated by electron transfer–atom transfer radical polymerization (ARGET–ATRP) technique. Such sensor can predict the small change in the concentration of calcitonin in the human body and it may also consider to be as cost-effective, renewable, disposable, and reliable for clinical studies having no such cross-reactivity and matrix effect from real samples. The morphologies and properties of the proposed sensor were characterized by scanning electron microscopy, cyclic voltammetry, difference pulse voltammetry and chronocoulometry. The linear working range was found to be 9.99 ng L{sup −1} to 7.919 mg L{sup −1} and the detection limit as low as 3.09 ± 0.01 ng L{sup −1} (standard deviation for three replicate measurements) (S/N = 3)

  10. Conformational flexibility in calcitonin: The dynamic properties of human and salmon calcitonin in solution

    Energy Technology Data Exchange (ETDEWEB)

    Amodeo, Pietro; Motta, Andrea; Strazzullo, Giuseppe [Istituto per la Chimica di Molecole di Interesse Biologico, Istituto Nazionale di Chimica dei sistemi Biologici del CNR (Italy); Castiglione Morelli, Maria A. [Universita della Basilicata, Dipartimento di Chimica (Italy)

    1999-02-15

    We have studied the dynamic properties of human (h) and salmon (s) calcitonin (CT) in solution. For both hormones, distance geometry in torsion-angle space has been used to generate three-dimensional structures consistent with NMR data obtained in sodium dodecyl sulfate micelles. For sCT and hCT we used, respectively, 356 and 275 interproton distances together with hydrogen-bonds as restraints. To better characterize their flexibility and dynamic properties two fully unrestrained 1100-ps molecular dynamics (MD) simulations in methanol were performed on the lowest-energy structures of both hormones. Statistical analyses of average geometric parameters and of their fluctuations performed in the last 1000 ps of the MD run show typical helical values for residues 9-19 of sCT during the whole trajectory. For hCT a shorter helix was observed involving residues 13-21, with a constant helical region in the range 13-19. Angular order parameters S({phi}) and S({psi}) indicate that hCT exhibits a higher flexibility, distributed along the whole chain, including the helix, while the only flexible amino acid residues in sCT connect three well-defined domains. Finally, our study shows that simulated annealing in torsion-angle space can efficiently be extended to NMR-based three-dimensional structure calculations of helical polypeptides. Furthermore, provided that a sufficient number of NMR restraints describes the system, the method allows the detection of equilibria in solution. This identification occurs through the generation of 'spurious' high-energy structures, which, for right-handed {alpha}-helices, are likely to be represented by left-handed {alpha}-helices.

  11. Effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone mineral density and bone metabolism in patients with senile osteoporotic compression fractures

    Institute of Scientific and Technical Information of China (English)

    Li Li; Yu Si

    2016-01-01

    Objective:To analyze the effect of Qianggu Capsule combined with salmon calcitonin injection treatment on bone mineral density and bone metabolism in patients with senile osteoporotic compression fractures.Methods: A total of 92 cases of patients with senile osteoporotic compression fractures were divided into observation group and control group (n=46) according to random number table, control group received Qianggu Capsule treatment alone, observation group received Qianggu Capsule combined with salmon calcitonin injection treatment, and the differences in bone mineral density, bone metabolism indexes and CT-related parameters were compared between two groups.Results: BMD values of observation group after 3 courses and 6 courses of treatment were higher than those of control group; serum BGP and PTH values of observation group after treatment were higher than those of control group, CICP and CTX-Ⅰ values were lower than those of control group, and urine D-Pyr value was lower than that of control group; CV and CV/MV values of observation group after treatment were higher than those of control group, and MV value was lower than that of control group.Conclusion: Qianggu Capsule combined with salmon calcitonin injection can inhibit the disease progression in patients with senile osteoporotic compression fractures, optimize bone metabolism and promote osteogenesis, and it has positive clinical significance.

  12. Activities of calcitonin gene-related peptide (CGRP) and related peptides at the CGRP receptor

    Energy Technology Data Exchange (ETDEWEB)

    Maton, P.N.; Pradhan, T.; Zhou, Z.C.; Gardner, J.D.; Jensen, R.T. (National Institute of Diabetes, Digestive and Kidney Diseases, Bethesda, MD (USA))

    1990-05-01

    In guinea pig pancreatic acini rat calcitonin gene-related peptide (CGRP) increased amylase release 2-fold, salmon calcitonin had an efficacy of only 44% of that of CGRP and (Tyr0)CGRP(28-37) and human calcitonin had no actions. (Tyr0)CGRP(28-37), but not human calcitonin, antagonized the actions of CGRP in pancreatic acini with an IC50 of 3 microM. (Tyr0)CGRP(28-37) produced a parallel rightward shift in the dose-response curve for CGRP-stimulated amylase secretion. The inhibition was specific for CGRP and was reversible. Studies with 125I-CGRP demonstrated that CGRP, salmon calcitonin and (Tyr0)CGRP, but not human calcitonin, interacted with CGRP receptors on pancreatic acini. These results indicate that various CGRP-related peptides demonstrate different relationships between their abilities to occupy the CGRP receptor and to affect biologic activity, with CGRP itself being a full agonist, salmon calcitonin a partial agonist, (Tyr0)CGRP(28-37) a competitive antagonist, and human calcitonin having no actions.

  13. Novel Secondary Structure of Calcitonin in Solid State as Revealed by Circular Dichroism Spectroscopy

    Institute of Scientific and Technical Information of China (English)

    DU,Hai-Ning(杜海宁); DING,Jin-Guo(丁金国); CUI,Da-Fu(崔大敷); HU,Hong-Yu(胡红雨)

    2002-01-01

    The solid-state circular dichroic study reveals that salmon calcitonin presents a typical α-helical structure while human calcitonin appears to form a β-sheet in solid state, although both of them adopt random coil structures in aqueous solution.

  14. Stability aspects of salmon calcitonin entrapped in poly(ether-ester) sustained release systems

    NARCIS (Netherlands)

    Dijkhuizen-Radersma, van R.; Nicolas, H.M.; Weert, van de M.; Blom, M.; Groot, de K.; Bezemer, J.M.

    2002-01-01

    Poly(ether-ester)s composed of hydrophilic poly(ethylene glycol)-terephthalate (PEGT) blocks and hydrophobic poly(butylene terephthalate) (PBT) blocks were studied as matrix for the controlled release of calcitonin. Salmon calcitonin loaded PEGT/PBT films were prepared from water-in-oil emulsions. T

  15. Salmon calcitonin reduces oxaliplatin-induced cold and mechanical allodynia in rats.

    Science.gov (United States)

    Aoki, Manahito; Mori, Asami; Nakahara, Tsutomu; Sakamoto, Kenji; Ishii, Kunio

    2013-01-01

    Oxaliplatin is commonly used anti-cancer drugs, but it frequently causes peripheral neuropathic pain. Recently, we reported that elcatonin, a synthetic analog of eel calcitonin, attenuated the oxaliplatin- and paclitaxel-induced cold and mechanical allodynia in rats. In the present study, we determined whether salmon calcitonin also had anti-allodynic effects on oxaliplatin-induced neuropathy in rats. The rats were treated with a single dose of oxaliplatin (6 mg/kg, intraperitoneally (i.p.)). Oxaliplatin resulted in cold and mechanical allodynia. We assessed the anti-allodynic effects of subcutaneously administered salmon calcitonin (20 U/kg/d) by cold stimulation (8°C) directly to the hind paw of the rats and by using the von Frey test. Salmon calcitonin almost completely reversed the effects of both cold and mechanical allodynia. These results suggest that salmon calcitonin is also useful for treatment of oxaliplatin-induced neuropathy clinically.

  16. Anti-hyperalgesic effects of calcitonin on neuropathic pain interacting with its peripheral receptors

    Directory of Open Access Journals (Sweden)

    Ito Akitoshi

    2012-06-01

    Full Text Available Abstract Background The polypeptide hormone calcitonin is clinically well known for its ability to relieve neuropathic pain such as spinal canal stenosis, diabetic neuropathy and complex regional pain syndrome. Mechanisms for its analgesic effect, however, remain unclear. Here we investigated the mechanism of anti-hyperalgesic action of calcitonin in a neuropathic pain model in rats. Results Subcutaneous injection of elcatonin, a synthetic derivative of eel calcitonin, relieved hyperalgesia induced by chronic constriction injury (CCI. Real-time reverse transcriptase-polymerase chain reaction analysis revealed that the CCI provoked the upregulation of tetrodotoxin (TTX-sensitive Nav.1.3 mRNA and downregulation of TTX-resistant Nav1.8 and Nav1.9 mRNA on the ipsilateral dorsal root ganglion (DRG, which would consequently increase the excitability of peripheral nerves. These changes were reversed by elcatonin. In addition, the gene expression of the calcitonin receptor and binding site of 125I-calcitonin was increased at the constricted peripheral nerve tissue but not at the DRG. The anti-hyperalgesic effect and normalization of sodium channel mRNA by elcatonin was parallel to the change of the calcitonin receptor expression. Elcatonin, however, did not affect the sensitivity of nociception or gene expression of sodium channel, while it suppressed calcitonin receptor mRNA under normal conditions. Conclusions These results suggest that the anti-hyperalgesic action of calcitonin on CCI rats could be attributable to the normalization of the sodium channel expression, which might be exerted by an unknown signal produced at the peripheral nerve tissue but not by DRG neurons through the activation of the calcitonin receptor. Calcitonin signals were silent in the normal condition and nerve injury may be one of triggers for conversion of a silent to an active signal.

  17. PK/PD modelling of comb-shaped PEGylated salmon calcitonin conjugates of differing molecular weights.

    Science.gov (United States)

    Ryan, Sinéad M; Frías, Jesús M; Wang, Xuexuan; Sayers, Claire T; Haddleton, David M; Brayden, David J

    2011-01-20

    Salmon calcitonin (sCT) was conjugated via cysteine-1 to novel comb-shaped end-functionalised (poly(PEG) methyl ether methacrylate) (sCT-P) polymers, to yield conjugates of total molecular weights (MW) inclusive of sCT: 6.5, 9.5, 23 and 40kDa. The conjugates were characterised by HPLC and their in vitro and in vivo bioactivity was measured by cAMP assay on human T47D cells and following intravenous (i.v.) injection to rats, respectively. Stability against endopeptidases, rat serum and liver homogenates was assessed. There were linear and exponential relationships between conjugate MW with potency and efficacy respectively, however the largest MW conjugate still retained 70% of E(max) and an EC(50) of 3.7nM. In vivo, while free sCT and the conjugates reduced serum [calcium] to a maximum of 15-30% over 240 min, the half-life (T(1/2)) was increased and the area under the curve (AUC) was extended in proportion to conjugate MW. Likewise, the polymer conferred protection on sCT against attack by trypsin, chymotrypsin, elastase, rat serum and liver homogenates, with the best protection afforded by sCT-P (40kDa). Mathematical modelling accurately predicted the MW relationships to in vitro efficacy, potency, in vivo PK and enzymatic stability. With a significant increase in T(1/2) for sCT, the 40kDa MW comb-shaped PEG conjugate of sCT may have potential as a long-acting injectable formulation.

  18. [Drug therapy for osteoporosis associated with rheumatoid arthritis (calcitonin)].

    Science.gov (United States)

    Ide, M; Suzuki, Y

    2001-05-01

    Calcitonin (CT) inhibits osteoclastic bone resorption and also exhibits long-lasting analgestic action, probably mediating through intrinsic serotonin and opioid peptides. The injection form of eel and salmon CT is only available in Japan. There are a few RCT data regarding the effect of CT on osteoporosis associated with RA, the previous studies have shown its effectiveness in terms of maintaining or increasing bone mineral density in RA patients with or without corticosteroid therapy. RA patients with high turnover osteoporosis and back pain might be a good indication of CT therapy.

  19. Study of Calcitonin and Calcitonin Gene-related Peptide in Patients with Medullary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    Ming Gao; Yang Yu; Shuling Li; Benyi Xu; Baocun Sun; Jingzu Liu

    2005-01-01

    OBJECTIVE To provide a basis for treatment and prognosis for MTC patients by investigating CT and CGRP.METHODS Fifty-eight cases of MTC were selected and the relationship between the CT levels and metastasis was investigated. An immunohistochemical method was used to detect the expression of CT and CGRP in the 58 samples of MTC tissues. The CT and CGRP of new MTC inpatients were measured before operation and in the first few days after operation using a radioimmunoassy.RESULTS 1 ) The metastatic rate of cervical lymph nodes was a significantly different between the normal serum CT group and the elevated group (P<0.01). 2) The rate of residual tumor was significantly different between the normal serum CT group one month after operation and the elevated group at the same period (P<0.01). 3) In the immunohistochemical study we found the positive rate of CT was about 98%, and the CGRP was 87.8%. 4) Part of the patients had an elevated CGRP level while CT levels were normal. 5) The serum CT levels dropped to a stable range one week after operation.CONCLUSION The CT levels are a useful index to evaluate the probability of cervical lymph node metastasis and the efficacy of surgical treatment.Measurement of the serum CGRP is an aid for the diagnosis of MTC,especially for those patients whose preoperative CT levels are normal.

  20. C reactive protein, calcitonin and D-dimer in patients of community acquired pneumonia

    Institute of Scientific and Technical Information of China (English)

    Xue-Lin Zhang; Zhen Wang; Shu-Hui Lv; Hai-Jun Jing; Jian-Yun Kang; Jian-Qing Zhao

    2016-01-01

    Objective:To investigate the clinical significance of C- reactive protein (CRP), calcitonin (PCT) and D- two (D-D) in community acquired pneumonia.Methods:A total of 102 patients with community-acquired pneumonia (CAP) admitted from March 2015- March 2016 as the research objects. A total of 5 mL peripheral venous blood of CAP patients (within 24 h of admission, before antibiotic therapy) were collected, and centrifuged to obtain serum. Immune turbidimetric method was used in determination of CRP and DD, immune fluorescence method was used for determination of PCT.Results:As grade increasing, the levels of CRP, PCT, D-D were increased gradually, with significant difference among different levels (P<0.05); CRP, PCT and D-D levels of severe group were significantly higher than those of non severe group (P<0.05); death group, CRP, PCT and D-D levels of death group were significantly higher than those of the survival group (P< 0.05).Conclusions:CRP, PCT, D-D levels have certain correlation with degree of severity. They can be used as important indicators to judge the severity of the disease, and predict the prognosis. High levels of CRP, PCT, D-D indicate severity of the disease and poor prognosis.

  1. Preparation and in vitro-in vivo evaluation of salmon calcitonin-loaded polymeric nanoparticles.

    Science.gov (United States)

    Glowka, Eliza; Sapin-Minet, Anne; Leroy, Pierre; Lulek, Janina; Maincent, Philippe

    2010-01-01

    The aim of the study was to develop and characterize polymeric nanoparticles as a sustained release system for salmon calcitonin (sCT). Nanoparticles were prepared by a double emulsion solvent evaporation method using Eudragit RS and two types of a biodegradable poly(lactic-co-glycolic) copolymer (PLGA). It was demonstrated that sCT was incorporated into nanoparticles with encapsulation efficiencies in the range 69-83%. In vitro release studies, unconventionally conducted in 5% acetic acid, showed great differences in sCT release time profiles. Nanoparticles with fast release profile (Eudragit RS, PLGA/Eudragit RS) released 80-100% of the encapsulated drug within a few hours. In contrast, the sCT release from pure PLGA nanoparticles was very slow, incomplete and reached only 20% after 4 weeks. In vivo study, conducted in Wistar rats, proved that elevated serum sCT levels could be sustained for 3 days after subcutaneous administration of PLGA nanoparticles and the achieved bioavailability was increased compared to sCT solution.

  2. An intra-articular salmon calcitonin-based nanocomplex reduces experimental inflammatory arthritis.

    Science.gov (United States)

    Ryan, Sinéad M; McMorrow, Jason; Umerska, Anita; Patel, Hetal B; Kornerup, Kristin N; Tajber, Lidia; Murphy, Evelyn P; Perretti, Mauro; Corrigan, Owen I; Brayden, David J

    2013-04-28

    Prolonged inappropriate inflammatory responses contribute to the pathogenesis of rheumatoid arthritis (RA) and to aspects of osteoarthritis (OA). The orphan nuclear receptor, NR4A2, is a key regulator and potential biomarker for inflammation and represents a potentially valuable therapeutic target. Both salmon calcitonin (sCT) and hyaluronic acid (HA) attenuated activated mRNA expression of NR4A1, NR4A2, NR4A3, and matrix metalloproteinases (MMPs) 1, 3 and 13 in three human cell lines: SW1353 chondrocytes, U937 and THP-1 monocytes. Ad-mixtures of sCT and HA further down-regulated expression of NR4A2 compared to either agent alone at specific concentrations, hence the rationale for their formulation in nanocomplexes (NPs) using chitosan. The sCT released from NP stimulated cAMP production in human T47D breast cancer cells expressing sCT receptors. When NP were injected by the intra-articular (I.A.) route to the mouse knee during on-going inflammatory arthritis of the K/BxN serum transfer model, joint inflammation was reduced together with NR4A2 expression, and local bone architecture was preserved. These data highlight remarkable anti-inflammatory effects of sCT and HA at the level of reducing NR4A2 mRNA expression in vitro. Combining them in NP elicits anti-arthritic effects in vivo following I.A. delivery.

  3. Comparison of Calcitonin Gene Related Peptide Level between Children with Dilated Cardiomyopathy and Control Group

    Directory of Open Access Journals (Sweden)

    Noormohammad Noori

    2015-06-01

    Full Text Available Background: Dilated cardiomyopathy is revealed with left ventricular dilatation and systolic dysfunction. Objectives: This study aimed to compare the children with dilated cardiomyopathy and control group regarding the level of Calcitonin Gene Related Peptide (CGRP and its relationship with echocardiography findings Patients and Methods: This case-control study was conducted on 37 children with dilated cardiomyopathy and free of any clinical symptoms and 37 healthy age- and sex-matched children referring to Ali-e-Asghar and Ali Ebne Abitaleb hospitals in Zahedan, Iran. After taking history, echocardiography was performed for both groups. The data were analyzed using the SPSS statistical software and appropriate statistical tests. Results: The two groups were significantly different regarding most of the echocardiographic parameters (P < 0.05. Also, a significant difference was found between the two groups concerning the mean CGRP levels (P = 0.001. Among echocardiographic parameters, CGRP was directly related to Interventricular Septal dimension in Systole (IVSS (P = 0.022, R = 0.375. However, no significant relationship was observed between CGRP level and Ross classification. Conclusions: The findings of this study showed an increase in CGRP serum levels in the case group. Besides, a direct correlation was observed between CGRP level and IVSS.

  4. [Effectiveness of intranasal salmon calcitonin treatment in postmenopausal osteoporosis].

    Science.gov (United States)

    Kopaliani, M

    2005-04-01

    The aim of this study was to assess clinical efficacy of intranasal salmon calcitonin (Miacalcic, Novartis pharma) treatment in women with established postmenopausal osteoporosis. 30 women of the main group with established postmenopausal osteoporosis(T-score salmon calcitonin: 200 IU daily for 2 months with subsequent pause of 2 months (3 cycles), 12 months in total. Age matched control group was formed by 25 postmenopausal women with similar clinical status. SOS (speed of sound) of cortical bone was measured in the middle of the tibia by ultrasound densitometer--Sound Scan Compact (Myriad-Israel). Patients of both groups received 500 mg Ca and 200 IU vit.D3 (CaD3 Nycomed) two times daily in the same regimen (two months treatment--two months pause). Our results showed that intranasal treatment with 200 IU daily effectively influence the back pain, reduces bone turnover and significantly increases cortical BMD. Significant changes were not observed in patients of the control group, who received only CaD3 Nycomed, that showed that Calcium and vitamin D supplementation is more effective for prevention of bone lose in postmenopausal women, rather for treatment of established osteoporosis.

  5. Localization and characterization of renal calcitonin receptors by in vitro autoradiography

    Energy Technology Data Exchange (ETDEWEB)

    Sexton, P.M.; Adam, W.R.; Moseley, J.M.; Martin, T.J.; Mendelsohn, F.A.

    1987-12-01

    Calcitonin receptors were identified in renal cortex and medulla using the radioligand /sup 125/I-salmon calcitonin. Microscopic localization of these receptors revealed binding over medullary and cortical thick ascending limb of the loop of Henle and in distal convoluted tubule. A number of receptor positive cells in the inner medulla were also identified. Characterization of the binding demonstrated a single class of high-affinity binding sites in both the medulla and the cortex with affinity constants of 0.74 +/- 0.09 x 10(9) M-1 and 0.32 +/- 0.05 x 10(9) M-1, respectively, and receptor concentrations of 205 +/- 45 fmol/mg protein and 453 +/- 54 fmol/mg protein, respectively. Competition for /sup 125/I-salmon calcitonin binding by a wide range of calcitonin analogs revealed a close correspondence between the reported biological potencies and activities in the current system. The localization of binding sites within the nephron corresponds to the reported localization of calcitonin-stimulated adenylate cyclase activity and suggests that the receptor mediated actions of calcitonin in the kidney utilize cyclic AMP as a second messenger. In addition, the microscopic identification of specific calcitonin receptors helps the delineation of direct actions of this hormone from those which are indirect.

  6. Calcitonin-Induced Effects on Amniotic Fluid-Derived Mesenchymal Stem Cells

    Directory of Open Access Journals (Sweden)

    Caterina Morabito

    2015-05-01

    Full Text Available Background/Aims: Mesenchymal stem cells from human amniotic fluid (huAFMSCs can differentiate into multiple lineages and are not tumorigenic after transplantation, making them good candidates for therapeutic purposes. The aim was to determine the effects of calcitonin on these huAFMSCs during osteogenic differentiation, in terms of the physiological role of calcitonin in bone homeostasis. Methods: For huAFMSCs cultured under different conditions, we assayed: expression of the calcitonin receptor, using immunolabelling techniques; proliferation and osteogenesis, using colorimetric and enzymatic assays; intracellular Ca2+ and cAMP levels, using videomicroscopy and spectrophotometry. Results: The calcitonin receptor was expressed in proliferating and osteo-differentiated huAFMSCs. Calcitonin triggered intracellular Ca2+ increases and cAMP production. Its presence in cell medium also induced dose-dependent inhibitory effects on proliferation and increased osteogenic differentiation of huAFMSCs, as also indicated by enhancement of specific markers and alkaline phosphatase activity. Conclusions: These data show that huAFMSCs represent a potential osteogenic model to study in-vitro cell responses to calcitonin (and other members of the calcitonin family. This leads the way to the opening of new lines of research that will add new insight both in cell therapies and in the pharmacological use of these molecules.

  7. Neuropsychiatry of the basal ganglia

    OpenAIRE

    Ring, H.; Serra-Mestres, J

    2002-01-01

    This review aims to relate recent findings describing the role and neural connectivity of the basal ganglia to the clinical neuropsychiatry of basal ganglia movement disorders and to the role of basal ganglia disturbances in "psychiatric"' states. Articles relating to the relevant topics were initially collected through MEDLINE and papers relating to the clinical conditions discussed were also reviewed. The anatomy and connections of the basal ganglia indicate that these structures are import...

  8. Radionuclide conjugates of calcitonin for imaging bone disease and cancer

    Energy Technology Data Exchange (ETDEWEB)

    Greenland, William Edward Peverell

    2002-07-01

    Salmon calcitonin (sCt) is a peptide with a higher affinity for human calcitonin receptors (hCtR) than human calcitonin. It has been used for treating osteoporosis, Paget's disease and bone pain. High levels of hCtRs are expressed on osteoclasts, bone metastases and primary breast and prostate cancers. The peptide was chosen for radiolabelling as a possible imaging agent. Direct labelling with {sup 99m}Tc via simultaneous reduction of the indigenous disulfide bond and {sup 99m}TcO{sub 4}{sup -} (VII) with the water soluble phenyl phosphine (TPPDS) was performed. The radiolabelled peptide was not suitable for use as a radiopharmaceutical due to the heterogeneity of the product as observed by reverse phase HPLC and due to poor binding to the human breast cancer cell line MCF7. The electospray MS suggested a {sup 99}Tc-TPPDS (III) core instead of the expected {sup 99}Tc=O (V) core. Normal sCt has 3 conjugatible primary amines leading to a mixture of 8 possible products. A sCt analogue (sCtA) with a single primary amine was produced and conjugated to the chelator TETA to produce a single conjugated species. The sCtA-TETA was labelled with cold Cu and characterised by electospray MS. The monodentate ligand Hynic was synthesised directly into the peptide using N-{alpha}-Fmoc-N-{epsilon}-(Hynic-Boc)-Lys a novel orthogonally protected amino acid. The peptide was labelled with {sup 99m}Tc with tricine coligands. The radiolabelled peptide produced a single peak as observed by reverse phase HPLC and bound to MCF7 cell in a specific manner. The electospray MS suggested that one of the tricine coligands is lost due to the heating effect and possibly replaced by an adjacent histidine acting as a ternary ligand. The sCtLys{sup 18}-Hynic{sup 99m}Tc(tricine){sub 2} labelled peptide is the lead radiolabelled peptide and could be used for a normal biodistribution animal study, followed by clinical evaluation in humans. (author)

  9. [Effect of calcitonin, somatostatin and cimetidine on stress ulcer in rats].

    Science.gov (United States)

    Jakesz, R; Hofbauer, F; Lehr, L; Schiessel, R

    1978-05-01

    The prophylactic effect of calcitonin, somatostatin and cimetidine on stress ulcer formation in rats was investigated in two stress models: restraint + ketamin (4 h) and hypovolemia (4 h). The basis of the comparative study was a 70% inhibition of acid secretion for 4 h in pyloric ligated animals. This was achieved with 1000 microgram/kg somatostatin s.c., 10 microgram/kg calcitonin s.c., and 2 X 100 mumol/kg cimetidine s.c. In restraint stress and ketamin with calcitonin and cimetidine a significantly lower frequency of gastric lesions was found than with somatostatin. The most potent substance in hypovolemia was calcitonin, with a significant difference in the frequency of mucosal lesions to the groups with cimetidine and somatostatin.

  10. Calcitonin-negative primary neuroendocrine tumor of the thyroid (nonmedullary) in a dog

    Science.gov (United States)

    Arias, E.A. Soler; Castillo, V.A.; Aristarain, M.E. Caneda

    2016-01-01

    The Calcitonin-negative neuroendocrine tumor of the thyroid (CNNET) or “nonmedullary” in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of expression for calcitonin. An Argentine dogo bitch showed a solid, compact thyroid tumor, which was IHC negative for the expression of calcitonin, carcinoembryonic antigen, thyroglobulin and S100 protein, and positive for synaptophysin and cytokeratin AE1-AE3. The Ki-67 proliferation index was low. We cite this case not only because it is the first case report of calcitonin-negative primary neuroendocrine tumor of the thyroid in dogs but also because we want to highlight the diagnostic importance of IHC in this regard. PMID:27928520

  11. Involvement of calcitonin gene-related peptide in migraine

    DEFF Research Database (Denmark)

    Lassen, L H; Jacobsen, V B; Haderslev, P A

    2008-01-01

    mug/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V (mean)) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (halphaCGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of halphaCGRP (2...

  12. Calcitonin gene-related peptide in cervicogenic headache

    DEFF Research Database (Denmark)

    Frese, Amalie; Schilgen, M; Edvinsson, L

    2005-01-01

    Trigeminovascular activation is involved in the pathophysiology of migraine and cluster headache. The marker evaluated best for trigeminovascular activation is calcitonin gene-related peptide (CGRP) in the cranial circulation. It is unknown whether trigeminovascular activation plays any role...... in cervicogenic headache (CEH). The objective of this study was to investigate CGRP plasma levels in CEH patients in relation to headache state. To compare plasma CGRP levels between the peripheral and the cranial circulation. Blood from both external jugular veins and from the antecubital vein was drawn from 11...... patients with CEH. Plasma CGRP levels were measured by radioimmunoassay. No difference was found between CGRP levels assessed on days with and without headache. There was no difference between CGRP levels from the symptomatic and the asymptomatic external jugular vein and the antecubital vein...

  13. 血降钙素原在儿童化脓性脑膜炎与病毒性脑膜炎中的鉴别诊断价值%Differential diagnosis value of serum calcitonin level in children with purulent meningitis and viral meningitis

    Institute of Scientific and Technical Information of China (English)

    任磊; 周启立; 刘霞; 祁宏亮; 刘丽娜

    2016-01-01

    Objective To investigate the value of serum procalcitonin (PCT) level in the differential diagnosis of purulent meningitis and viral meningitis in children.Methods Clinical data of 47 children with acute meningitis,admitted to our hospital from January 2013 to January 2015,were analyzed.Among them,21 were purulent meningitis and 26 were viral meningitis.All children accepted tests as cerebrospinal fluid,serum PCT,C-reactive protein (CRP),and erythrocyte sedimentation (ES) inspection;and comparison of results between the two groups was performed.Results The PCT,CRP and ES levels in the purulent meningitis group were (51.96±30.72) μg/L,(182.33±54.49) mag/L,(50.41± 892) mm/h;and those in the viral meningitis group were (0.81 ±0.96) μg/L,(8.87±10.63) mg/L and (16.72±13.20) mm/h;significant differences were noted between the two groups (P<0.05).There were 3 children with viral meningitis having PCT level higher than 0.5 μg/L,while all patients with purulent meningitis having PCT level higher than 0.5 μg/L,enjoying sensitivity and specificity of 100% and 88.46%.There were 8 children with viral meningitis having ES level higher than 20 mm/h,while 19 patients with purulent meningitis having ES level higher than 20 mm/h,enjoying sensitivity and specificity of 90.48% and 69.23%.Area under receiver operating characteristic curve of PCT was 0.982 (95%CI=0.951-1.011),CRP was 0.981 (95%CI=0.952-1.010),without difference.Conclusion PCT has an important diagnostic value in the differential diagnosis of purulent meningitis and viral meningitis in children,which is better than ESR diagnosis.%目的 探讨血降钙素原(PCT)在鉴别诊断儿童化脓性脑膜炎(细菌性脑膜炎)与病毒性脑膜炎中的价值. 方法 收集承德医学院附属医院小儿内科自2013年1月至2015年1月收治的47例急性脑膜炎患儿的临床资料,其中化脓性脑膜炎21例、病毒性脑膜炎26例.所有患儿入院后均接受脑脊液

  14. Low-Level Laser Therapy and Calcitonin in Bone Repair: Densitometric Analysis

    Directory of Open Access Journals (Sweden)

    Tatiana Pinto Ribeiro

    2012-01-01

    Full Text Available The aim of this work was to evaluate the association of low-level laser therapy (LLLT, 830 nm and calcitonin in bone repair considering that bone healing remains a challenge to health professionals. Calcitonin has antiosteoclastic action and LLLT is a treatment that uses low-level lasers or light-emitting diodes to alter cellular function. Both are used to improve bone healing. Densitometry is a clinical noninvasive valuable tool used to evaluate bone mineral density (BMD. Sixty male rats were submitted to bone defect with a trephine bur, randomly divided into four groups of 15 animals each: control (C; synthetic salmon calcitonin (Ca; LLLT (La; LLLT combined with calcitonin (LaCa. Animals from Ca and LaCa received 2 UI/Kg synthetic salmon calcitonin intramuscularly on alternate days after surgery. Animals from groups La and LaCa were treated with infrared LLLT (830 nm, 10 mW, 20 J/cm2, 6 s, contact mode. Five animals from each group were euthanized 7, 14, and 21 days after surgery and bone defects were analyzed by densitometry. Statistical analysis showed a significant difference in BMD values in LaCa group at 7 and 21 days (=0,005. The results of the densitometric study showed that LLLT (830 nm combined with calcitonin improved bone repair.

  15. Vismodegib in basal cell carcinoma.

    Science.gov (United States)

    Amaria, R N; Bowles, D W; Lewis, K D; Jimeno, A

    2012-07-01

    Vismodegib is a novel, small-molecule inhibitor of smoothened, a key component of the hedgehog signaling pathway. Increased hedgehog pathway signaling is critical in the development of hereditary and spontaneous basal cell carcinomas of the skin, and has been implicated in the development of a number of other tumors. In preclinical models, vismodegib demonstrated potent antitumor activity in hedgehog-dependent tumors, particularly basal cell carcinomas. Clinically, phase I and II studies showed dramatic anticancer activity in patients with advanced basal cell carcinomas. In January 2012, vismodegib was approved by the FDA for the treatment of unresectable or metastatic basal cell carcinomas of the skin.

  16. The Inhibitory Effect of Salmon Calcitonin on Tri-Iodothyronine Induction of Early Hypertrophy in Articular Cartilage

    OpenAIRE

    Pingping Chen-An; Kim Vietz Andreassen; Kim Henriksen; Yadong Li; Morten Asser Karsdal; Anne-Christine Bay-Jensen

    2012-01-01

    OBJECTIVE: Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR) differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3)-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the ...

  17. Conjugation of salmon calcitonin to a combed-shaped end functionalized poly(poly(ethylene glycol) methyl ether methacrylate) yields a bioactive stable conjugate.

    Science.gov (United States)

    Ryan, Sinéad M; Wang, Xuexuan; Mantovani, Guiseppe; Sayers, Claire T; Haddleton, David M; Brayden, David J

    2009-04-02

    Salmon calcitonin (sCT) was conjugated via its N-terminal cysteine to a comb-shaped end-functionalized poly(poly(ethylene glycol) methyl ether methacrylate) (PolyPEG, 6.5 kDa), and to linear PEG (5 kDa). Conjugate molecular weight and purity was assessed by SEC-HPLC and MALDI-TOF MS. Bioactivity of conjugates was measured by cyclic AMP assay in T47D cells. Calcium and calcitonin levels were measured in rats following intravenous injections. Stability of conjugates was tested against serine proteases, intestinal and liver homogenates and serum. Cytotoxicity of conjugates was assessed by lactate dehydrogenase (LDH) assay and by haemolytic assay of rat red blood cells. Results showed that the two conjugates were of high purity with molecular weights similar to predictions. Both conjugates retained more than 85% bioactivity in vitro and had nanomolar EC(50) values similar to sCT. While both sCT-PolyPEG(6.5 K) and sCT-PEG(5 K) were resistant to metabolism by serine proteases, homogenates and serum, PolyPEG (6.5 K) was more so. Although both conjugates reduced serum calcium to levels similar to those achieved with sCT, PolyPEG(6.5 K) extended the T(1/2) and AUC of serum sCT over values achieved with sCT-PEG and sCT itself. None of PolyPEG, PEG or methacrylic acid displayed significant cytotoxicity. PolyPEG may therefore have potential to improve pharmacokinetic profiles of injected peptides.

  18. MAP kinase pathways and calcitonin influence CD44 alternate isoform expression in prostate cancer cells

    Directory of Open Access Journals (Sweden)

    Yang Kui

    2008-09-01

    Full Text Available Abstract Background Dysregulated expression and splicing of cell adhesion marker CD44 is found in many types of cancer. In prostate cancer (PC specifically, the standard isoform (CD44s has been found to be downregulated compared with benign tissue whereas predominant variant isoform CD44v7-10 is upregulated. Mitogen-activated protein kinase pathways and paracrine calcitonin are two common factors linked to dysregulated expression and splicing of CD44 in cancer. Calcitonin has been found to increase proliferation and invasion in PC acting through the protein kinase A pathway. Methods In androgen-independent PC with known high CD44v7-10 expression, CD44 total and CD44v7-10 RNA or protein were assessed in response to exogenous and endogenous calcitonin and to inhibitors of protein kinase A, MEK, JNK, or p38 kinase. Benign cells and calcitonin receptor-negative PC cells were also tested. Results MEK or p38 but not JNK reduced CD44 total RNA by 40%–65% in cancer and benign cells. Inhibition of protein kinase A reduced CD44 total and v7-10 protein expression. In calcitonin receptor-positive cells only, calcitonin increased CD44 variant RNA and protein by 3 h and persisting to 48 h, apparently dependent on an uninhibited p38 pathway. Cells with constitutive CT expression showed an increase in CD44v7-10 mRNA but a decrease in CD44 total RNA. Conclusion The MEK pathway increases CD44 RNA, while calcitonin, acting through the protein kinase A and p38 pathway, facilitates variant splicing. These findings could be used in the formulation of therapeutic methods for PC targeting CD44 alternate splicing.

  19. Calcitonin Receptor AluI (rs1801197) and Taq1 Calcitonin Genes Polymorphism in 45-and Over 45-year-old Women and their Association with Bone Density

    Science.gov (United States)

    Dehghan, Morteza; Pourahmad-Jaktaji, Razieh; Farzaneh, Zarghampoor

    2016-01-01

    Purpose: Calcitonin receptor gene has also a polymorphism which is associated with bone mass density. This study evaluates the association between calcitonin receptor AluI (rs1801197) and Taq1 calcitonin genes polymorphism with bone density rate. Methods: In this descriptive-analytical study in 2013 in southwestern Iran, 200 blood samples, per the Cochran sample size formula, were taken from women aged 45 and older. DNA was extracted from the samples using the phenol– chloroform method and the genomic fragments in question were proliferated using the polymerase chain reaction (PCR) method. Results: The genotypic distribution of polymorphism AluI for TT, TC, and CC genotypes in control group was 31.4%, 38.6%, and 30% and in patients 25.4%, 55.4%, and 19.2%, respectively. There was no significant difference in polymorphism AluI between patients and control group and no significant association was found between this gene and bone density rate (P > 0.05). All patients and the individuals in the control group exhibited tt genotype for TaqI calcitonin gene and no significant association was found between these participants and osteoporosis. Conclusion: There was no association between two polymorphisms and osteoporosis, and between polymorphism of these two genes and osteoporosis development rate in the participants. PMID:27708484

  20. CALCITONIN-LIKE IMMUNOREACTIVITY IN SERUM AND TISSUES OF THE BONNETHEAD SHARK, SPHYRNA TIBURO. (R826128)

    Science.gov (United States)

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  1. Eel calcitonin binding site distribution and antinociceptive activity in rats

    Energy Technology Data Exchange (ETDEWEB)

    Guidobono, F.; Netti, C.; Sibilia, V.; Villa, I.; Zamboni, A.; Pecile, A.

    1986-03-01

    The distribution of binding site for (/sup 125/I)-eel-calcitonin (ECT) to rat central nervous system, studied by an autoradiographic technique, showed concentrations of binding in the diencephalon, the brain stem and the spinal cord. Large accumulations of grains were seen in the hypothalamus, the amygdala, in the fasciculus medialis prosencephali, in the fasciculus longitudinalis medialis, in the ventrolateral part of the periventricular gray matter, in the lemniscus medialis and in the raphe nuclei. The density of grains in the reticular formation and in the nucleus tractus spinalis nervi trigemini was more moderate. In the spinal cord, grains were scattered throughout the dorsal horns. Binding of the ligand was displaced equally by cold ECT and by salmon CT(sCT), indicating that both peptides bind to the same receptors. Human CT was much weaker than sCT in displacing (/sup 125/I)-ECT binding. The administration of ECT into the brain ventricles of rats dose-dependently induced a significant and long-lasting enhancement of hot-plate latencies comparable with that obtained with sCT. The antinociceptive activity induced by ECT is compatible with the topographical distribution of binding sites for the peptide and is a further indication that fish CTs are active in the mammalian brain.

  2. Mucoadhesive intestinal devices for oral delivery of salmon calcitonin.

    Science.gov (United States)

    Gupta, Vivek; Hwang, Byeong Hee; Lee, Joohee; Anselmo, Aaron C; Doshi, Nishit; Mitragotri, Samir

    2013-12-28

    One of the major challenges faced by therapeutic polypeptides remains their invasive route of delivery. Oral administration offers a potential alternative to injections; however, this route cannot be currently used for peptides due to their limited stability in the stomach and poor permeation across the intestine. Here, we report mucoadhesive devices for oral delivery that are inspired by the design of transdermal patches and demonstrate their capabilities in vivo for salmon calcitonin (sCT). The mucoadhesive devices were prepared by compressing a polymeric matrix containing carbopol, pectin and sodium carboxymethylcellulose (1:1:2), and were coated on all sides but one with an impermeable and flexible ethyl cellulose (EC) backing layer. Devices were tested for in vitro dissolution, mucoadhesion to intestinal mucosa, enhancement of drug absorption in vitro (Caco-2 monolayer transport) and in vivo in rats. Devices showed steady drug release with ≈75% cumulative drug released in 5h. Devices also demonstrated strong mucoadhesion to porcine small intestine to withstand forces up to 100 times their own weight. sCT-loaded mucoadhesive devices exhibited delivery of sCT across Caco-2 monolayers and across the intestinal epithelium in vivo in rats. A ≈52-fold (pharmacokinetic) and ≈44-fold (pharmacological) enhancement of oral bioavailability was observed with mucoadhesive devices when compared to direct intestinal injections. Oral delivery of devices in enteric coated capsules resulted in significant bioavailability enhancement.

  3. Does salmon calcitonin cause cancer? A review and meta-analysis.

    Science.gov (United States)

    Wells, G; Chernoff, J; Gilligan, J P; Krause, D S

    2016-01-01

    Recently an association between the use of calcitonin and cancer has been postulated. We reviewed the biological rationale and performed an additional analysis of historical data with respect to the possibility. An association cannot be excluded, but the relationship is weak and causality is unlikely. The purpose of the present study is to review the strength of association and likelihood of a causal relationship between use of calcitonin and cancer. We reviewed the evidence for this association, including the molecular signaling mechanisms of calcitonin, preclinical data, an "experiment of nature," and the results of a previous meta-analysis which showed a weak association. We performed an additional meta-analysis to incorporate the data from a novel investigational oral formulation of salmon calcitonin. Review of the literature did not identify a cellular signaling mechanism of action which might account for a causal relationship or toxicologic or postmarketing data to support the thesis. Additional clinical results incorporated into previous meta-analyses weakened but did not completely negate the possibility of association. A causal association between calcitonin use and malignancy is unlikely, as there is little biological plausibility. The preponderance of nonclinical and clinical evidence also does not favor a causal relationship.

  4. Low cytotoxic elastic niosomes loaded with salmon calcitonin on human skin fibroblasts.

    Science.gov (United States)

    Manosroi, Aranya; Chankhampan, C; Ofoghi, H; Manosroi, W; Manosroi, J

    2013-01-01

    A low cytotoxic elastic niosomal formulation loaded with salmon calcitonin was developed. The elastic niosomes were prepared from Tween 61 mixed with cholesterol at various concentrations of the edge activators (sodium cholate (NaC) and sodium deoxycholate (NaDC); 0.25, 0.5, 2.5, 5 and 10% mole) or ethanol (10-30% v/v). The effects of the niosomal concentrations (5, 10 and 20 mM) and phosphate buffer at pH 7.0 (5, 10, 20 and 30 mM) on the physical characteristics of niosomes were investigated. The 5 mM elastic niosomes in 5 mM phosphate buffer containing calcitonin 0.22 mg/mL gave the highest elasticity (deformability index (DI)) at 6.79 ± 2.03 determined by the extrusion method. The blank elastic niosomes comprised 2.5% mole NaDC, 5% mole NaC or 20% v/v ethanol showed the highest elasticity. The 5% mole NaC elastic niosomes loaded with calcitonin gave the highest DI (21.59 ± 0.91) and percentages of calcitonin entrapment efficiency (60.11 ± 4.98). This study has demonstrated that this NaC elastic niosome did not only reduce the cytotoxicity of the loaded calcitonin but also gave superior cell viability to the ethanolic elastic niosome as well.

  5. Calcitonin and vitamin D3 have high therapeutic potential for improving diabetic mandibular growth

    Institute of Scientific and Technical Information of China (English)

    Mona A Abbassy; Ippei Watari; Ahmed S Bakry; Takashi Ono; Ali H Hassan

    2016-01-01

    The goal of this study was to assess the effect of the intermittent combination of an antiresorptive agent (calcitonin) and an anabolic agent (vitamin D3) on treating the detrimental effects of Type 1 diabetes mellitus (DM) on mandibular bone formation and growth. Forty 3-week-old male Wistar rats were divided into four groups: the control group (normal rats), the control C1D group (normal rats injected with calcitonin and vitamin D3), the diabetic C1D group (diabetic rats injected with calcitonin and vitamin D3) and the diabetic group (uncontrolled diabetic rats). An experimental DM condition was induced in the male Wistar rats in the diabetic and diabetic C1D groups using a single dose of 60 mg?kg–1 body weight of streptozotocin. Calcitonin and vitamin D3 were simultaneously injected in the rats of the control C1D and diabetic C1D groups. All rats were killed after 4 weeks, and the right mandibles were evaluated by micro-computed tomography and histomorphometric analysis. Diabetic rats showed a significant deterioration in bone quality and bone formation (diabetic group). By contrast, with the injection of calcitonin and vitamin D3, both bone parameters and bone formation significantly improved (diabetic C1D group) (P < 0.05). These findings suggest that these two hormones might potentially improve various bone properties.

  6. A randomized double-blind placebo-controlled trial to investigate the effects of nasal calcitonin on bone microarchitecture measured by high-resolution peripheral quantitative computerized tomography in postmenopausal women — Study protocol

    Directory of Open Access Journals (Sweden)

    Azria Moise

    2008-04-01

    Full Text Available Abstract Background Bone microarchitecture is a significant determinant of bone strength. So far, the assessment of bone microarchitecture has required bone biopsies, limiting its utilization in clinical practice to one single skeletal site. With the advance of high-resolution imaging techniques, non-invasive in vivo measurement of bone microarchitecture has recently become possible. This provides an opportunity to efficiently assess the effects of anti-osteoporotic therapies on bone microarchitecture. We therefore designed a protocol to investigate the effects of nasal salmon calcitonin, an inhibitor of osteoclast activity, on bone microarchitecture in postmenopausal women, comparing weight bearing and non-weight bearing skeletal sites. Methods One hundred postmenopausal women will be included in a randomized, placebo-controlled, double-blind trial comparing the effect of nasal salmon calcitonin (200 UI/day to placebo over two years. Bone microarchitecture at the distal radius and distal tibia will be determined yearly by high-resolution peripheral quantitative computerized tomography (p-QCT with a voxel size of 82 μm and an irradiation of less than 5 μSv. Serum markers of bone resorption and bone formation will be measured every 6 months. Safety and compliance will be assessed. Primary endpoint is the change in bone microarchitecture; secondary endpoint is the change in markers of bone turnover. Hypothesis The present study should provide new information on the mode of action of nasal calcitonin. We hypothezise that - compared to placebo - calcitonin impacts on microstructural parameters, with a possible difference between weight bearing and non-weight bearing bones. Trial Registration ClinicalTrials.gov NCT00372099

  7. Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats

    DEFF Research Database (Denmark)

    Feigh, M; Andreassen, K V; Neutzsky-Wulff, A V

    2012-01-01

    Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male Zucker diabetic fatty...... (ZDF) rats, a model of type 2 diabetes....

  8. Choosing the Right Basal Reader.

    Science.gov (United States)

    Robbins, Ruth H.

    1980-01-01

    Looks at factors in the textbook publishing industry, especially costs and censorship, which affect the quality of available reading series. Notes the problem of readability and content bias. Finally, presents a checklist of basal reader evaluation criteria. (SJL)

  9. Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes

    DEFF Research Database (Denmark)

    Sondergaard, B C; Wulf, H; Henriksen, K

    2006-01-01

    chain reaction (RT-PCR). In bovine articular cartilage explants, cartilage degradation was investigated by release of C-terminal telopeptides of collagen type II (CTX-II), induced by tumor necrosis factor-alpha (TNF-alpha) [20 ng/ml] and oncostatin M (OSM) [10 ng/ml], with salmon calcitonin [0.......0001-1 microM]. In vivo, cartilage degradation was investigated in ovariectomized (OVX) rats administered with oral calcitonin [2 mg/kg calcitonin] for 9 weeks. RESULTS: The calcitonin receptor was identified in articular chondrocytes by immunohistochemistry and RT-PCR. Calcitonin concentration......-dependently increased cAMP levels in isolated chondrocytes. Explants cultured with TNF-alpha and OSM showed a 100-fold increase in CTX-II release compared to vehicle-treated controls (Pprotection...

  10. Calcitonin plays a critical role in regulating skeletal mineral metabolism during lactation.

    Science.gov (United States)

    Woodrow, Janine P; Sharpe, Christopher J; Fudge, Neva J; Hoff, Ana O; Gagel, Robert F; Kovacs, Christopher S

    2006-09-01

    The maternal skeleton rapidly demineralizes during lactation to provide calcium to milk, responding to the stimuli of estrogen deficiency and mammary-secreted PTH-related protein. We used calcitonin/calcitonin gene-related peptide-alpha (Ctcgrp) null mice to determine whether calcitonin also modulates lactational mineral metabolism. During 21 d of lactation, spine bone mineral content dropped 53.6% in Ctcgrp nulls vs. 23.6% in wild-type (WT) siblings (P bone mineral content returned fully to baseline in 18.1 d in Ctcgrp null vs. 13.1 d in WT (P protect the maternal skeleton against excessive resorption and attendant fragility during lactation and reveal that the postweaning skeleton has the remarkable ability to rapidly recover even from losses of over 50% of skeletal mineral content.

  11. Quantitative Structure-Activity Relationships and Docking Studies of Calcitonin Gene-Related Peptide Antagonists

    DEFF Research Database (Denmark)

    Jenssen, Håvard; Mehrabian, Mohadeseh; Kyani, Anahita

    2012-01-01

    Defining the role of calcitonin gene-related peptide in migraine pathogenesis could lead to the application of calcitonin gene-related peptide antagonists as novel migraine therapeutics. In this work, quantitative structure-activity relationship modeling of biological activities of a large range...... of calcitonin gene-related peptide antagonists was performed using a panel of physicochemical descriptors. The computational studies evaluated different variable selection techniques and demonstrated shuffling stepwise multiple linear regression to be superior over genetic algorithm-multiple linear regression....... The linear quantitative structure-activity relationship model revealed better statistical parameters of cross-validation in comparison with the non-linear support vector regression technique. Implementing only five peptide descriptors into this linear quantitative structure-activity relationship model...

  12. The inhibitory effect of salmon calcitonin on tri-iodothyronine induction of early hypertrophy in articular cartilage.

    Directory of Open Access Journals (Sweden)

    Pingping Chen-An

    Full Text Available OBJECTIVE: Salmon calcitonin has chondroprotective effect both in vitro and in vivo, and is therefore being tested as a candidate drug for cartilage degenerative diseases. Recent studies have indicated that different chondrocyte phenotypes may express the calcitonin receptor (CTR differentially. We tested for the presence of the CTR in chondrocytes from tri-iodothyronin (T3-induced bovine articular cartilage explants. Moreover, investigated the effects of human and salmon calcitonin on the explants. METHODS: Early chondrocyte hypertrophy was induced in bovine articular cartilage explants by stimulation over four days with 20 ng/mL T3. The degree of hypertrophy was investigated by molecular markers of hypertrophy (ALP, IHH, COLX and MMP13, by biochemical markers of cartilage turnover (C2M, P2NP and AGNxII and histology. The expression of the CTR was detected by qPCR and immunohistochemistry. T3-induced explants were treated with salmon or human calcitonin. Calcitonin down-stream signaling was measured by levels of cAMP, and by the molecular markers. RESULTS: Compared with untreated control explants, T3 induction increased expression of the hypertrophic markers (p<0.05, of cartilage turnover (p<0.05, and of CTR (p<0.01. Salmon, but not human, calcitonin induced cAMP release (p<0.001. Salmon calcitonin also inhibited expression of markers of hypertrophy and cartilage turnover (p<0.05. CONCLUSIONS: T3 induced early hypertrophy of chondrocytes, which showed an elevated expression of the CTR and was thus a target for salmon calcitonin. Molecular marker levels indicated salmon, but not human, calcitonin protected the cartilage from hypertrophy. These results confirm that salmon calcitonin is able to modulate the CTR and thus have chondroprotective effects.

  13. Quality analysis of salmon calcitonin in a polymeric bioadhesive pharmaceutical formulation: sample preparation optimization by DOE.

    Science.gov (United States)

    D'Hondt, Matthias; Van Dorpe, Sylvia; Mehuys, Els; Deforce, Dieter; DeSpiegeleer, Bart

    2010-12-01

    A sensitive and selective HPLC method for the assay and degradation of salmon calcitonin, a 32-amino acid peptide drug, formulated at low concentrations (400 ppm m/m) in a bioadhesive nasal powder containing polymers, was developed and validated. The sample preparation step was optimized using Plackett-Burman and Onion experimental designs. The response functions evaluated were calcitonin recovery and analytical stability. The best results were obtained by treating the sample with 0.45% (v/v) trifluoroacetic acid at 60 degrees C for 40 min. These extraction conditions did not yield any observable degradation, while a maximum recovery for salmon calcitonin of 99.6% was obtained. The HPLC-UV/MS methods used a reversed-phase C(18) Vydac Everest column, with a gradient system based on aqueous acid and acetonitrile. UV detection, using trifluoroacetic acid in the mobile phase, was used for the assay of calcitonin and related degradants. Electrospray ionization (ESI) ion trap mass spectrometry, using formic acid in the mobile phase, was implemented for the confirmatory identification of degradation products. Validation results showed that the methodology was fit for the intended use, with accuracy of 97.4+/-4.3% for the assay and detection limits for degradants ranging between 0.5 and 2.4%. Pilot stability tests of the bioadhesive powder under different storage conditions showed a temperature-dependent decrease in salmon calcitonin assay value, with no equivalent increase in degradation products, explained by the chemical interaction between salmon calcitonin and the carbomer polymer.

  14. Type II Turn of Receptor-bound Salmon Calcitonin Revealed by X-ray Crystallography.

    Science.gov (United States)

    Johansson, Eva; Hansen, Jakob Lerche; Hansen, Ann Maria Kruse; Shaw, Allan Christian; Becker, Peter; Schäffer, Lauge; Reedtz-Runge, Steffen

    2016-06-24

    Calcitonin is a peptide hormone consisting of 32 amino acid residues and the calcitonin receptor is a Class B G protein-coupled receptor (GPCR). The crystal structure of the human calcitonin receptor ectodomain (CTR ECD) in complex with a truncated analogue of salmon calcitonin ([BrPhe(22)]sCT(8-32)) has been determined to 2.1-Å resolution. Parallel analysis of a series of peptide ligands showed that the rank order of binding of the CTR ECD is identical to the rank order of binding of the full-length CTR, confirming the structural integrity and relevance of the isolated CTR ECD. The structure of the CTR ECD is similar to other Class B GPCRs and the ligand binding site is similar to the binding site of the homologous receptors for the calcitonin gene-related peptide (CGRP) and adrenomedulin (AM) recently published (Booe, J. M., Walker, C. S., Barwell, J., Kuteyi, G., Simms, J., Jamaluddin, M. A., Warner, M. L., Bill, R. M., Harris, P. W., Brimble, M. A., Poyner, D. R., Hay, D. L., and Pioszak, A. A. (2015) Mol. Cell 58, 1040-1052). Interestingly the receptor-bound structure of the ligand [BrPhe(22)]sCT(8-32) differs from the receptor-bound structure of the homologous ligands CGRP and AM. They all adopt an extended conformation followed by a C-terminal β turn, however, [BrPhe(22)]sCT(8-32) adopts a type II turn (Gly(28)-Thr(31)), whereas CGRP and AM adopt type I turns. Our results suggest that a type II turn is the preferred conformation of calcitonin, whereas a type I turn is the preferred conformation of peptides that require RAMPs; CGRP, AM, and amylin. In addition the structure provides a detailed molecular explanation and hypothesis regarding ligand binding properties of CTR and the amylin receptors.

  15. A phase 3 trial of the efficacy and safety of oral recombinant calcitonin: the Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) trial.

    Science.gov (United States)

    Binkley, Neil; Bolognese, Michael; Sidorowicz-Bialynicka, Anna; Vally, Tasneem; Trout, Richard; Miller, Colin; Buben, Christine E; Gilligan, James P; Krause, David S

    2012-08-01

    The Oral Calcitonin in Postmenopausal Osteoporosis (ORACAL) study was a randomized, double-blind, double-dummy, active- and placebo-controlled, multiple-dose, phase 3 study to assess the efficacy and safety of oral recombinant calcitonin for treatment of postmenopausal osteoporosis. A total of 565 women age 46 to 86 (mean 66.5) years were randomized (4:3:2) to receive oral recombinant salmon calcitonin (rsCT) tablets (0.2  mg/d) plus placebo nasal spray, synthetic salmon calcitonin (ssCT) nasal spray (200 IU/d) plus placebo tablets, or placebo (placebo tablets plus placebo nasal spray), respectively for 48 weeks. All women received calcium (≥1000  mg/d) and vitamin D (800 IU/d). Women randomized to oral rsCT had a mean ± SD percent increase from baseline in lumbar spine bone mineral density (BMD) (1.5% ± 3.2%) that was greater than those randomized to ssCT nasal spray (0.78% ± 2.9%) or placebo (0.5% ± 3.2%). Lumbar spine BMD change in those receiving nasal calcitonin did not differ from placebo. Oral rsCT treatment also resulted in greater improvements in trochanteric and total proximal femur BMD than ssCT nasal spray. Reductions in bone resorption markers with oral rsCT were greater than those observed in ssCT nasal spray or placebo recipients. Approximately 80% of subjects in each treatment group experienced an adverse event, the majority of which were mild or moderate in intensity. Gastrointestinal system adverse events were reported by nearly one-half of women in all treatment groups and were the principal reason for premature withdrawals. Less than 10% of women experienced a serious adverse event and no deaths occurred. Overall, oral rsCT was superior to nasal ssCT and placebo for increasing BMD and reducing bone turnover. Oral rsCT was safe and as well tolerated as ssCT nasal spray or placebo. Oral calcitonin may provide an additional treatment alternative for women with postmenopausal osteoporosis.

  16. In vitro and in vivo characterisation of a novel peptide delivery system: amphiphilic polyelectrolyte-salmon calcitonin nanocomplexes.

    Science.gov (United States)

    Cheng, Woei-Ping; Thompson, Colin; Ryan, Sinéad M; Aguirre, Tanira; Tetley, Laurence; Brayden, David J

    2010-10-15

    The cationic peptide, salmon calcitonin (sCT) was complexed with the cationic amphiphilic polyelectrolyte, poly(allyl)amine, grafted with palmitoyl and quaternary ammonium moieties at pH 5.0 and 7.4 to yield particulates (sCT-QPa). The complexes were approximately 200 nm in diameter, had zeta potentials ranging from +20 to +50 mV, and had narrow polydispersity indices (PDIs). Differential scanning calorimetry revealed the presence of an interaction between sCT and QPa in the complexes. Electron microscopy confirmed the zeta-size data and revealed a vesicular bilayer structure with an aqueous core. Tyrosine- and Nile red fluorescence indicated that the complexes retained gross physical stability for up to 7 days, but that the pH 5.0 complexes were more stable. The complexes were more resistant to peptidases, serum and liver homogenates compared to free sCT. In vitro bioactivity was measured by cAMP production in T47D cells and the complexes had EC50 values in the nM range. While free sCT was unable to generate cAMP following storage for 7 days, the complexes retained approximately 33% activity. When the complexes were injected intravenously to rats, free and complexed sCT (pH 5.0 and 7.4) but not QPa reduced serum calcium over 120 min. Free and complexed sCT but not QPa also reduced serum calcium over 240 min following intra-jejunal administration. In conclusion, sCT-QPa nanocomplexes that have been synthesised are stable, bioactive and resistant to a range of peptidases. These enhanced features suggest that they may have the potential for improved efficacy when formulated for injected and oral delivery.

  17. Evaluation of bone targeting salmon calcitonin analogues in rats developing osteoporosis and adjuvant arthritis.

    Science.gov (United States)

    Bhandari, Krishna H; Asghar, Waheed; Newa, Madhuri; Jamali, Fakhreddin; Doschak, Michael R

    2015-01-01

    Synthetic analogues of the peptide hormone calcitonin have been used in medicine as biologic drug therapies for decades, to treat pathological conditions of excessive bone turnover, such as osteoporosis, where more bones are removed than replaced during bone remodeling. Osteoporosis and other chronic skeletal diseases, including inflammatory arthritis, exact a substantial and growing toll on aging populations worldwide however they respond poor to synthetic biologic drug therapy, due in part to the rapid half-life of elimination, which for calcitonin is 43 minutes. To address those shortcomings, we have developed and synthesized bone-targeting variants of calcitonin as a targeted drug delivery strategy, by conjugation to bisphosphonate drug bone-seeking functional groups in highly specific reaction conditions. To evaluate their in vivo efficacy, bisphosphonate-mediated bone targeting with PEGylated (polyethylene glycol conjugated) and non-PEGylated salmon calcitonin analogues were synthesized and dose escalation was performed in female rats developing Osteoporosis. The bone-targeting calcitonin analogues were also tested in a separate cohort of male rats developing adjuvant-induced arthritis. Ovariectomized female rats developing Osteoporosis were administered daily sub-cutaneous injection of analogues equivalent to 5, 10 and 20 IU/kg of calcitonin for 3 months. Adjuvant arthritis was developed in male rats by administering Mycobacterium butyricum through tail base injection. Daily sub-cutaneous injection of analogues equivalent to 20 IU/kg of calcitonin was administered and the rats were measured for visible signs of inflammation to a 21 day endpoint. In both studies, the effect of drug intervention upon bone volume and bone mineral density (BMD) was assessed by measuring the trabecular bone volume percentage and BMD at the proximal tibial metaphysis using in vivo micro-computed tomography. With dose escalation studies, only bone targeting analogue dosed groups

  18. An immunohistochemical study of the antinociceptive effect of calcitonin in ovariectomized rats

    Directory of Open Access Journals (Sweden)

    Sekiguchi Miho

    2008-12-01

    Full Text Available Abstract Background Calcitonin is used as a treatment to reduce the blood calcium concentration in hypercalcemia and to improve bone mass in osteoporosis. An analgesic effect of calcitonin has been observed and reported in clinical situations. Ovariectomaized (OVX rats exhibit the same hormonal changes as observed in humans with osteoporosis and are an animal model of postmenopousal osteoporosis. The aim of this study to investigate antinociceptive effect of calcitonin in OVX rats using the immunohistochemical study. Methods We assessed the antinociceptive effects of calcitonin in an ovariectomized (OVX rat model, which exhibit osteoporosis and hyperalgesia, using the immunohistochemical method. Fifteen rats were ovariectomized bilaterally, and ten rats were received the same surgery expected for ovariectomy as a sham model. We used five groups: the OVX-CT (n = 5, the sham-CT (n = 5, and the OVX-CT-pcpa (n = 5 groups recieved calcitonin (CT: 4 U/kg/day, while OVX-vehi (n = 5 and the sham-vehi (n = 5 groups received vehicle subcutaneously 5 times a week for 4 weeks. The OVX-CT-pcpa-group was given traperitoneal injection of p-chlorophenylalanine (pcpa; an inhibitor of serotonin biosynthesis (100 mg/kg/day in the last 3 days of calcitonon injection. Two hours after 5% formalin (0.05 ml subcutaneously into the hind paw, the L5 spinal cord were removed and the number of Fos-immunoreactive (ir neurons were evaluated using the Mann-Whitney-U test. Results The numbers of Fos-ir neurons in the OVX-CT and sham-CT groups were significantly less than in the OVX-vehi and sham-vehi groups, respectively (p = 0.0090, p = 0.0090. The number of Fos-ir neurons in the OVX-CT-pcpa-group was significantly more than that of the OVX-CT-group (p = 0.0283, which means pcpa inhibits calcitonin induced reduction of c-Fos production. Conclusion The results in this study demonstrated that 1 the increase of c-Fos might be related to hyperalgesia in OVX-rats. 2 Calcitonin has

  19. [Rational (injection) of calcitonin for stimulation of the mandibular reparative regeneration].

    Science.gov (United States)

    Shvyrkov, M B

    2011-01-01

    This investigation permit to detect, that first resorption stage of the mandible reparative regeneration terminats after fracture 5 days later. Calcitonine injection during 5 days after fracture i.e. in paratiroid hormone dependent stage distorts normal reparative process. Rats with traumatic osteomielitis become 1.5 times more and rats with normal regeneration become 3 times less. Injection calcitonine in KT-dependent stage, i.e. in 6-11 days after fracture increases quantity of rats with normal regeneration in 7 times and decreases quantity animals with traumatic osteomielitis on 50%. There's recommendation to inject KT from 6 days after trauma.

  20. Differential localization and characterization of functional calcitonin gene-related peptide receptors in human subcutaneous arteries

    DEFF Research Database (Denmark)

    Edvinsson, L; Ahnstedt, H; Larsen, R;

    2014-01-01

    Calcitonin gene-related peptide (CGRP) and its receptor are widely distributed within the circulation and the mechanism behind its vasodilation not only differs from one animal species to another but is also dependent on the type and size of vessel. The present study examines the nature of CGRP......-induced vasodilation, characteristics of the CGRP receptor antagonist telcagepant and localization of the key components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) of the CGRP receptor in human subcutaneous arteries....

  1. Calcitonin Gene-Related Peptide in Tension-Type Headache

    Directory of Open Access Journals (Sweden)

    M. Ashina

    2002-01-01

    Full Text Available In the last 10 years there has been increasing interest in the role of calcitonin gene-related peptide (CGRP in primary headaches. Tension-type headache is one of the most common and important types of primary headaches, and ongoing nociception from myofascial tissues may play an important role in the pathophysiology of this disorder. CGRP sensory fibers are preferentially located in the walls of arteries, and nerve fibers containing CGRP accompany small blood vessels in human cranial muscles. It is well established that nociception may lead to release of CGRP from sensory nerve endings and from central terminals of sensory afferents into the spinal cord. It has also been shown that density of CGRP fibers around arteries is increased in persistently inflamed muscle. These findings indicate that ongoing activity in sensory neurons in the cranial muscles may be reflected in changes of plasma levels of neuropeptides in patients with chronic tension-type headache. To explore the possible role of CGRP in tension-type headache, plasma levels of CGRP were measured in patients with chronic tension-type headache. This study showed that plasma levels of CGRP are normal in patients and unrelated to headache state. However, the findings of normal plasma levels of CGRP do not exclude the possibility that abnormalities of this neuropeptide at the neuronal or peripheral (pericranial muscles levels play a role in the pathophysiology of tension-type headache. Investigation of CGRP in other compartments with new sensitive methods of analysis is necessary to clarify its role in tension-type headache.

  2. Expression of a chimeric human/salmon calcitonin gene integrated into the Saccharomyces cerevisiae genome using rDNA sequences as recombination sites.

    Science.gov (United States)

    Sun, Hengyi; Zang, Xiaonan; Liu, Yuantao; Cao, Xiaofei; Wu, Fei; Huang, Xiaoyun; Jiang, Minjie; Zhang, Xuecheng

    2015-12-01

    Calcitonin participates in controlling homeostasis of calcium and phosphorus and plays an important role in bone metabolism. The aim of this study was to endow an industrial strain of Saccharomyces cerevisiae with the ability to express chimeric human/salmon calcitonin (hsCT) without the use of antibiotics. To do so, a homologous recombination plasmid pUC18-rDNA2-ura3-P pgk -5hsCT-rDNA1 was constructed, which contains two segments of ribosomal DNA of 1.1 kb (rDNA1) and 1.4 kb (rDNA2), to integrate the heterologous gene into host rDNA. A DNA fragment containing five copies of a chimeric human/salmon calcitonin gene (5hsCT) under the control of the promoter for phosphoglycerate kinase (P pgk ) was constructed to express 5hsCT in S. cerevisiae using ura3 as a selectable auxotrophic marker gene. After digestion by restriction endonuclease HpaI, a linear fragment, rDNA2-ura3-P pgk -5hsCT-rDNA1, was obtained and transformed into the △ura3 mutant of S. cerevisiae by the lithium acetate method. The ura3-P pgk -5hsCT sequence was introduced into the genome at rDNA sites by homologous recombination, and the recombinant strain YS-5hsCT was obtained. Southern blot analysis revealed that the 5hsCT had been integrated successfully into the genome of S. cerevisiae. The results of Western blot and ELISA confirmed that the 5hsCT protein had been expressed in the recombinant strain YS-5hsCT. The expression level reached 2.04 % of total proteins. S. cerevisiae YS-5hsCT decreased serum calcium in mice by oral administration and even 0.01 g lyophilized S. cerevisiae YS-5hsCT/kg decreased serum calcium by 0.498 mM. This work has produced a commercial yeast strain potentially useful for the treatment of osteoporosis.

  3. Iodine-123 salmon calcitonin, an imaging agent for calcitonin receptors: synthesis, biodistribution, metabolism and dosimetry in humans

    Energy Technology Data Exchange (ETDEWEB)

    Blower, P.J.; Kettle, A.G.; Leak, A.; O`Doherty, M.J. [Department of Nuclear Medicine, Kent and Canterbury Hospital, Canterbury (United Kingdom); Puncher, M.R.B.; George, S.; Dorsch, S.; Naylor, L.H. [Department of Biosciences, University of Kent, Canterbury (United Kingdom)

    1998-02-01

    A modified chloramine-T method was used to label a pharmaceutical form of salmon calcitonin (SCT) with iodine-123. Labelling can be performed within 5 min including purification, resulting in >95% radiochemical purity and 70% yield. Digestion analysis shows labelling with two iodine atoms on the tyrosine residue. A Chinese hamster ovary cell-based assay showed that the receptor binding and activation were not impaired by the labelling. Biodistribution in mice was similar to that of commercially available mono-iodinated {sup 125}I-labelled SCT, kidney being the principal target organ. Evaluation in three patients previously diagnosed as having Paget`s disease (injected with 37 MBq [{sup 123}I]diiodotyrosyl{sup 22}-SCT, containing less than 4 IU hormone, imaged dynamically up to 0.5 h and at intervals up to 24 h) shows early uptake in liver, kidney and sites of known Paget`s disease but not in normal bone, and later uptake in thyroid and stomach. Blood clearance was fitted to a biexponential with half-lives of 3.4-7.4 min and 3-34 h. Radiation dosimetry was estimated using MIRDOSE 3. The highest doses (mean mGy/MBq) were to thyroid (6.8 x 10{sup -1}) and kidney (6.0 x 10{sup -2}), with a whole-body dose 3.0 x 10{sup -2}. High performance liquid chromatography analysis revealed that urinary radioactivity was mostly in the form of iodide and diiodotyrosine within minutes of injection, indicating rapid in vivo breakdown.(orig. /MG) (orig.) With 8 figs., 1 tab., 28 refs.

  4. C-cell-derived calcitonin-free neuroendocrine carcinoma of the thyroid: the diagnostic importance of CGRP immunoreactivity.

    Science.gov (United States)

    Nakazawa, Tadao; Cameselle-Teijeiro, José; Vinagre, João; Soares, Paula; Rousseau, Emmanuel; Eloy, Catarina; Sobrinho-Simões, Manuel

    2014-09-01

    In the thyroid, primary neuroendocrine tumors encompass medullary thyroid carcinoma (MTC) and, rarely, other tumors such as paragangliomas. MTCs are derived from C-cells and express calcitonin and neuroendocrine markers. Besides classic MTC, some reports have documented thyroid neuroendocrine tumors, which show no calcitonin expression and raise difficult diagnostic problems. A 76-year-old man presented with a mass in the left thyroid with neither serological calcitonin elevation nor familial history. A thorough clinico-laboratorial study did not disclose any other mass elsewhere. A left hemithyroidectomy was performed, and the histological examination revealed a neuroendocrine carcinoma resembling a paraganglioma-like MTC displaying unequivocal signs of vascular invasion. Immunohistochemically, the tumor cells showed reactivity for chromogranin A, synaptophysin, thyroid transcription factor-1 (TTF-1), paired box gene 8 (PAX8), cytokeratins (AE1/AE3 and CK8/18), and calcitonin gene-related peptide (CGRP) and negativity for calcitonin, carcinoembryonic antigen, TTF-2, thyroperoxidase, and thyroglobulin. In situ hybridization showed that the tumor cells lacked expression for calcitonin and thyroglobulin mRNA. Genetic analysis did not disclose any RET mutation. A diagnosis of C-cell-derived primary neuroendocrine carcinoma of the thyroid without calcitonin expression was made, and the patient remains free of metastasis or recurrence 18 months after surgery.

  5. Nevoid basal cell carcinoma syndrome

    Directory of Open Access Journals (Sweden)

    Kannan Karthiga

    2006-01-01

    Full Text Available Binkley and Johnson first reported this syndrome in 1951. But it was in 1960, Gorlin-Goltz established the association of basal cell epithelioma, jaw cyst and bifid ribs, a combination which is now frequently known as Gorlin-Goltz syndrome as well as Nevoid Basal Cell Carcinoma Syndrome (NBCCS. NBCCS is inherited as an autosomal dominant trait with high penetrance and variable expressivity. NBCCS is characterized by variety of cutaneous, dental, osseous, opthalmic, neurologic and sexual abnormalities. One such case of Gorlin-Goltz syndrome is reported here with good illustrations.

  6. VIP and Calcitonin-Producing Pancreatic Neuroendocrine Tumor with Watery Diarrhea: Clinicopathological Features and the Effect of Somatostatin Analogue

    Directory of Open Access Journals (Sweden)

    Tomoya Kon

    2012-03-01

    Full Text Available Context Pancreatic neuroendocrine tumor (pNET secretes various peptide hormones; however, calcitonin hypersecretion is rare. Its clinicopathological significance and treatment is still controversial. Case report A 43 year-old Japanese man presented severe watery diarrhea and a large mass in the pancreatic tail. Blood concentration of VIP was elevated to 649 pg/mL (reference range: 0- 100 pg/mL, and calcitonin to 66,700 pg/mL (reference range: 15-86 pg/mL. There was no tumor in other endocrine organs. The resected tumor was composed of 80% calcitonin-positive cells and 10% VIP-positive cells. After the operation, the levels of VIP and calcitonin were decreased to 44 and 553 pg/mL, respectively, and diarrhea was improved. The mRNA of somatostatin receptor (SSTR subtypes 2, 3 and 5 in the tumor tissue were increased 22.8, 25.1, and 37.0-fold of those of normal pancreas, respectively. At 19 months after the operation, blood calcitonin was again raised to 3,980 pg/mL, and metastatic tumors were found in the liver. With the treatment of long-acting somatostatin analogue, calcitonin was reduced to 803 pg/mL. The patient does not present endocrine symptom, and the size of the metastatic tumors appears stable. Conclusion From the world literature to date, co-secretion of VIP and calcitonin was documented in only 10 cases of pNET including the current case. Although VIP is a primary cause of diarrhea in these cases, high level of calcitonin may also influence on the clinical symptoms. Somatostatin analogue suppresses the levels of VIP and calcitonin, and the control proliferation is also expected when tumor cells express SSTRs.

  7. Acute effects of nasal salmon calcitonin on calcium and bone metabolism

    DEFF Research Database (Denmark)

    Thamsborg, G; Skousgaard, S G; Daugaard, H;

    1993-01-01

    Effects of a single dose of 200 IU of nasal salmon calcitonin (SCT) on calcium metabolism and biochemical markers of bone turnover were investigated in 12 healthy male volunteers in a randomized, placebo-controlled, cross-over design. The nasal spray was given in the morning, and subsequently blood...

  8. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement

    DEFF Research Database (Denmark)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon;

    2015-01-01

    hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate...

  9. Iontophoresis significantly increases the trans-dentinal delivery of osteoprotegerin, alendronate, and calcitonin.

    Science.gov (United States)

    Kitchens, James A; Schwartz, Scott A; Schindler, William G; Hargreaves, Kenneth M

    2007-10-01

    The purpose of this study was to evaluate the delivery of alendronate, calcitonin, and osteoprotegerin (OPG) through human dentin by both diffusion and iontophoresis for the potential treatment of invasive cervical resorption. Radiolabeled alendronate, calcitonin, and OPG were added to the top of a split chamber device that contained 1-mm thick dentin disks devoid of a smear layer. Transdentinal movement of medicaments by either random diffusion or application of an iontophoretic current was measured by analysis of gamma emission of effluent fractions. In addition, calcitonin delivery was evaluated at differing magnitudes of current (0-4 mA) by using the aforementioned chamber. Diffusion of all 3 medicaments was minimal. In contrast, the application of a 3-mA iontophoretic gradient significantly increased delivery for all 3 compounds at 10-, 20-, and 30-minute intervals. In addition, a linear increase in permeability was seen for calcitonin as milliamperes were increased from 0 to 4 (r = 0.947), with more than a 100-fold increase in delivery observed with iontophoresis. Delivery of the tested medicaments by using iontophoresis might prove to be a useful technique for treatment of invasive cervical resorption.

  10. Effect of the calcitonin gene-related peptide (CGRP) receptor antagonist telcagepant in human cranial arteries

    NARCIS (Netherlands)

    L. Edvinsson (Lars); K.Y. Chan (Kayi); S. Eftekhari; E. Nilsson (Elisabeth); R. de Vries (René); H. Säveland (Hans); C.M.F. Dirven (Clemens); A.H.J. Danser (Jan)

    2010-01-01

    textabstractIntroduction: Calcitonin gene-related peptide (CGRP) is a neuronal messenger in intracranial sensory nerves and is considered to play a significant role in migraine pathophysiology. Materials and methods: We investigated the effect of the CGRP receptor antagonist, telcagepant, on CGRP-in

  11. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine-...

  12. Value of anti- Müllerian hormone serum concentrations of basal and day 6 after stimulation as predictors of ovarian response%基础及促性腺激素刺激第6天血清抗苗勒管激素水平对卵巢反应性的预测价值

    Institute of Scientific and Technical Information of China (English)

    杨晓菁; 林文琴; 余蓉

    2012-01-01

    (group B, w=50) , and over response (group C, n = 30) based on the number of oocytes retrieved and serum levels of E2 on hCG administration day. The serum levels of FSH, estradiol (E2) at baseline, anti-Miillerian hormone (AMH) at baseline and on day 6 after stimulation (D6AMH) , E2 on day 6 after stimulation (D6E2)and on hCG administration day, and the number of antral follicle count (AFC) were assessed. Ovarian response was evaluated by the number of oocytes retrieved. Results: The levels of AMH at baseline and day 6, the number of oocytes retrieved and the levels of E2 on hCG day had statistically significant differences among the three groups ( group C>group B> group A, P<0. 05). The serum levels of AMH at baseline and on day 6 after stimulation were significantly different in all three groups(P<0. 05). Serum levels of AMH 6 days after stimulation were significantly lower than those at baseline (P<0. 05). The number of oocytes retrieved was strongly correlated with the level of D6AMH, D6E2, the level of AMH at baseline and AFC. The results of multiple regression analysis showed that D6AMH was the most important factor in predicting the number of retrieved oocytes. ROC analyses showed that D6AMH had the largest area under curve (AUC) 0. 872 to predict the poor response, when 1. 159 ng/ml was selected as the AMH cut-off value with 90% sensitivity and 84% specificity. To predict the high response, D6AMH had the largest area under curve (AUC) 0. 895, when 3. 22 ng/ml was selected as the AMH cut-off value with 77% sensitivity and 87% specificity. Conclusions: The AMH levels at basal and on day 6 after stimulation were both useful factors in predicting ovarian response and number of retrieved oocytes. The serum levels of AMH on 6 days after stimulation was highly correlated with the number of oocytes retrieved; therefore it could be a better predictor of ovarian response in IVF-ET.

  13. Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis.

    Science.gov (United States)

    Tafazal, Suhayl I; Ng, Leslie; Sell, Philip

    2007-02-01

    This is a double blind randomised controlled trial to assess the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis. The trial compared the outcome of salmon calcitonin nasal spray to placebo nasal spray in patients with MRI confirmed lumbar spinal stenosis. Lumbar spinal stenosis is one of the commonest conditions encountered by spine surgeons. It more frequently affects elderly patients and lumbar decompression has been used to treat the condition with variable success. Non operative measures have been investigated, but their success ranges from 15% to 43% in patients followed up for 1-5 years (Simotas in Clin Orthop 1(384):153-161, 2001). Salmon calcitonin injections have been investigated in previous trials and may have a treatment effect. Nasal salmon calcitonin has become available and if effective would have advantages over injections. Forty patients with symptoms of neurogenic claudication and MRI proven lumbar spinal stenosis were randomly assigned either nasal salmon calcitonin or placebo nasal spray to use for 4 weeks. This was followed by a 'washout' period of 6 weeks, and subsequent treatment with 6 weeks of nasal salmon calcitonin. Standard spine outcome measures including Oswestry disability index (ODI), low back outcome score, visual analogue score and shuttle walking test were administered at baseline, 4, 10 and 16 weeks. Twenty patients received nasal salmon calcitonin and twenty patients received placebo nasal spray. At 4 weeks post treatment there was no statistically significant difference in the outcome measures between the two groups. The change in ODI was a mean 1.3 points for the calcitonin group and 0.6 points for the placebo group (P = 0.51), the mean change in visual analogue score for leg pain was 10 mm in the calcitonin group and 0 mm in the placebo group (P = 0.51). There was no significant difference in walking distance between the two groups, with a mean improvement in walking distance of 21 m in the

  14. Cryotherapy in basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sandra A

    1999-01-01

    Full Text Available Cryotherapy has proved to be an effective tool in the management of various dermatoses. We report 6 patients with histopathologically proven basal cell carcinoma of variable sizes treated with liquid nitrogen cryotherapy by the open spray technique. Lesions tended to heal with depigmentation and scar formation. However depigmented areas often repigmented over a period of time.

  15. Salmon calcitonin reduces food intake through changes in meal sizes in male rhesus monkeys.

    Science.gov (United States)

    Bello, Nicholas T; Kemm, Matthew H; Moran, Timothy H

    2008-07-01

    Amylinergic mechanisms are believed to be involved in the control of appetite. This study examined the effects of the amylin agonist, salmon calcitonin, on food intake and meal patterns in adult male rhesus monkeys. Fifteen minutes before the onset of their 6-h daily feeding period, monkeys received intramuscular injections of various doses of salmon calcitonin (0.032, 0.056, 0.1, 0.32, and 1 microg/kg) or saline. Salmon calcitonin dose dependently reduced total daily and hourly food intake, with significant decreases at the 0.1, 0.32, and 1 microg/kg doses. Daily food intake was reduced by approximately 35%, 62%, and 96%, at these doses, respectively. An analysis of meal patterns revealed that size of the first meal was significantly reduced across the dose range of 0.056 to 1 microg/kg, while average meal size was reduced with the 0.32 and 1 microg/kg doses. Meal number was only affected at the 1 microg/kg dose. Repeated 5-day administration of the 0.1 microg/kg dose resulted in a reduction in daily food intake only on injection day 2, while significant reductions in food intake were observed on all five injection days with a 0.32 microg/kg dose. Daily food intake was also reduced for 1 day after the termination of the 5-day injections of the 0.32 microg/kg salmon calcitonin dose. These sustained reductions in intake were expressed through decreases in meal size. These data demonstrate that salmon calcitonin acutely and consistently decreases food intake mainly through reductions in meal sizes in nonhuman primates.

  16. Impact of congenital calcitonin deficiency due to dysgenetic hypothyroidism on bone mineral density

    Directory of Open Access Journals (Sweden)

    Daripa M.

    2004-01-01

    Full Text Available The objective of the present study was to determine the effect of chronic calcitonin deficiency on bone mass development. The results of 11 patients with thyroid dysgenesis (TD were compared to those of 17 normal individuals (C and of 9 patients with other forms of hypothyroidism (OH: 4 with hypothyroidism due to inborn errors of thyroid hormone synthesis and 5 with Hashimoto's thyroiditis. The subjects received an intravenous calcium stimulus and blood was collected for the determination of ionized calcium (Ca2+, calcitonin, and intact parathyroid hormone. Bone mineral density (BMD was determined by dual-energy X-ray absorptiometry. After calcium administration the levels of Ca2+ in the two groups of hypothyroidism were significantly higher than in the normal control group (10 min after starting calcium infusion: C = 1.29 ± 0.08 vs TD = 1.34 ± 0.03 vs OH = 1.34 ± 0.02 mmol/l; P < 0.05, and only the TD group showed no calcitonin response (5 min after starting calcium infusion: C = 27.9 ± 5.8 vs TD = 6.6 ± 0.3 vs OH = 43.0 ± 13.4 ng/l. BMD values did not differ significantly between groups (L2-L4: C = 1.116 ± 0.02 vs TD = 1.109 ± 0.03 vs OH = 1.050 ± 0.04 g/cm². These results indicate that early deficiency of calcitonin secretion has no detrimental effect on bone mass development. Furthermore, the increased calcitonin secretion observed in patients with inborn errors of thyroid hormone biosynthesis does not confer any advantage in terms of BMD.

  17. Calcitonin gene-related peptide induced migraine attacks in patients with and without familial aggregation of migraine

    DEFF Research Database (Denmark)

    Guo, Song; Christensen, Anne Francke; Liu, Marie Louise

    2017-01-01

    BACKGROUND: Calcitonin gene-related peptide provokes migraine attacks in 65% of patients with migraine without aura. Whether aggregation of migraine in first-degree relatives (family load) or a high number of risk-conferring single nucleotide polymorphisms contributes to migraine susceptibility...... to calcitonin gene-related peptide infusion in migraine patients is unknown. We hypothesized that genetic enrichment plays a role in triggering of migraine and, therefore, migraine without aura patients with high family load would report more migraine attacks after calcitonin gene-related peptide infusion than...... patients with low family load. METHODS: We allocated 40 previously genotyped migraine without aura patients to receive intravenous infusion of 1.5 µg/min calcitonin gene-related peptide and recorded migraine attacks including headache characteristics and associated symptoms. Information of familial...

  18. Randomised placebo-controlled trial on the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis

    OpenAIRE

    Tafazal, Suhayl I.; Ng, Leslie; Sell, Philip

    2006-01-01

    This is a double blind randomised controlled trial to assess the effectiveness of nasal salmon calcitonin in the treatment of lumbar spinal stenosis. The trial compared the outcome of salmon calcitonin nasal spray to placebo nasal spray in patients with MRI confirmed lumbar spinal stenosis. Lumbar spinal stenosis is one of the commonest conditions encountered by spine surgeons. It more frequently affects elderly patients and lumbar decompression has been used to treat the condition with varia...

  19. Cloning of two members of the calcitonin-family receptors from stingray, Dasyatis akajei: possible physiological roles of the calcitonin family in osmoregulation.

    Science.gov (United States)

    Suzuki, Nobuo; Sekiguchi, Toshio; Satake, Honoo; Kato, Kanoko; Nishiyama, Yudai; Takahashi, Hideya; Danks, Janine A; Martin, T John; Hattori, Atsuhiko; Nakano, Masaki; Kakikawa, Makiko; Yamada, Sotoshi; Ogoshi, Maho; Hyodo, Susumu; Yamaguchi, Yoko; Chowdhury, Vishwajit S; Hayakawa, Kazuichi; Funahashi, Hisayuki; Sakamoto, Tatsuya; Sasayama, Yuichi

    2012-05-15

    In cartilaginous fish, two cDNAs encoding calcitonin-family receptors were isolated for the first time from the stingray brain. The open reading frame of one receptor cDNA coded a 525-amino acid protein. The amino acid identity of this receptor to human calcitonin-receptor-like receptor (CRLR) is 64.5%, frog CRLR is 64.7%, and flounder CRLR is 61.2% and this was higher than to human calcitonin receptor (CTR) (46.1%), frog CTR (54.7%), and flounder CTR (48.9%). We strongly suggested that this receptor is a ray CRLR based on phylogenetic analysis. In case of the second receptor, amino acid identity among CRLRs (human 50.5%, frog 50.7%, flounder 48.0%) and CTRs (human 43.2%, frog 49.1%, flounder 41.8%) was similar. From phylogenetic analysis of both CRLRs and CTRs, we believe that this receptor is ray CTR. The expression of ray CRLR mRNA was predominantly detected in the nervous system (brain) and vascular system (atrium, ventricle, and gill), which reflects the similar localization of CGRP in the nervous and vascular systems as mammals. It was observed that the second receptor was expressed in several tissues, namely cartilage, brain, pituitary gland, gill, atrium, ventricle, pancreas, spleen, liver, gall bladder, intestine, rectal gland, kidney, testis and ovary. This localization pattern was very similar to flounder CTR. Both receptor mRNAs were strongly expressed in the gill. This suggests that the calcitonin-family members are involved in the osmoregulation of stingray as this fish is known to be euryhaline. When a stingray was transferred to diluted seawater (20% seawater), the expression of both receptors significantly decreased in the gill. Similar results were obtained in the kidney of the stingray. Thus, our cloning and isolation of both receptors in the stingray will be helpful for elucidation of their physiological role(s) such as osmoregulation including calcium metabolism of cartilaginous fish.

  20. Calcitonin Gene-Related Peptide (Cgrp, Adrenomedullin (Am, Amylin, And Calcitonin (Ct Receptors And Overlapping Biological Actions

    Directory of Open Access Journals (Sweden)

    J.A. Fischer

    2001-01-01

    Full Text Available CGRP, AM, amylin, and CT have in common N-terminal 6-7 amino acid ring structures linked by disulfide bridges and amidated C-termini required for biological activity. For the related bioactive peptides, receptor-binding sites linked to cAMP stimulation and to a lesser extent to the phospholipase C signaling pathway have been identified in tissue specific manner. The highest density of CGRP receptors has been recognized in the cerebellum and the spinal cord. There photoaffinity-labeled N-glycosylated 60,000 and 54,000 Mr proteins are converted to 46,000 and 41,000 Mr components following endoglycosidase F/N-glycosidase F treatment. The same proteins were specifically labeled with [125I]-hCGRP-I(1-37 and -(8-37. Some cross-reaction between the CGRP receptor and AM was evident whereas amylin and CT were only recognized at over 10-7 M. A different AM receptor localized predominantly in the lung recognized CGRP at low, and amylin and calcitonin at equally high concentrations. CT receptor binding sites have been identified in osteoclasts and in the periventricular region of the brain. They cross-reacted with amylin at low concentrations and with CGRP and AM at over 10-7 M. Amylin receptor binding sites cross-reacting with salmon CT and CGRP but not with hCT and adrenomedullin to any great extent were originally described by Sexton in the nucleus accumbens and may represent a second CGRP receptor. The structure of a CT receptor was elucidated by the group of Goldring in 1991 through molecular cloning, and of a 60% homologous human CT receptor-like receptor (CRLR shortly thereafter here. The latter was an orphan receptor until the discovery of the receptor-activity-modifying proteins (RAMP by Foord which upon coexpression yield a CGRP receptor with RAMP1 and an AM receptor with RAMP2. Coexpression of the hCT receptor isotype 2 revealed a CGRP/amylin receptor with RAMP1 and an amylin receptor isotype with RAMP3. The CRLR/RAMP1 receptor antagonized by

  1. Prevention and management of osteoporosis: consensus statements from the Scientific Advisory Board of the Osteoporosis Society of Canada. 9. Calcitonin in the treatment of osteoporosis.

    OpenAIRE

    Siminoski, K; Josse, R. G.

    1996-01-01

    OBJECTIVE: To describe potential therapeutic uses of calcitonin in the prevention and treatment of osteoporosis. OPTIONS: Parenterally and intranasally administered calcitonin (eel, salmon or human). OUTCOMES: Fracture, fracture pain and loss of bone mineral density in osteoporosis; increased bone mass, prevention of fractures, reduction of pain and improved quality of life associated with calcitonin treatment. EVIDENCE: Relevant clinical studies and reports were examined, with an emphasis on...

  2. The human airway epithelial basal cell transcriptome.

    Directory of Open Access Journals (Sweden)

    Neil R Hackett

    Full Text Available BACKGROUND: The human airway epithelium consists of 4 major cell types: ciliated, secretory, columnar and basal cells. During natural turnover and in response to injury, the airway basal cells function as stem/progenitor cells for the other airway cell types. The objective of this study is to better understand human airway epithelial basal cell biology by defining the gene expression signature of this cell population. METHODOLOGY/PRINCIPAL FINDINGS: Bronchial brushing was used to obtain airway epithelium from healthy nonsmokers. Microarrays were used to assess the transcriptome of basal cells purified from the airway epithelium in comparison to the transcriptome of the differentiated airway epithelium. This analysis identified the "human airway basal cell signature" as 1,161 unique genes with >5-fold higher expression level in basal cells compared to differentiated epithelium. The basal cell signature was suppressed when the basal cells differentiated into a ciliated airway epithelium in vitro. The basal cell signature displayed overlap with genes expressed in basal-like cells from other human tissues and with that of murine airway basal cells. Consistent with self-modulation as well as signaling to other airway cell types, the human airway basal cell signature was characterized by genes encoding extracellular matrix components, growth factors and growth factor receptors, including genes related to the EGF and VEGF pathways. Interestingly, while the basal cell signature overlaps that of basal-like cells of other organs, the human airway basal cell signature has features not previously associated with this cell type, including a unique pattern of genes encoding extracellular matrix components, G protein-coupled receptors, neuroactive ligands and receptors, and ion channels. CONCLUSION/SIGNIFICANCE: The human airway epithelial basal cell signature identified in the present study provides novel insights into the molecular phenotype and biology of

  3. The basal ganglia and apraxia.

    Science.gov (United States)

    Pramstaller, P P; Marsden, C D

    1996-02-01

    Ever since Liepmann's original descriptions at the beginning of the century apraxia has usually been attributed to damage confined to the cerebral cortex and/or cortico-cortical connecting pathways. However, there have been suggestions that apraxia can be due to deep subcortical lesions, which raises the question as to whether damage to the basal ganglia or thalamus can cause apraxia. We therefore analysed 82 cases of such 'deep' apraxias reported in the literature. These reports consisted of a small number (n=9) of cases studied neuropathologically, and a much larger group (n=73) in which CT or MRI was used to identify the size and extent of the lesion. The reports were subdivided into (i) those with small isolated lesions which involved nuclei of the basal ganglia or thalamus only, and not extending to involve periventricular or peristriatal white matter; (ii) those with large lesions which involved two or more of the nuclei, or one or more of these deep structures plus damage to closely adjacent areas including the internal capsule, periventricular or peristriatal white matter; and (iii) lesions sparing basal ganglia and thalamus but involving adjacent white matter. The main conclusions to be drawn from this meta-analysis are that lesions confined to the basal ganglia (putamen, caudate nucleus and globus pallidus) rarely, if ever, cause apraxia. Lesions affecting the lenticular nucleus or putamen nearly always intruded into the adjacent lateral white matter to involve association fibres, in particular those of the superior longitudinal fasciculus and frontostriatal connections. Apraxia occurred with deep lesions of the basal ganglia apparently sparing white matter in only eight out of the 82 cases. Apraxia was most commonly seen when there were lesions in the lenticular nucleus or putamen (58 out of 72 cases) with additional involvement of capsular, and particularly of periventricular or peristriatal, white matter. Lesions of the globus pallidus (no cases) or

  4. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis

    OpenAIRE

    Papadokostakis, G.; Damilakis, J; Mantzouranis, E.; Katonis, P.; Hadjipavlou, A.

    2005-01-01

    The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a nume...

  5. Calcitonin gene-related peptide does not cause migraine attacks in patients with familial hemiplegic migraine

    DEFF Research Database (Denmark)

    Hansen, Jakob M; Thomsen, Lise L; Olesen, Jes;

    2011-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP triggers migraine-like attacks in patients with migraine with aura and without aura. In contrast, patients with familial hemiplegic migraine (FHM) with known mutations did not report more migraine......-like attacks compared to controls. Whether CGRP triggers migraine-like attacks in FHM patients without known mutations is unknown....

  6. The control of calcium metabolism by parathyroid hormone, calcitonin and vitamin D

    Science.gov (United States)

    Potts, J. T., Jr.

    1976-01-01

    Advances in analysis of chemistry and physiology of parathyroid hormone, calcitonin, and Vitamin D are described along with development of techniques in radioassay methods. Emphasis is placed on assessment of normal and abnormal patterns of secretion of these hormones in specific relation to the physiological adaptations of weightlessness and space flight. Related diseases that involve perturbations in normal skeletal and calcium homeostasis are also considered.

  7. Comparison of Calcitonin and Pamidronate Treatments in Children with Osteogenesis Imperfecta

    Directory of Open Access Journals (Sweden)

    Neslihan Onenli Mungan

    2013-08-01

    Full Text Available Purpose: The main objective of this study was to compare the treatments of calcitonin and pamidronate by clinical, biochemical, and radiological findings in children with osteogenesis imperfecta and evaluate the efficiency of pamidronate treatment. Patients and methods: A total of 12 patients, aged 41±38 (1-120 months were studied. Group 1 was consisted of six patients who had received intranasal calcitonin at a dosage of 4-6 U/kg three times a week before switching to pamidronate treatment. Group 2 was also consisted of six patients who had received only pamidronate infusion at a dosage of 0.5-2 mg/kg every two months. Results: Annual fracture rates decreased from 2.72 ± 0.80 to 0.40 ± 0.70 (p0.05, and from -3.08 ± -0.61 to -2.29 ± -0.56 in pamidronate group. The difference between the Z-scores of bone mineral density after calcitonin and pamidronate treatments was statistically significant (p<0.05. The Z-scores of pre (-3.44 ± -0.96 and post (-2.47 ± -0.60 pamidronate treatments of whole 12 patients were significantly different (p<0.001. Conclusion: Pamidronate was significantly more effective in reducing pain, annual fracture rate, and increasing bone mineral density and mobility than calcitonin without any severe adverse effects even in the neonatal period and severe forms of osteogenesis imperfecta. [Cukurova Med J 2013; 38(4.000: 667-674

  8. N-trimethyl chitosan-modified liposomes as carriers for oral delivery of salmon calcitonin.

    Science.gov (United States)

    Huang, Aiwen; Makhlof, Abdallah; Ping, Qineng; Tozuka, Yuichi; Takeuchi, Hirofumi

    2011-11-01

    Therapeutic peptide and protein drugs have high specificity and activity in their functions but present challenges in their administration route, requiring development of new delivery systems to improve their bioavailability. The aim of this work was to investigate the role of N-trimethyl chitosan- (TMC-) coated liposomes in the oral administration of calcitonin. TMC with a degree of quaternization around 78% was synthesized and its mucoadhesive properties were examined in vitro using the mucin-particle method, which confirmed that TMC showed mucoadhesion comparable to that of chitosan. TMC-coated liposomes containing calcitonin were prepared and characterized as having a particle size of 262 nm, zeta potential of 35.8 mV and high entrapment efficiency (89.1%). The in vivo evaluation of mucoadhesion was carried out using confocal laser microscopy to observe the residence time and permeation extent after intragastric administration. The results showed that TMC-coated liposomes prolonged the residence time and increased the penetration effect of the liposomal system compared to non-coated liposomes. The study of pharmacological effects confirmed that TMC-coated liposomes increased the area above the blood calcium concentration-time curves (AAC) from 3.13 ± 20.50 to 448.84 ± 103.56 compared to the calcitonin solution. These results support the feasibility of TMC-coated liposomes as a new oral delivery system for peptide and protein drugs.

  9. Calcitonin receptor gene expression in K562 chronic myelogenous leukemic cells

    Directory of Open Access Journals (Sweden)

    Pondel Marc D

    2003-04-01

    Full Text Available Abstract Background The peptide hormone calcitonin (CT can significantly effect the proliferation rate of CT receptor (CTR positive human cancer cells. We wish to identify additional human cancers expressing CTRs and assay the effects of CT on their growth rates and signal transduction pathways. Results The expression of the human calcitonin receptor (hCTR gene in the chronic myelogenous leukemia cell line K562 was examined. RT-PCR on total RNA extracted from K562 cells detected the presence of hCTR mRNA. Further analysis demonstrated that multiple hCTR isoforms were present. Incubation of K562 cells with salmon calcitonin (sCT, but not amylin, caused an increase in intracellular levels of cAMP similar to that induced by forskolin treatment. We further demonstrated that butyrate induced erythroid differentiation of K562 cells caused a significant decrease in hCTR mRNA levels. However, phorbol myristate acetate (PMA induced megakaryocytic differentiation of these cells had no significant effect on hCTR mRNA levels. We demonstrated that exposure to various concentrations of sCT had no effect on the cellular proliferation of K562 cells in vitro. Conclusion Chronic myelogenous k562 cells express multiple CTR isoforms. However, CT does not effect K562 proliferation rates. It is likely that the small increase in intracellular levels of cAMP following CT treatment is not sufficient to interfere with cellular growth.

  10. The effectiveness of calcitonin on chronic back pain and daily activities in postmenopausal women with osteoporosis.

    Science.gov (United States)

    Papadokostakis, G; Damilakis, J; Mantzouranis, E; Katonis, P; Hadjipavlou, A

    2006-03-01

    The aim of this study was to investigate the effect of nasal calcitonin on chronic back pain and disability attributed to osteoporosis. The study design involved three groups of osteoporotic postmenopausal women suffering from chronic back pain. Group I consisted of 40 women with vertebral fractures, group II of 30 women with degenerative disorders and group III of 40 patients with non specific chronic back pain and without abnormality on plain X-rays. Pain intensity was measured using a numerical rating scale (NRS) and disability due to back pain was measured using the Oswestry disability questionnaire. The patients were randomly assigned to receive, for three months, either 200 IU intranasal salmon calcitonin and 1,000 mg of oral calcium daily (groups IA, IIA, IIIA) or 1,000 mg of oral calcium daily (groups IB, IIB, IIIB). Repeated measures ANOVA showed that there were no significant time, group or interaction effects for pain intensity and disability in any of the groups studied. Mean Oswestry and NRS scores were reduced during the follow-up period in the groups IA, IIIA, but the differences between the two time points were not statistically significant. Intranasal calcitonin has no effect on chronic back pain intensity and functional capacity of osteoporotic women regardless of the presence of fractures, degenerative disorders or chronic back pain of non-specific etiology.

  11. Effect of salmon calcitonin on osteoporosis and level of bone metabolism markers

    Institute of Scientific and Technical Information of China (English)

    Xian-Feng Fan; Xing-Hua Huang; Yun-Yong Huang; Ming-Jian Hu

    2015-01-01

    Objective:To study the effect of osteoporosis calcitonin salmon on the level of bone metabolism markers in patients with osteoporosis.Methods: A total of 140 cases with osteoporosis were randomly divided into control group and observation group, with 70 cases in each. Patients in control group were treated with calcitriol soft capsules and chewable calcium vitamin D. Patients in observation group were treated with salmon calcitonin.Results:The total efficiency of the observation group patients was 85.71%, significantly higher than 70.00% that of control group (P<0.05). After treatment, BMD of Torch, Neck, L1-L4 and Ward's area in observation group patients were significantly higher than that of control group (P<0.01). After treatment, bone metabolism related indicatorsβ-CTX, N-MID, ALP level in observation group patients were significantly lower than that of control group, and hCT level in observation group patients was significantly higher than that of control group (P<0.01). Conclusions:Salmon calcitonin is effective in treatment of osteoporosis. It can effectively relieve the symptoms, increase bone density and improve bone metabolism.

  12. Migraine attacks the Basal Ganglia

    Directory of Open Access Journals (Sweden)

    Bigal Marcelo

    2011-09-01

    Full Text Available Abstract Background With time, episodes of migraine headache afflict patients with increased frequency, longer duration and more intense pain. While episodic migraine may be defined as 1-14 attacks per month, there are no clear-cut phases defined, and those patients with low frequency may progress to high frequency episodic migraine and the latter may progress into chronic daily headache (> 15 attacks per month. The pathophysiology of this progression is completely unknown. Attempting to unravel this phenomenon, we used high field (human brain imaging to compare functional responses, functional connectivity and brain morphology in patients whose migraine episodes did not progress (LF to a matched (gender, age, age of onset and type of medication group of patients whose migraine episodes progressed (HF. Results In comparison to LF patients, responses to pain in HF patients were significantly lower in the caudate, putamen and pallidum. Paradoxically, associated with these lower responses in HF patients, gray matter volume of the right and left caudate nuclei were significantly larger than in the LF patients. Functional connectivity analysis revealed additional differences between the two groups in regard to response to pain. Conclusions Supported by current understanding of basal ganglia role in pain processing, the findings suggest a significant role of the basal ganglia in the pathophysiology of the episodic migraine.

  13. Intrathecal Amylin and Salmon Calcitonin Affect Formalin Induced c-Fos Expression in the Spinal Cord of Rats

    Directory of Open Access Journals (Sweden)

    Zahra Khoshdel

    2014-11-01

    Full Text Available Background:Amylin and Salmon Calcitonin belong to the calcitonin family of peptides and have high affinity binding sites in the rat spinal cord. The aim of this study was to characterize receptors for Amylin and Salmon Calcitonin functionally in the spinal cord of rats. We assessed the expression of c-Fos in response to intraplantar formalin in the lumbar regions of the spinal cord in conscious rats. Methods:Amylin (0.05 nmoles or Salmon Calcitonin (0.005 nmoles was administered intrathecally (i.t. 10 minutes before the start of the formalin test. Antagonists were injected intrathecally 10 minutes before the administration of either of the peptides. Results: Two hours after formalin stimulation, rats pretreated intrathecally by either Amylin or Salmon Calcitonin, showed lower numbers of c-Fos immunoreactive nuclei in their lumbar spinal cord as compared to rats pretreated with saline. These effects were reversed upon co-administration of either of the Amylin antagonists AC187 or rat amylin8-37, but not rat α-CGRP8-37. A few cells with c-Fos immunoreactivity were found in the lumbar spinal cord of rats two hours after i.t. injection of saline, Amylin and/or Salmon Calcitonin. However, Fos-like immunoreactivity was increased in the lumbar spinal cord two hours after i.t. treatment of either of the antagonists AC187 and rat amylin8-37,when compared to saline treated rats. Conclusion:Both Amylin and Salmon Calcitonin inhibit formalin induced c-Fos expression in the rat lumbar spinal cord when administered intrathecally. Effects of the two peptides were possibly produced by undefined receptors.

  14. Heat hyperalgesia and mechanical hypersensitivity induced by calcitonin gene-related peptide in a mouse model of neurofibromatosis.

    Directory of Open Access Journals (Sweden)

    Stephanie White

    Full Text Available This study examined whether mice with a deficiency of neurofibromin, a Ras GTPase activating protein, exhibit a nociceptive phenotype and probed a possible contribution by calcitonin gene-related peptide. In the absence of inflammation, Nf1+/- mice (B6.129S6 Nf1/J and wild type littermates responded comparably to heat or mechanical stimuli, except for a subtle enhanced mechanical sensitivity in female Nf1+/- mice. Nociceptive phenotype was also examined after inflammation induced by capsaicin and formalin, which release endogenous calcitonin gene-related peptide. Intraplantar injection of capsaicin evoked comparable heat hyperalgesia and mechanical hypersensitivity in Nf1+/- and wild type mice of both genders. Formalin injection caused a similar duration of licking in male Nf1+/- and wild type mice. Female Nf1+/- mice licked less than wild type mice, but displayed other nociceptive behaviors. In contrast, intraplantar injection of CGRP caused greater heat hyperalgesia in Nf1+/- mice of both genders compared to wild type mice. Male Nf1+/- mice also exhibited greater mechanical hypersensitivity; however, female Nf1+/- mice exhibited less mechanical hypersensitivity than their wild type littermates. Transcripts for calcitonin gene-related peptide were similar in the dorsal root ganglia of both genotypes and genders. Transcripts for receptor activity-modifying protein-1, which is rate-limiting for the calcitonin gene-related peptide receptor, in the spinal cord were comparable for both genotypes and genders. The increased responsiveness to intraplantar calcitonin gene-related peptide suggests that the peripheral actions of calcitonin gene-related peptide are enhanced as a result of the neurofibromin deficit. The analgesic efficacy of calcitonin gene-related peptide receptor antagonists may therefore merit investigation in neurofibromatosis patients.

  15. Effects of Nasal Calcitonin vs. Oral Gabapentin on Pain and Symptoms of Lumbar Spinal Stenosis: A Clinical Trial Study.

    Science.gov (United States)

    Haddadi, Kaveh; Asadian, Leila; Isazade, Ahdie

    2016-01-01

    Lumbar spinal stenosis (LSS) is a chronic and prevalent disease that occurs in 10.8% of the general population, mostly in old age. We designed the first clinical trial study to compare the effects of administering the nasal salmon calcitonin spray and gabapentin in patients with LSS. In this clinical trial, 90 patients with symptoms of neurogenic claudication and magnetic resonance imaging-proven LSS were randomly assigned to nasal salmon calcitonin, gabapentin, or placebo treatments for eight weeks (30 participants in each group). This was followed by a washout period of four weeks. After three months of study and after four weeks off the prescription, mean values of Oswestry Disability Index in the calcitonin, gabapentin, and control groups were 23 ± 12.05, 32 ± 16.08, and 38 ± 22.09, respectively (P ≤ 0.05, calcitonin group vs. gabapentin group, and P ≤ 0. 001, calcitonin group vs. control group with respect to pretreatment scores). Thus, three months after the treatment, although most of the patients in the control group had a satisfactory period of improvement, the improvement in the calcitonin group was more than the other two groups with a significant difference (P ≤ 0.05 when compared to gabapentin group and P ≤ 0.01 when compared to placebo group). We revealed that the 200 International Unit (IU) and nasal calcitonin spray daily are more effective compared to 300 mg gabapentin three times per day and the placebo effect for eight weeks of treatment of symptoms of patients with LSS.

  16. 降钙素原在全身炎症反应综合征中的临床价值%Calcitonin original clinical value in systemic inflammatory response syndrome

    Institute of Scientific and Technical Information of China (English)

    张志强

    2015-01-01

    Objective To explore the serum calcitonin original value in the diagnosis of systemic inflammatory response syndrome.Methods Select 120 cases of patients with systemic inflammatory response syndrome as the research object, the bacteria infection in 77 cases (group A), the bacterial infection 43 cases (group B), test and compare the two groups of patients the WBC (white blood cell count), hs - CRP (hypersensitive c-reactive protein), PCT (calcitonin former) level.Results A group of patients with PCT were significantly higher than that of group B, statistically significant difference (P 0.05);A组患者的PCT水平显著高于B组,P<0.05,差异具有统计学意义(P<0.05)。患者危重评分与PCT水平呈负相关(r=-0.798,P<0.05)。结论:在全身炎症反应综合征的病原学诊断中,PCT的诊断价值优于中心粒细胞占比、WBC、hs-CRP,是敏感性较高的一种血清学标志,具有重要的临床应用价值。

  17. Molecular design and prediction of bioactivity of chimeric calcitonin%嵌合降钙素的分子设计与生物学活性预测

    Institute of Scientific and Technical Information of China (English)

    王玉梅; 周一江; 张学成

    2009-01-01

    Objective:To design one new type of calcitonin(CT)analogue with higher bioactivity but lower sideeffects.Methods:According to the principle of bioactive peptide drug design and previous work experience,an assumption was raised that bioactivity of new type of calcitonin call be improved by increasing isoelectric point(pI),N-terminal hydrophobicity and C-terminal hydrophilicity of calcitonin molecules.Based on human and salmon calcitonin,a large number of calcitonin analogues were designed and then analyzed in sequence with the help of protein analysis software.The contradictions between activities and side-effects were taken into account and a new type of calcitonin analogue to meet the requirements was determined.Results:Calcitonin analogue meeting bioactivity requirements was chimeric calcitonin of human and salmon calcitonin.Structure prediction showed that the molecular conflonnation of new calcitonin analogue was similar to salmon calcitonin(sCT).The isoelectric point of chimeric calcitonin analogue was between human and salmon calcitonin.The N-terminal hydrophobicity of new calcitonin analogue Was increased more than that of human calcitonin(hCT)and as same as that of salmon calcitonin.Its C-terminal hydrophilicity was as same as that of salmon calcitonin and increased with a high degree compared with human calcitonin.Conclusion:The activity of new calcitonin analogue was predicted to have higher bioactivity than that of human calcitonin,while the side-effects was lower than that of salmon calcitonin.%目的:设计一种高活性、低副作用的降钙素类似物.方法:根据生物活件肽药物设计原理,结合前人的工作经验,提出提高降钙素分子等电点(pI)、增加N-末端疏水性和C-末端亲水性可以提高新型降钙素活件的假设.以人和鲑鱼降钙素为先导物,设计了大量的降钙素类似物,然后利用蛋白质分析计算软件,逐一分析,综合考虑到副作用与活性的矛盾,确定符合要求的新型

  18. Cellular uptake but low permeation of human calcitonin-derived cell penetrating peptides and Tat(47-57) through well-differentiated epithelial models

    DEFF Research Database (Denmark)

    Tréhin, Rachel; Krauss, Ulrike; Beck-Sickinger, Annette G;

    2004-01-01

    To investigate whether cell penetrating peptides (CPP) derived from human calcitonin (hCT) possess, in addition to cellular uptake, the capacity to deliver their cargo through epithelial barriers.......To investigate whether cell penetrating peptides (CPP) derived from human calcitonin (hCT) possess, in addition to cellular uptake, the capacity to deliver their cargo through epithelial barriers....

  19. The Basal Ganglia and Motor Control

    OpenAIRE

    Groenewegen, Henk J.

    2003-01-01

    This paper briefly reviews the functional anatomy of the basal ganglia and their relationships with the thalamocortical system. The basal ganglia, including the striatum, pallidum, subthalamic nucleus, and substantia nigra, are involved in a number of parallel, functionally segregated cortical-subcortical circuits. These circuits support a wide range of sensorimotor, cognitive and emotional-motivational brain functions. A main role of the basal ganglia is the learning and selection of the mos...

  20. Functional Neuroanatomy of the Basal Ganglia

    OpenAIRE

    Lanciego, José L.; Luquin, Natasha; Obeso, José A.

    2012-01-01

    The “basal ganglia” refers to a group of subcortical nuclei responsible primarily for motor control, as well as other roles such as motor learning, executive functions and behaviors, and emotions. Proposed more than two decades ago, the classical basal ganglia model shows how information flows through the basal ganglia back to the cortex through two pathways with opposing effects for the proper execution of movement. Although much of the model has remained, the model has been modified and amp...

  1. A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats

    DEFF Research Database (Denmark)

    Andreassen, Kim V; Feigh, Michael; Hjuler, Sara T

    2014-01-01

    obese (DIO) and Zucker diabetic fatty (ZDF) rats. In vitro, KBP-042 demonstrated superior binding affinity and activation of amylin and calcitonin receptors, and ex vivo, KBP-042 exerted inhibitory action on stimulated insulin and glucagon release from isolated islets. In vivo, KBP-042 induced...... a superior and pronounced reduction in food intake in conjunction with a sustained pair-fed corrected weight loss in DIO rats. Concomitantly, KBP-042 improved glucose homeostasis and reduced hyperinsulinemia and hyperleptinemia in conjunction with enhanced insulin sensitivity. In ZDF rats, KBP-042 induced......The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced...

  2. Substance P and calcitonin gene-related peptide expression in dorsal root ganglia in sciatic nerve injury rats

    Institute of Scientific and Technical Information of China (English)

    Changma Fu; Zongsheng Yin; Defu Yu; Zuhua Yang

    2013-01-01

    The neuropeptides, substance P and calcitonin gene-related peptide, have been shown to be involved in pain transmission and repair of sciatic nerve injury. A model of sciatic nerve defect was prepared by dissecting the sciatic nerve at the middle, left femur in female Sprague Dawley rats. The two ends of the nerve were encased in a silica gel tube. L5 dorsal root ganglia were harvested 7, 14 and 28 days post sciatic nerve injury for immunohistochemical staining. Results showed that substance P and cal-citonin gene-related peptide expression increased significantly in dorsal root ganglion of rats with sci-atic nerve injury. This increase peaked at 7 days, declined at 14 days, and reduced to normal levels by 28 days post injury. The findings indicate that the neuropeptides, substance P and calcitonin gene-related peptide, mainly increased in the early stages after sciatic nerve injury.

  3. The effect of calcitonin on beta-endorphin levels in postmenopausal osteoporotic patients with back pain.

    Science.gov (United States)

    Ofluoglu, D; Akyuz, G; Unay, O; Kayhan, O

    2007-01-01

    The purpose of this study was to evaluate the efficacy of calcitonin on beta-endorphin levels in female patients experiencing back pain associated with postmenopausal osteoporosis. The secondary purpose was to assess the pain and quality of life in these patients. There were 30 patients with a mean age of 58.2+/-5.4 years in the treatment group and 26 patients with a mean age of 58.8+/-5.2 years in the placebo group in this randomized, placebo-controlled study. The patients subcutaneously received 100 IU salmon calcitonin or placebo injections and 1,000 mg elementary calcium for 2 weeks. Baseline plasma beta-endorphin levels were measured and repeated after 2 weeks. Patients' pain and quality of life (QOL) were evaluated by using the Visual Analogue Scale, Modified Face Scale, Beck Depression Index, and Nottingham Health Profile. Patients' global assessment of disease activity was also performed at baseline and at the end of the first and second week. We found that plasma beta-endorphin levels in the treatment group were significantly higher than the placebo group at the end of the second week (p<0.001). Although pain and QOL scores were improved at the end of the second week in both groups (p<0.05), the improvement in the treatment group was more significant when compared with the placebo group (p<0.05). Therefore, calcitonin is an analgesic agent, as it increases the plasma beta-endorphin levels in patients with postmenopausal osteoporosis, which consequently improves QOL.

  4. The role of calcitonin gene–related peptide in peripheral and central pain mechanisms including migraine

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H.; Johnson, Kirk W.

    2017-01-01

    Abstract Calcitonin gene–related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene–related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene–related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine. PMID:28301400

  5. Treatment of aneurysmal bone cysts by percutaneous CT-guided injection of calcitonin and steroid

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Connie Y.; Kattapuram, Susan V.; Huang, Ambrose J.; Simeone, F.J.; Torriani, Martin; Bredella, Miriam A. [Massachusetts General Hospital, Department of Radiology Division of Musculoskeletal Imaging and Intervention, Boston, MA (United States)

    2017-01-15

    To determine the efficacy and safety of percutaneous calcitonin and steroid injection in the treatment of aneurysmal bone cysts (ABCs). Our study was IRB-approved and HIPAA-compliant. We reviewed pre- and post-procedural imaging studies and medical records of all CT-guided percutaneous injections of ABCs with calcitonin and steroid performed at our institution between 2003 and 2015. Treatment success based on imaging was categorized as substantial (51-100 %), partial (1-50 %), or none (0 %) by comparing radiographs of the lesion before and after treatment. Our study group comprised 9 patients (7 female, 2 male; mean age 19 ± 5 (range 12-25) years). ABCs were located in the pubis (n = 3), femur (n = 2), and humerus/scapula/ilium/sacrum (n = 1 for each). One patient did not have any clinical or imaging follow-up. For the other 8 patients, clinical and imaging follow-up ranged from 1 to 93 months (mean 16 ± 29 months). One patient had two injections, and 1 patient had three injections. Six out of eight patients (75 %) had complete symptomatic relief and 2 patients (25 %) had partial symptomatic relief after initial injection. Imaging follow-up revealed substantial imaging response in 4 out of 8 patients (50 %). There was a partial imaging response in 2 patients (25 %) and no imaging response in 2 out of 8 patients (25 %), and all 4 of these patients had local recurrence. There were no complications. Percutaneous CT-guided injection of ABCs with calcitonin and steroid is a safe and effective treatment. Lack of imaging response may necessitate more aggressive treatment to minimize local recurrence. (orig.)

  6. The role of calcitonin gene-related peptide in peripheral and central pain mechanisms including migraine.

    Science.gov (United States)

    Iyengar, Smriti; Ossipov, Michael H; Johnson, Kirk W

    2017-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide found primarily in the C and Aδ sensory fibers arising from the dorsal root and trigeminal ganglia, as well as the central nervous system. Calcitonin gene-related peptide was found to play important roles in cardiovascular, digestive, and sensory functions. Although the vasodilatory properties of CGRP are well documented, its somatosensory function regarding modulation of neuronal sensitization and of enhanced pain has received considerable attention recently. Growing evidence indicates that CGRP plays a key role in the development of peripheral sensitization and the associated enhanced pain. Calcitonin gene-related peptide is implicated in the development of neurogenic inflammation and it is upregulated in conditions of inflammatory and neuropathic pain. It is most likely that CGRP facilitates nociceptive transmission and contributes to the development and maintenance of a sensitized, hyperresponsive state not only of the primary afferent sensory neurons but also of the second-order pain transmission neurons within the central nervous system, thus contributing to central sensitization as well. The maintenance of a sensitized neuronal condition is believed to be an important factor underlying migraine. Recent successful clinical studies have shown that blocking the function of CGRP can alleviate migraine. However, the mechanisms through which CGRP may contribute to migraine are still not fully understood. We reviewed the role of CGRP in primary afferents, the dorsal root ganglion, and in the trigeminal system as well as its role in peripheral and central sensitization and its potential contribution to pain processing and to migraine.

  7. Serum sickness

    Science.gov (United States)

    ... the problem should be stopped. Avoid using that medicine or antiserum in the future. ... Call your provider if you received medicine or antiserum in the last 4 weeks and have symptoms of serum sickness.

  8. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...... releases CGRP, and the release is regulated by Ca2+ ions and voltage-gated calcium channels.......Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons...

  9. Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura

    DEFF Research Database (Denmark)

    Hansen, Jakob Møller; Hauge, Anne Werner; Olesen, J.

    2010-01-01

    Calcitonin gene-related peptide (CGRP) is a key molecule in migraine pathogenesis. Intravenous CGRP infusion triggers delayed migraine-like attacks in patients with migraine without aura (MO). In contrast to patients with MO, in prior studies patients with familial hemiplegic migraine (FHM) did...... not report more migraine-like attacks compared to controls. Whether CGRP triggers migraine in patients with typical (non-hemiplegic) migraine with aura is (MA) unknown. In the present study we examined the migraine inducing effect of CGRP infusion in patients suffering from MA and healthy controls....

  10. Calcitonin gene-related peptide targeted immunotherapy for migraine: progress and challenges in treating headache.

    Science.gov (United States)

    Peroutka, Stephen J

    2014-06-01

    A role for calcitonin gene-related peptide (CGRP) in the pathophysiology of migraine has been established over the past 25 years. There have now been at least five different small-molecule CGRP antagonists that have demonstrated statistical proof of efficacy in the acute treatment of migraine. At present, multiple clinical trials are underway that are assessing the ability of long-acting antibodies against CGRP to prevent frequent migraine attacks. This review summarizes the existing data concerning the role of CGRP in migraine and attempts to highlight some possible outcomes from the ongoing anti-CGRP antibody trials.

  11. Early recognition of basal cell naevus syndrome

    NARCIS (Netherlands)

    Veenstra-Knol, HE; Scheewe, JH; van der Vlist, GJ; van Doorn, ME; Ausems, MGEM

    2005-01-01

    The basal cell naevus syndrome is an autosomal dominant syndrome characterised by major manifestations such as basal cell carcinomas, jaw cysts, palmar or plantar pits, and intracranial calcifications. Early recognition is important in order to reduce morbidity due to cutaneous and cerebral malignan

  12. Modeling Serum Creatinine in Septic ICU Patients

    DEFF Research Database (Denmark)

    De Gaetano, Andrea; Cortese, Giuliana; Pedersen, Morten Gram

    2004-01-01

    Serum creatinine is a metabolite assumed to be constantly produced by the normally functioning muscle mass and is a good measure for monitoring daily renal function in the intensive care unit (ICU). High serum creatinine levels or an abnormal departure from normal pre-disease basal levels....... The present work details the structure of a model describing observed creatinine serum concentration (CSC) variations, depending on the time-varying septic insult to renal function in ICU patients, as well as the estimation of its parameters. CSC determinations were routinely obtained from 12 patients...

  13. Nevoid Basal Cell Carcinoma Syndrome (Gorlin Syndrome).

    Science.gov (United States)

    Bresler, Scott C; Padwa, Bonnie L; Granter, Scott R

    2016-06-01

    Nevoid basal cell carcinoma syndrome, or basal cell nevus syndrome (Gorlin syndrome), is a rare autosomal dominantly inherited disorder that is characterized by development of basal cell carcinomas from a young age. Other distinguishing clinical features are seen in a majority of patients, and include keratocystic odontogenic tumors (formerly odontogenic keratocysts) as well as dyskeratotic palmar and plantar pitting. A range of skeletal and other developmental abnormalities are also often seen. The disorder is caused by defects in hedgehog signaling which result in constitutive pathway activity and tumor cell proliferation. As sporadic basal cell carcinomas also commonly harbor hedgehog pathway aberrations, therapeutic agents targeting key signaling constituents have been developed and tested against advanced sporadically occurring tumors or syndromic disease, leading in 2013 to FDA approval of the first hedgehog pathway-targeted small molecule, vismodegib. The elucidation of the molecular pathogenesis of nevoid basal cell carcinoma syndrome has resulted in further understanding of the most common human malignancy.

  14. Avaliação dos níveis basais de FSH em pacientes inférteis com endometriose profunda de ovário tratadas cirurgicamente Evaluation of basal FSH serum levels in infertile patients with deep ovarian endometriosis who underwent surgery

    Directory of Open Access Journals (Sweden)

    Sandra Frankfurt

    2009-07-01

    Full Text Available OBJETIVO: avaliar a reserva ovariana de pacientes inférteis portadoras de endometriose profunda de ovário, submetidas à cirurgia excisional dos endometriomas, atendidas entre os meses de Fevereiro e Novembro de 2008. MÉTODOS: estudo prospectivo que incluiu 30 pacientes portadoras de endometriose graus III e IV com comprometimento profundo de ovário submetidas à cirurgia excisional dos endometriomas e 30 pacientes portadoras de endometriose graus I e II que foram alocadas como Grupo Controle. A reserva ovariana foi avaliada indiretamente a partir do valor do hormônio folículo estimulante (FSH basal (U/L, entre o terceiro e quinto dias do ciclo, após um período de 12 meses da cirurgia. O índice de massa corpórea (IMC foi calculado conforme a fórmula de Quetelet [peso (kg/estatura (cm²]. Para a comparação das variáveis "idade", "IMC" e "valores de FSH basal" entre os grupos, foi utilizado o teste não paramétrico U de Mann-Whitney. RESULTADOS: não foi encontrada diferença significativa entre os grupos em relação à idade e ao IMC. Em relação ao FSH basal, observou-se que, no grupo das pacientes com endometriose profunda, o valor médio foi de 7,0 U/L, enquanto que, no Grupo Controle, foi de 5,6 U/L (p=0,3, o que demonstra que a diferença no valor médio de FSH encontrado nos dois grupos não foi significativa. CONCLUSÕES: a cirurgia não influenciou de forma deletéria a reserva ovariana das pacientes com endometriose profunda de ovário.PURPOSE: to evaluate the ovarian reserve of infertile patients with severe ovarian endrometriosis, submitted to excisional surgery of endometriomas and attended from February to November, 2008. METHODS: prospective study, including 30 patients with endometriosis grades III and IV, with severe ovarian impairment, submitted to excisional surgery of the endometriomas, and 30 patients with endometriosis grades I and II, allocated as a Control Group. The ovarian reserve was indirectly assessed

  15. Salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis.

    Science.gov (United States)

    Dexue, Liu; Yueyue, Zheng

    2014-11-01

    To explore the reasonable treatment scheme of salmon calciteonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis, patients were randomly divided into Group A, B and C, and they were given the salmon calcitonin every time 50 IU, subcutaneous injection. The Group A were 1 time a day, for 15 days; Group B were 1 time every 2 days, for 30 days; Group C, one time three days for 90 days. Then to observe the symptoms have efficiency, bone density T value change, incidence rate, incidence of side effects and treatment of loss rate of fracture. Efficiency of symptoms: Group A is lower and there is no difference in Group B and C. T Degree: Group C was significantly increased and Group A was the lowest. Fracture incidence of Group B and C were significantly lower than Group A, and there is no difference in Group B and C. Turnover rate: Group A was significantly lower than B and C, and there is no difference in Group B and C. There is low incidence of side effects in the three groups and they three have no significant difference. It is effective and safe to use salmon calcitonin in the treatment of elderly women with type 2 diabetes complicated with osteoporosis. 50 IU each time, subcutaneous injection, 1 time every 3 days, for 3 months is a reasonable solution.

  16. Long-term treatment of osteogenesis imperfects tarda in adults with salmon calcitonin and calcium

    Energy Technology Data Exchange (ETDEWEB)

    Zanzi, I.; Wallach, S.; Ellis, K.J.; Aloia, J.F.; Atkins, H.L.; Cohn, S.H.

    1976-02-01

    Three postmenopausal women with osteogenesis imperfecta (O.I.) tarda were treated with daily salmon calcitonin (sCT) and calcium supplements for 12 to 33 months. Total body calcium (TBCa) measured by total body neutron activation analysis revealed a marked deficit exceeding that of severely osteoporotic women. In one patient a rapid loss of TBCa of 5 percent at five months of treatment was partially reversed after twelve months of treatment. In eight subsequent months of Ca supplementation alone, the loss of TBCa resumed and amounted to 11 percent. The second patient increased TBCa by 9 percent after a total of 33 months of sCT and Ca supplementation. The third patient also showed a rapid decrease in TBCa of 8 percent during one year of sCT and Ca, but she was also receiving systemic corticosteroids for asthma. Her TBCa recovered to 8 percent above baseline eight months after stopping sCT, continuation of the Ca and a drastic decrease in the dose of corticosteroids. The action of sCT in this patient might have been impaired by the concomitant administration of corticosteroids. Urinary hydroxyproline decreased from initial normal values in two patients suggesting continued inhibition of bone resorption. The results confirm previous work using calcitonin in children with O.I. and suggest that sCT may also be of benefit in adults with O.I. (auth)

  17. Metastatic Basal Cell Carcinoma Accompanying Gorlin Syndrome

    Directory of Open Access Journals (Sweden)

    Yeliz Bilir

    2014-01-01

    Full Text Available Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts, the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  18. Metastatic Basal cell carcinoma accompanying gorlin syndrome.

    Science.gov (United States)

    Bilir, Yeliz; Gokce, Erkan; Ozturk, Banu; Deresoy, Faik Alev; Yuksekkaya, Ruken; Yaman, Emel

    2014-01-01

    Gorlin-Goltz syndrome or basal cell nevus syndrome is an autosomal dominant syndrome characterized by skeletal anomalies, numerous cysts observed in the jaw, and multiple basal cell carcinoma of the skin, which may be accompanied by falx cerebri calcification. Basal cell carcinoma is the most commonly skin tumor with slow clinical course and low metastatic potential. Its concomitance with Gorlin syndrome, resulting from a mutation in a tumor suppressor gene, may substantially change morbidity and mortality. A 66-year-old male patient with a history of recurrent basal cell carcinoma was presented with exophthalmus in the left eye and the lesions localized in the left lateral orbita and left zygomatic area. His physical examination revealed hearing loss, gapped teeth, highly arched palate, and frontal prominence. Left orbital mass, cystic masses at frontal and ethmoidal sinuses, and multiple pulmonary nodules were detected at CT scans. Basal cell carcinoma was diagnosed from biopsy of ethmoid sinus. Based on the clinical and typical radiological characteristics (falx cerebri calcification, bifid costa, and odontogenic cysts), the patient was diagnosed with metastatic skin basal cell carcinoma accompanied by Gorlin syndrome. Our case is a basal cell carcinoma with aggressive course accompanying a rarely seen syndrome.

  19. Analgesic effect of salmon calcitonin in osteoporotic vertebral fractures: a double-blind placebo-controlled clinical study.

    Science.gov (United States)

    Lyritis, G P; Tsakalakos, N; Magiasis, B; Karachalios, T; Yiatzides, A; Tsekoura, M

    1991-12-01

    Back pain due to vertebral collapse is the main symptom of postmenopausal osteoporosis. The clinical picture in these crush fractures varies, depending on the type and the location of fracture, but in general, a new vertebral crush fracture gives rise to severe pain that immobilizes the patient and necessitates bedrest. In this double-blind controlled clinical trial, 56 patients who had recently (within the last 3 days) suffered an osteoporotic vertebral fracture were hospitalized for a period of 14 days. Salmon calcitonin (100 IU) or placebo injections were given daily. Pain was rated daily on a 10-point scale by the same observers. Blood and urinary parameters were also evaluated. The results showed a significant (P less than 0.001) difference in pain intensity between the calcitonin group and the placebo group. This beneficial effect was generally apparent from the second day of treatment onward, and over the following 2 weeks, the patients were able to sit and stand, and gradually started to walk again. A significant decrease in urinary hydroxyproline and urinary calcium was also noted in the calcitonin group. It is concluded that calcitonin exerts a beneficial effect on back pain following a vertebral crush fracture.

  20. Forearm vascular response to nitric oxide and calcitonin gene-related peptide: comparison between migraine patients and control subjects.

    NARCIS (Netherlands)

    Hoon, J.N. de; Smits, P.; Troost, J.; Struijker-Boudier, H.A.; Bortel, L.M. van

    2006-01-01

    The forearm vascular response to nitric oxide (NO) and calcitonin gene-related peptide (CGRP) was investigated in 10 migraine patients and 10 matched control subjects. Changes in forearm blood flow (FBF) during intrabrachial infusion of: (i) serotonin (releasing endogenous NO), (ii) sodium nitroprus

  1. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers

    DEFF Research Database (Denmark)

    Kruuse, C; Iversen, Helle Klingenberg; Jansen-Olesen, I

    2010-01-01

    calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers...

  2. Role for voltage gated calcium channels in calcitonin gene-related peptide release in the rat trigeminovascular system

    DEFF Research Database (Denmark)

    Amrutkar, D V; Ploug, K B; Olesen, J;

    2011-01-01

    Clinical and genetic studies have suggested a role for voltage gated calcium channels (VGCCs) in the pathogenesis of migraine. Release of calcitonin gene-related peptide (CGRP) from trigeminal neurons has also been implicated in migraine. The VGCCs are located presynaptically on neurons and are i...

  3. Parathyroid hormone, calcitonin, and vitamin D 1974: Present status of physiological studies and analysis of calcium homeostasis

    Science.gov (United States)

    Potts, J. T., Jr.; Swenson, K. G.

    1975-01-01

    The role of parathyroid hormone, calcitonin, and vitamin D in the control of calcium and bone metabolism was studied. Particular emphasis was placed on the physiological adaptation to weightlessness and, as a potential model for this purpose, on the immobilization characteristic of space flight or prolonged bed rest. The biosynthesis, control of secretion, and metabolism of these hormonal agents is considered.

  4. Dilatory responses to acetylcholine, calcitonin gene-related peptide and substance P in the congestive heart failure rat

    DEFF Research Database (Denmark)

    Bergdahl, A; Valdemarsson, S; Nilsson, T;

    1999-01-01

    It was examined to what extent congestive heart failure (CHF) in rats, induced by ligation of the left coronary artery, affects the vascular responses to the vasodilatory substances acetylcholine (ACh), calcitonin gene-related peptide (CGRP), and substance P (SP). After induction of CHF status...

  5. A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats

    DEFF Research Database (Denmark)

    Feigh, M; Henriksen, K; Andreassen, K V

    2011-01-01

    To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes....

  6. Thermodynamic Significance of Human Basal Metabolism

    Institute of Scientific and Technical Information of China (English)

    WangCuncheng

    1993-01-01

    The human basal state,a non-equilibrium steady state,is analysed in this paper in the light of the First and Second Laws of Thermodynamics whereby the thermodynamic significance of the basal metabolic rate and its distinction to the dissipation function and exergy loss are identified.The analysis demonstrates the correct expression of the effects of the blood flow on the heat balance in a human-body bio-heat model and the relationship between the basal metabolic rate and the blood perfusion.

  7. Neglected giant scalp Basal cell carcinoma

    DEFF Research Database (Denmark)

    Larsen, Anne Kristine; El-Charnoubi, Waseem-Asim Ghulam; Gehl, Julie;

    2014-01-01

    SUMMARY: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local...... control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence...

  8. Neglected Giant Scalp Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Anne Kristine Larsen, MD

    2014-03-01

    Full Text Available Summary: Rarely, basal cell carcinoma grows to a giant size, invading the underlying deep tissue and complicating the treatment and reconstruction modalities. A giant basal cell carcinoma on the scalp is in some cases treated with a combination of surgery and radiation therapy, resulting in local control, a satisfactory long-term cosmetic and functional result. We present a case with a neglected basal cell scalp carcinoma, treated with wide excision and postoperative radiotherapy, reconstructed with a free latissimus dorsi flap. The cosmetic result is acceptable and there is no sign of recurrence 1 year postoperatively.

  9. Apico-basal polarity complex and cancer

    Indian Academy of Sciences (India)

    Mohammed Khursheed; Murali Dharan Bashyam

    2014-03-01

    Apico-basal polarity is a cardinal molecular feature of adult eukaryotic epithelial cells and appears to be involved in several key cellular processes including polarized cell migration and maintenance of tissue architecture. Epithelial cell polarity is maintained by three well-conserved polarity complexes, namely, PAR, Crumbs and SCRIB. The location and interaction between the components of these complexes defines distinct structural domains of epithelial cells. Establishment and maintenance of apico-basal polarity is regulated through various conserved cell signalling pathways including TGF, Integrin and WNT signalling. Loss of cell polarity is a hallmark for carcinoma, and its underlying molecular mechanism is beginning to emerge from studies on model organisms and cancer cell lines. Moreover, deregulated expression of apico-basal polarity complex components has been reported in human tumours. In this review, we provide an overview of the apico-basal polarity complexes and their regulation, their role in cell migration, and finally their involvement in carcinogenesis.

  10. Automatic basal slice detection for cardiac analysis

    Science.gov (United States)

    Paknezhad, Mahsa; Marchesseau, Stephanie; Brown, Michael S.

    2016-03-01

    Identification of the basal slice in cardiac imaging is a key step to measuring the ejection fraction (EF) of the left ventricle (LV). Despite research on cardiac segmentation, basal slice identification is routinely performed manually. Manual identification, however, has been shown to have high inter-observer variability, with a variation of the EF by up to 8%. Therefore, an automatic way of identifying the basal slice is still required. Prior published methods operate by automatically tracking the mitral valve points from the long-axis view of the LV. These approaches assumed that the basal slice is the first short-axis slice below the mitral valve. However, guidelines published in 2013 by the society for cardiovascular magnetic resonance indicate that the basal slice is the uppermost short-axis slice with more than 50% myocardium surrounding the blood cavity. Consequently, these existing methods are at times identifying the incorrect short-axis slice. Correct identification of the basal slice under these guidelines is challenging due to the poor image quality and blood movement during image acquisition. This paper proposes an automatic tool that focuses on the two-chamber slice to find the basal slice. To this end, an active shape model is trained to automatically segment the two-chamber view for 51 samples using the leave-one-out strategy. The basal slice was detected using temporal binary profiles created for each short-axis slice from the segmented two-chamber slice. From the 51 successfully tested samples, 92% and 84% of detection results were accurate at the end-systolic and the end-diastolic phases of the cardiac cycle, respectively.

  11. Biomarkers for Basal-like Breast Cancer

    OpenAIRE

    Choo, Jennifer R.; Torsten O. Nielsen

    2010-01-01

    Initially recognized through microarray-based gene expression profiling, basal-like breast cancer, for which we lack effective targeted therapies, is an aggressive form of carcinoma with a predilection for younger women. With some success, immunohistochemical studies have attempted to reproduce the expression profile classification of breast cancer through identification of subtype-specific biomarkers. This review aims to present an in depth summary and analysis of the current status of basal...

  12. Basal physiological parameters in domesticated tree shrews (Tupaia belangeri chinensis).

    Science.gov (United States)

    Wang, Jing; Xu, Xin-Li; Ding, Ze-Yang; Mao, Rong-Rong; Zhou, Qi-Xin; Lü, Long-Bao; Wang, Li-Ping; Wang, Shuang; Zhang, Chen; Xu, Lin; Yang, Yue-Xiong

    2013-04-01

    Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine. Multifold advantages such as simplicity of breeding, low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy. Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases. However, basal physiological indexes of tree shrew, especially those related to human disease, have not been systematically reported. Accordingly, we established important basal physiological indexes of domesticated tree shrews including several factors: (1) body weight, (2) core body temperature and rhythm, (3) diet metabolism, (4) locomotor rhythm, (5) electroencephalogram, (6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm. We compared the physiological parameters of domesticated tree shrew with that of rats and macaques. Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃, which was higher than that of rats and macaques; (b) Compared with wild tree shrews, with two activity peaks, domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats, tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews, which matched activity peaks in wild tree shrews. These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

  13. Calcitonin gene-related peptide expression is altered in pulmonary neuroendocrine cells in developing lungs of rats with congenital diaphragmatic hernia

    NARCIS (Netherlands)

    H. IJsselstijn (Hanneke); N. Hung; J.C. de Jongste (Johan); D. Tibboel (Dick); E. Cutz

    1998-01-01

    textabstractCongenital diaphragmatic hernia (CDH) is associated with high neonatal mortality from lung hypoplasia and persistent pulmonary hypertension. Pulmonary neuroendocrine cells (PNEC) produce calcitonin gene-related peptide (CGRP), a potent vasodilator. We previo

  14. 74例老年骨质疏松患者应用鲑鱼降钙素联合阿仑膦酸钠治疗的疗效观察%The observation of the effect of salmon calcitonin combined with alendronate sodium on the treatment of senile osteoporosis

    Institute of Scientific and Technical Information of China (English)

    栾霞; 徐彤; 王学宏; 李荣娟

    2012-01-01

    Objective To evaluate the effect of salmon calcitonin combined with alendronate sodium on bone and joint pain, and to observe the changes of bone mineral density ( BMD) , and the serum concentrations of bone Gla protein (BGP) and calcitonin (CT) in senile osteoporosis patients. Methods Seventy-four senile osteoporosis patients in our hospital were treated with salmon calcitonin combined with alendronate sodium. All of them were given an intramuscular injection of 50 IU salmon calcitonin once every other day. After 15 continuous injections, they were given an oral medication of 1 capsule alendronate sodium once a week. The whole treatment lasted for 6 months. The degree of bone and joint pain before and after treatment was estimated with visual analogue scale (VAS). BMD of the lumbar vertebrae (L2-L4) , the femur neck, and Wards region was tested before and after the treatment. Serum concentrations of BGP and calcitonin were tested before and after the treatment. All the results were statistically analyzed. Results After 6-month treatment with salmon calcitonin combined with alendronate sodium in senile osteoporosis patients, the relief of pain in bone and joint was obvious , and the difference was significant ( P < 0. 01). BMD and the serum concentrations of BGP and calcitonin after the treatment were significantly different from those before the treatment (P < 0. 05 ). Conclusion The treatment with salmon calcitonin combined with alendronate sodium in senile osteoporosis patients can significantly improve BMD and serum concentration of calcitonin, and can reduce the serum concentration of bone Gla protein , relieve bone and joint pain in patients, ameliorate the symptoms, and increase BMD. It has an evident efficacy on senile osteoporosis .%目的 评估联合应用鲑鱼降钙素与阿仑膦酸钠治疗缓解老年性骨质疏松症患者骨关节疼痛及血清骨钙素(BGP)、降钙素(CT)及骨密度(BMD)水平的变化.方法 联合应用鲑鱼降钙素和

  15. Two-dimensional NMR and structure determination of salmon calcitonin in methanol

    Energy Technology Data Exchange (ETDEWEB)

    Meadows, R.P.; Nikonowicz, E.P.; Jones, C.R.; Gorenstein, D.G. (Purdue Univ., Lafayette, IN (USA)); Bastian, J.W.

    1991-02-05

    The structure of the 32-residue peptide salmon calcitonin (sCT) in 90% MeOH-10% H{sub 2}O has been investigated by two-dimensional NMR techniques and molecular modeling. Sequential assignments for nearly all of the 32 spin systems have been obtained, and results indicate that the heptaresidue loop formed by the disulfide bond between Cys-1 and Cys-7 is followed by an {alpha}-helical segment from Val-8 through Tyr-22. A region of conformational heterogeneity is observed for residues 20-25, resulting from the slow isomerism of the cis and trans forms of Pro-23. The C-terminal segment is found to exist in an extended conformation.

  16. Measurement of total body calcium in osteoporotic patients treated with salmon calcitonin

    Energy Technology Data Exchange (ETDEWEB)

    Zanzi, I.; Thompson, K.; Cohn, S.H.

    1981-01-01

    In the past, the evaluation of therapies for osteoporosis has been limited by the lack of a suitable quantitative end point. The introduction of the technique of in vivo total body neutron activation analysis (TBNAA) has made possible the precise and accurate measurement of total body calcium (TBCa). Since almost 99 percent of TBCa is in the skeleton, TBNAA gives a direct measurement of skeletal mass. Thus, changes in skeletal mass serve as an objective criterion in the evaluation of the efficacy of the therapy in osteoporosis. Studies performed at Brookhaven National Laboratory and elsewhere have reported the use of calcitonin (CT) in the treatment of primary osteoporosis and related conditions in a limited number of patients. The physiological effects of CT as an inhibitor of bone resorption has been the rationale of its use. The results of a randomized, controlled, 2 year therapeutical trial of CT in a group of postmenopausal osteoporotic women are presented in this report.

  17. Calcitonin receptors in the rat mesencephalon mediate its analgesic actions: autoradiographic and behavioral analyses

    Energy Technology Data Exchange (ETDEWEB)

    Fabbri, A.; Pert, C.B.; Pert, A.; Fraioli, F.

    1985-09-23

    Autoradiographic analyses of salmon calcitonin (sCT) binding in the rat mesencephalon revealed an exceptionally high concentration of receptors in the ventral and ventrolateral segments of the periaqueductal gray matter (PAG) extending along the entire rostralcaudal axis. Relatively heavy labeling was also seen along a band extending ventrolaterally through the mesencephalic reticular formation. Other receptor-rich areas include the nucleus linearis, pars compacta and lateralis of the substantia nigra, locus coeruleus, parabrachial nuclei and nucleus raphe pontis of the pontine reticular formation. The biological effects are consistent with the potencies of both peptides in displacing SVI-sCT from slide-mounted sections of rat PAG. Naloxone failed to antagonize sCT-induced analgesia, suggesting an opiate independent mechanism for this peptide in elicting analgesia. (Auth.). 60 refs.; 9 figs.

  18. Calcitonin gene-related peptide does not cause the familial hemiplegic migraine phenotype

    DEFF Research Database (Denmark)

    Hansen, J.M.; Thomsen, L.L.; Olesen, J.

    2008-01-01

    Objective: The neuropeptide calcitonin gene-related peptide (CGRP) is a migraine trigger that plays a crucial role in migraine pathophysiology, and CGRP antagonism is efficient in the treatment of migraine attacks. Familial hemiplegic migraine (FHM) is a dominantly inherited subtype of migraine...... without aura. This indicates that the pathophysiologic pathways underlying migraine headache in FHM may be different from the common types of migraine and questions whether CGRP antagonists would be effective in the treatment of FHM patients Udgivelsesdato: 2008/9/9...... with aura associated with several gene mutations. FHM shares many phenotypical similarities with common types of migraine, indicating common neurobiological pathways. We tested the hypothesis that the FHM genotype confers a CGRP hypersensitive phenotype. Methods: We included 9 FHM patients with known...

  19. The Comparison of Effects of Alendronate and Calcitonin Treatment in Men With Osteoporosis

    Directory of Open Access Journals (Sweden)

    Gülcan Gürer

    2004-09-01

    Full Text Available In recent years, there has been a dramatic increase in research investigating the epidemiology, diagnosis, prevention, and treatment of osteoporosis and fragility fractures in men. This study was performed to compare the effects of alendronate and calcitonin treatment in male OP osteoporosis. Thirty men with osteoporosis were enrolled in this study. Bone mineral density (BMD was measured at the proximal femur and lumbar spine by using dual-photon absorptiometry. Thirty men with osteoporosis were randomly divided into two groups. BMD was measured twice as before the treatment and one year later. The end of the treatment a significant improvement was found in the BMD levels of the lomber spine in both groups (p0.05. There was no significant difference of BMD levels of proximal femur when the results were compared either within the groups or between two groups (p>0.05.

  20. Crystal Structure of the DFNKF Segment of Human Calcitonin Unveils Aromatic Interactions between Phenylalanines.

    Science.gov (United States)

    Bertolani, Arianna; Pizzi, Andrea; Pirrie, Lisa; Gazzera, Lara; Morra, Giulia; Meli, Massimiliano; Colombo, Giorgio; Genoni, Alessandro; Cavallo, Gabriella; Terraneo, Giancarlo; Metrangolo, Pierangelo

    2017-02-10

    Although intensively studied, the high-resolution crystal structure of the peptide DFNKF, the core-segment of human calcitonin, has never been described. Here we report how the use of iodination as a strategy to promote crystallisation and facilitate phase determination, allowed us to solve, for the first time, the single-crystal X-ray structure of a DFNKF derivative. Computational studies suggest that both the iodinated and the wild-type peptides populate very similar conformations. Furthermore, the conformer found in the solid-state structure is one of the most populated in solution, making the crystal structure a reliable model for the peptide in solution. The crystal structure of DFNKF(I) confirms the overall features of the amyloid cross-β spine and highlights how aromatic-aromatic interactions are important structural factors in the self-assembly of this peptide. A detailed analysis of such interactions is reported.

  1. Calcitonin gene-related peptide (CGRP) in the nipple of the rat mammary gland

    DEFF Research Database (Denmark)

    Thulesen, J; Rasmussen, T N; Schmidt, P;

    1994-01-01

    The distribution of nerve fibres immunoreactive to calcitonin gene-related peptide (CGRP) was investigated by immunohistochemistry in nipples and mammary glands from lactating and non-lactating rats and compared to the immunoreactivity of other neuropeptides including substance P (SP), neuropeptide...... Y (NPY), vasoactive intestinal peptide (VIP) and somatostatin (SOM). The study revealed an extensive innervation of the mammary nipples, in which CGRP-immunoreactive (IR) nerve fibres were abundantly present in the epidermis, dermal connective tissue and intralobular connective tissue of the mammary...... gland parenchyma. Several of the dermal CGRP-IR fibres seemed to follow blood vessels, or formed "ringlet-like" structures. The latter were mostly observed in the dermal connective tissue of the nipple from the lactating rat and may have a mechanoreceptive function, e.g. for the suckling stimuli...

  2. CALCITONIN GENE-RELATED PEPTIDE INDUCES FIBROBLASTS FROM HIP PSEUDOCAPSULE TO PRODUCE CYTOKINES

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Objective To investigate calcitonin gene-related peptide (CGRP) involvement in the process of aseptic loosening. Methods We isolated fibroblasts from periprosthetic pseudocapsular tissue at the time of revision hip arthroplasty performed due to aseptic loosening. Fibroblasts were incubated for 24 h in the presence of CGRP, and the levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α in the media were determined using enzyme-linked immunosorbent assay kit. Results We found that the levels of IL-1β, IL-6, and TNF-α increased in a time- and concentration-dependent manner. ConclusionThese inflammatory cytokines play an important role in the development of periprosthetic osteolysis and implant loosening. Our results suggest that CGRP may be involved in the pathogenesis of aseptic loosening.

  3. A sup 1 H NMR study of human calcitonin in solution

    Energy Technology Data Exchange (ETDEWEB)

    Motta, A. (Consiglio Nazionale delle Richerche, Napoli (Italy)); Temussi, P.A. (Univ. di Napoli (Italy)); Wuensch, E.; Bovermann, G. (Max-Planck-Inst. fuer Biochemie, Martinsried bei Muenchen (West Germany))

    1991-03-05

    Human calcitonin (hCT) has been investigated by NMR at 400 MHz in DMSO{sub d6} and in an 85% DMSO{sub d6}-15% {sup 1}H{sub 2}O (v/v) cryoprotective mixture. All backbone and side-chain resonances have been assigned and the secondary structure has been determined in both solvents. In DMSO{sub d6}, the simultaneous presence of d{sub {alpha}N}, d{sub NN}, and some specific weak medium-range nuclear Overhauser effects, together with the amide temperature coefficients and the analysis of the NH-{alpha}CH spin-spin coupling constants, indicates that hCT is highly flexible but with three domains (comprising segments Asn{sup 3}-Gly{sup 10}, Gln{sup 14}-Thr{sup 21}, and Thr{sup 25}-Ala{sup 31}) in extended conformations which dynamically transform into isolated {beta} turns in the N- and C-terminal regions and into adjacent tight turns, resembling a 3{sub 10} helix structure, in the central part. The DMSO-water mixture rigidifies the polypeptide chain, favoring and ordered, extended conformation. NOESY data indicate the presence of a short double-stranded antiparallel {beta} sheet in the central region made by residues 16-21 and connected by a two-residue hairpin loop formed by residues 18 and 19. Two tight turns, formed by residues 3-6 and 28-31, were also identified. The central {beta} sheet does not favor an amphipathic distribution of the residues as found for salmon calcitonin. This is in agreement with the smaller tendency of hCT to form the amphipathic {alpha} helix, postulated to be responsible for the interaction of hCT with lipids. The possible role of the cis-trans isomerism of Pro is discussed.

  4. Metal ions as cofactors for aggregation of therapeutic peptide salmon calcitonin.

    Science.gov (United States)

    Rastogi, Neeraj; Mitra, Kalyan; Kumar, Dinesh; Roy, Raja

    2012-05-21

    The effects of multivalent metal ions (Cu(2+)/Zn(2+)/Al(3+)) on the aggregation of salmon calcitonin (sCT)--a therapeutic peptide used worldwide in the treatment of osteoporosis and Paget's disease--have been studied in vitro using NMR (both solution state and solid state), TEM, ThT-fluorescence, and FT-IR spectroscopy. Overall, the various results indicated that the metal-ions-induced conformational transitions in the peptide--mostly toward the β-sheet--facilitate the aggregation of sCT in solution. First, the solution NMR has been used to check the interaction between the peptide and the metal ions. Following this, the formation and characterization of calcitonin aggregates has been performed using TEM, solid state NMR, and FT-IR spectroscopy. The TEM and ThT-fluorescence results revealed that the sCT peptide incubated with Cu(2+) and Zn(2+) metal ions (in aqueous environment) forms globular aggregates, while that with Al(3+) ions forms fibrils. The solid state NMR and FT-IR studies revealed the presence of a substantial amount of β-sheet content in sCT aggregates (formed in the presence of these metal ions) compared to the monomeric sCT, indicating that the metal binding is concomitant with conformational changes. The present study becomes crucial while prescribing this drug peptide under physio-pathological conditions associated with an abnormal accumulation of metal ions (Cu(2+)/Zn(2+)/Al(3+)) in the body (i.e., abnormal metal ion homeostasis).

  5. Localized basal meningeal enhancement in tuberculous meningitis

    Energy Technology Data Exchange (ETDEWEB)

    Theron, Salomine; Andronikou, Savvas; Grobbelaar, Marie; Steyn, Freda; Mapukata, Ayanda; Plessis, Jaco du [University of Stellenbosch, Department of Radiology, Tygerberg Hospital, P.O. BOX 19063, Tygerberg (South Africa)

    2006-11-15

    Focal basal meningeal enhancement may produce a confusing CT picture in children with suspected tuberculous meningitis (TBM). To demonstrate the incidence, distribution and appearance of localized basal meningeal enhancement in children with TBM. CT scans of patients with definite (culture proven) and probable (CSF suggestive) TBM were retrospectively evaluated by two observers. Localized basal enhancement was documented as involving: unilateral cistern of the lateral fossa (CLF), unilateral sylvian fissure, unilateral CLF and sylvian fissure in combination, unilateral CLF and sylvian fissure with ipsi- or contralateral ambient cistern and isolated quadrigeminal plate cistern. The study included 130 patients with TBM (aged 2 months to 13 years 9 months). Focal basal enhancement was seen in 11 patients (8.5%). The sylvian fissure was involved most commonly, followed by the lateral fossa cistern. The ambient cistern was involved in three patients and the quadrigeminal plate cistern in one. Focal areas of enhancement corresponded to the areas of infarction in every patient. Focal basal meningeal enhancement is common (8.5%) in paediatric TBM. This must be kept in mind when evaluating CT scans in children presenting with focal neurological findings, seizures or meningism in communities where TBM is endemic. (orig.)

  6. Somatotopic organization of the primate basal ganglia

    Directory of Open Access Journals (Sweden)

    Atsushi eNambu

    2011-04-01

    Full Text Available Somatotopic organization is a fundamental and key concept to understand how the cortico-basal ganglia loop works. It is also indispensable knowledge to perform stereotaxic surgery for movement disorders. Here I would like to describe the somatotopic organization of the basal ganglia, which consist of the striatum, subthalamic nucleus, globus pallidus and substantia nigra. Projections from motor cortical regions representing different body parts terminate in different regions of these nuclei. Basal ganglia neurons respond not only to the stimulation of the corresponding regions of the motor cortices, but also to active and passive movements of the corresponding body parts. On the basis of these anatomical and physiological findings, somatotopic organization can be identified in the motor territories of these nuclei in the basal ganglia. In addition, projections from functionally interrelated cortical areas partially converge through the cortico-basal ganglia loop, but nevertheless the somatotopy is still preserved. Disorganized somatotopy may explain, at least in part, the pathophysiology of movement disorders, such as Parkinson’s disease and dystonia.

  7. Identification of triple-negative and basal-like canine mammary carcinomas using four basal markers.

    Science.gov (United States)

    Kim, N H; Lim, H Y; Im, K S; Kim, J H; Sur, J-H

    2013-05-01

    Molecular-based classification of canine mammary carcinomas (CMCs) has been a recent research focus. In human breast cancer, triple-negative and basal-like phenotypes are distinct molecular subgroups that are known for their poor prognosis, but these tumours are not yet well defined in the dog. The aim of this study was to determine whether CMCs include triple-negative and basal-like phenotypes by immunohistochemical assessment of expression of the oestrogen receptor (OR), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and four basal markers, cytokeratin (CK) 14, CK5/6, p63 and the epidermal growth factor receptor (EGFR). In this study of 241 CMCs, 45 triple-negative tumours (OR(-), PR(-) and HER2(-)) were identified and this phenotype was associated with an unfavourable prognosis. In these tumours, the expression of CK14, CK5/6 and EGFR was related to clinicopathological parameters, while the expression of p63 was not relevant. The majority of the triple-negative tumours were of the basal-like phenotype, given that 75.6% of them expressed more than two basal markers. However, three of the basal markers were not uniformly expressed; therefore, the proportion of the basal-like phenotype was altered on the basis of the selection of the markers. Although both triple-negative and basal-like phenotypes are distinct entities in CMC, further study is needed to differentiate one from the other.

  8. Insights into interactions between the alpha-helical region of the salmon calcitonin antagonists and the human calcitonin receptor using photoaffinity labeling.

    Science.gov (United States)

    Pham, Vi; Dong, Maoqing; Wade, John D; Miller, Laurence J; Morton, Craig J; Ng, Hooi-Ling; Parker, Michael W; Sexton, Patrick M

    2005-08-05

    Fish-like calcitonins (CTs), such as salmon CT (sCT), are widely used clinically in the treatment of bone-related disorders; however, the molecular basis for CT binding to its receptor, a class II G protein-coupled receptor, is not well defined. In this study we have used photoaffinity labeling to identify proximity sites between CT and its receptor. Two analogues of the antagonist sCT(8-32) containing a single photolabile p-benzoyl-l-phenylalanine (Bpa) residue in position 8 or 19 were used. Both analogues retained high affinity for the CT receptor and potently inhibited agonist-induced cAMP production. The [Bpa(19)]sCT(8-32) analogue cross-linked to the receptor at or near the equivalent cross-linking site of the full-length peptide, within the fragment Cys(134)-Lys(141) (within the amino terminus of the receptor, adjacent to transmembrane 1) (Pham, V., Wade, J. D., Purdue, B. W., and Sexton, P. M. (2004) J. Biol. Chem. 279, 6720-6729). In contrast, proteolytic mapping and mutational analysis identified Met(49) as the cross-linking site for [Bpa(8)]sCT(8-32). This site differed from the previously identified cross-linking site of the agonist [Bpa(8)]human CT (Dong, M., Pinon, D. I., Cox, R. F., and Miller, L. J. (2004) J. Biol. Chem. 279, 31177-31182) and may provide evidence for conformational differences between interaction with active and inactive state receptors. Molecular modeling suggests that the difference in cross-linking between the two Bpa(8) analogues can be accounted for by a relatively small change in peptide orientation. The model was also consistent with cooperative interaction between the receptor amino terminus and the receptor core.

  9. Radiologic study of basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Park, Tae Won [Dept. of Oral Radiology, College of Dentistry, Seoul National University, Seoul (Korea, Republic of)

    1988-11-15

    Several cases of jaw cyst-basal cell nevus-bifid rib syndrome are presented. This syndrome consists principally of multiple jaw cysts, basal cell nevi, and bifid ribs but no one component is present in all patients. The purpose of this paper is to review the multiple characteristics of this syndrome and present three cases in a family and additional 4 cases. The many malformations associated with the syndrome have variable expressively. In the cases, multiple jaw cysts, pal mar and plantar pittings, bridging of sella, temporoparietal bossing, hypertelorism, cleft palate, and dystopia canthoru m have been observed.

  10. Calcitonin Gene-Related Peptide Modulates Heat Nociception in the Human Brain - An fMRI Study in Healthy Volunteers

    DEFF Research Database (Denmark)

    Asghar, Mohammad Sohail; Becerra, Lino; Larsson, Henrik B W

    2016-01-01

    BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we record...... cortex. Sumatriptan injection reversed these changes. CONCLUSION: The changes in BOLD-signals in the brain after CGRP infusion suggests that systemic CGRP modulates nociceptive transmission in the trigeminal pain pathways in response to noxious heat stimuli.......BACKGROUND: Intravenous infusion of calcitonin-gene-related-peptide (CGRP) provokes headache and migraine in humans. Mechanisms underlying CGRP-induced headache are not fully clarified and it is unknown to what extent CGRP modulates nociceptive processing in the brain. To elucidate this we recorded...

  11. The Effect of Alendronate and Calcitonin Treatments on Bone Mineral Density and Quality of Life in Women With Postmenopausal Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2002-06-01

    Full Text Available The aim of this study was to compare the effect of alendronate and calcitonin treatments on bone mineral density (BMD and quality of life of women with postmenopausal osteoporosis. One hundred ninety-three patients were randomly assigned to two groups: 93 patients received daily doses of 10 mg alendronate and calcium 1000 mg, and 98 patients used intranasal salmon calcitonin (sCt at a dosage of 200 IU/day and they also received daily doses of 1000 mg calcium supplements. DXA was used for the measurement of BMD of the lumbar spine and proximal femur before and after the study period. SF-36 was used as a measure of health-related quality of life. At the end of the treatment, ALN produced significant increases in BMD at the lumbar spine (p< 0.001, femur neck (p<0.05, trochanteric region (p<0.001 and at the Ward triangle (p<0.05. In contrast, intranasal sCt treatment resulted in a significant bone loss in the femur neck (p<0.01 and Ward triangle (p<0.05, and only a significant increase in BMD of the lumbar spine was observed with calcitonin treatment(p< 0.05. Quality of life as assessed by SF-36 improved significantly in both groups(p<0.05. In conclusion, alendronate seemed to be more effective than calcitonin, increasing both spinal and femoral BMD, for the treatment of postmenopausal osteoporosis. Both treatments were found to be effective for the improvement of quality of life.

  12. Protective effect of calcitonin on lumbar fusion-induced adjacent-segment disc degeneration in ovariectomized rat

    OpenAIRE

    Liu, Chang-Cheng; Tian, Fa-Ming; Zhou, Zhuang; Wang, Peng; Gou, Yu; Zhang, Heng; Wang, Wen-Ya; Shen, Yong; Zhang, Ying-Ze; Zhang, Liu

    2015-01-01

    Background Intervertebral disc (IVD) degeneration and pathological changes in the spinal cord are major causes of back pain. In addition to its well-established anti-resorptive effect on bone, calcitonin (CT) potentially exerts protective effects on IVD degeneration in ovariectomized rats. However, possible therapeutic effects of CT on lumbar fusion-induced adjacent-segment disc degeneration (ASDD) have not been investigated yet. In this study, we examined the effects of CT on IVD degeneratio...

  13. RELATIONSHIP BETWEEN THE PATTERN OF METHYLATION OF CALCITONIN GENE AND ACTIVITY OF METHYLTRANSFERASE in 8 Tumor Cell Lines

    Institute of Scientific and Technical Information of China (English)

    BAI; Zhi-yong

    2001-01-01

    [1]Baylin SB, Fearon ER, Vogeletein B, et al. Hyper- methylation of 5' the region of the calcitonin gene is a property of human lymphoid and acute myeloid malignancies [J]. Blood 1987; 70:412.[2]Nelkin BD, Przepiorka D, Burke PJ, et al. Abnormal methylation of the calcitonin gene marks progression of chronic myelogenous leukemia [J]. Blood 1991; 77: 2431.[3]Ritter M, Kant EDe, Huhn D, et al. Detection of DNA methylation in the calcitonin gene in human leukemias using differential polymerase chain reaction [J]. Leukemia 1995; 9:915.[4]Wu SL, Xie GL, Bai RK, et al. Semi-quantitative study of calcitonin gene methylation in myelodysplastic syndrome [J]. Chin Med J 1998; 111:690.[5]Admas RL, Rinaldi A, Seivwright CA. Microassay for DNA methyltranferase [J]. J Biochem Biophys Methods 1991; 22:19.[6]Bai ZY, Xu GB, Wu SL. Detection of DNA- methyl- tranferase activity of leukemia cells with radiology microassay [J]. J Beijing Med Univ 2000; 32:76.[7]Issa J, Veritino PM, Wu J, et al. Increased cytosine DNA- Methyltranferase activity during colon cancer pro- gression [J]. J Natl Cancer Inst 1993; 85:1235.[8]Vertino PM, Yen RW, Gao J, et al. De novo methylation of CpG islands sequences in human fibroblasts overexpression DNA (cytosine-5-) methyltranferase [J]. Mol cell Bio 1996; 16:4555.[9]Robertson KD, Uzvolgyi E, Liang G, et al. The human DNA methyltranferase (DNMTs) 1, 3a and 3b: coordinate mRNA expression in normal tissue and overexpression in tumors [J]. Nucleic Acids Res 1999; 27:2291.[10]Okano M, Bell DW, Haber DA, et al. DNA methyl- tranferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development [J]. Cell 1999; 99:247.

  14. 鲑鱼降钙素促进老年转子间骨折愈合的疗效观察%Efficacy Observation of Salmon Calcitonin for Femoral Intertrochanteric Fractures Healing in Elderly Patients

    Institute of Scientific and Technical Information of China (English)

    谭美云; 郭杏; 税巍; 王远辉; 张忠杰

    2011-01-01

    目的:观察鲑鱼降钙素促进老年转子问骨折愈合的疗效.方法:将40例老年患者随机分为2组:治疗组20例,肌肉注射鲑鱼降钙素;对照组20例,在相同的部位肌肉注射等量注射用生理盐水.自术后第1天开始,2组均连续用药3个月.用药后的第1、3个月复查X线片,观察骨痂生长情况.治疗前和治疗后3个月检测患者腰椎(L4)骨密度(BMD)及血清钙、磷、碱性磷酸酶等浓度.结果:所有患者均得到随访.术后第1、3个月x线评估发现,治疗组比同时期对照组的骨痂生成量多.治疗后3个月,治疗组腰椎(L4)BMD明显高于对照组(P0.05),治疗组碱性磷酸酶明显高于对照组(P<0.05).治疗组1例出现恶心、呕吐等胃肠道症状,2例出现面颈部潮红.结论:鲑鱼降钙素能显著促进老年转子间骨折的愈合.%OBJECTIVE: To observe the therapeutic efficacy of salmon calcitonin for femoral intertrochanteric fractures healing in elderly patients. METHODS: A total of 40 elderly patients with femoral intertrochanteric fractures were randomly divided into 2 groups. 20 cases in treatment group received intramuscular injection of salmon calcitonin and 20 cases in control group received equal dose of normal saline at the same site. Both groups were given medicine after operation for 3 months. The X-ray plate of 2 groups was examined at 1 and 3 months after treatment to investigate the condition of bony callus. The BMD of the lumbar spine at LA, the concentration of serum calcium, serum phosphorus and alkaline phosphate were measured before treament and 3 months after treatment. RESULTS: All patients were followed up. The X-ray plate showed that the bony callus in treatment group was more abundant than in control group at 1 and 3 months after treatment. 3 months after treatment, the BMD of the lumbar spine at L4 in treatment group was significantly higher than in control group (P<0.05). The concentration of serum calcium in treatment group was

  15. Development of Calcitonin Salmon Nasal Spray: similarity of peptide formulated in chlorobutanol compared to benzalkonium chloride as preservative.

    Science.gov (United States)

    Costantino, Henry R; Culley, Heather; Chen, Lishan; Morris, Daniel; Houston, Michael; Roth, Sharin; Phoenix, Mary Jo; Foerder, Chuck; Philo, John S; Arakawa, Tsutomu; Eidenschink, Lisa; Andersen, Niels H; Brandt, Gordon; Quay, Steven C

    2009-10-01

    The similarity of an intranasal salmon calcitonin (sCT) employing chlorobutanol as preservative (Calcitonin Salmon Nasal Spray) was compared to the reference listed drug (RLD) employing benzalkonium chloride as preservative (Miacalcin Nasal Spray). Various orthogonal methods assessed peptide structuring, dynamics, and aggregation state. Mass spectrometry, amino acid analysis, and N-terminal sequencing all demonstrated similarity in primary structure. Near- and far-UV circular dichroism (CD) data supported similarity in secondary and tertiary sCT structure. Nuclear magnetic resonance studies further supported similarity of three-dimensional structure and molecular dynamics of the peptide. Other methods, such as sedimentation velocity and size exclusion chromatography, demonstrated similarity in peptide aggregation state. These latter methods, in addition to reversed phase chromatography, were also employed for monitoring stability under forced degradation, and at the end of recommended shelf storage and patient use conditions. In all cases and for all methodologies employed, similarity to the RLD was observed with respect to extent of aggregation and other degradation processes. Finally, ELISA and bioassay data demonstrated similarity in biological properties. These investigations comprehensively demonstrate physicochemical similarity of Calcitonin Salmon Nasal Spray and the RLD, and should prove a useful illustration to pharmaceutical scientists developing alternative and/or generic peptide or protein products.

  16. The Effect of Alendronate and Intranasal Calcitonin Treatments on Bone Mineral Density in Men with Idiopathic Osteoporosis

    Directory of Open Access Journals (Sweden)

    F. Taşçıoğlu

    2003-03-01

    Full Text Available The aim of this study was to compare the effect of alendronate and calcitonin treatments on bone mineral density (BMD in men with idiopathic osteoporosis. After performing a detailed clinical and laboratory assessment in order to eliminate secondary factors that can lead to osteoporosis, fifty-two men with idiopathic osteoporosis were randomly assigned to two groups: 28 patients in the first group received intranasal salmon calcitonin at a dosage of 200 IU/ day and they also received daily doses of 1000 mg calcium supplements. Twenty-four patients in the second group used 10 mg alendronate/day and 1000 mg calcium/day. DXA was used for the measurement of BMD of the lumbar spine and proximal femur before and after the study period. At the end of the treatment, alendronate produced significant increases in BMD at the lumbar spine (p0.05. When the groups were compared with each other, a significant increase in lumbar BMD was obtained in favor of alendronate treatment (p<0.05. In conclusion, alendronate seemed to be more effective than calcitonin, increasing both spinal and femoral BMD, for the treatment of idiopathic male osteoporosis.

  17. Calcitonina monomérica plasmática e hipercalcemia em pacientes portadores de neoplasia pulmonar Monomeric plasmatic calcitonin and hypercalcemia in lung cancer patients

    Directory of Open Access Journals (Sweden)

    R. Coifman

    1997-06-01

    lung cancer, and its correlation with hypercalcemia, a very common complication in these tumors. METHOD. Blood were sampled from 56 patients with malignant lung disease for the CT and ionized calcium determinations. Calcitonin was measured using a specific radioimmunoassay for the monomeric form of the molecule, in a previous silica extracted serum probe. RESULTS. We did not find elevated levels of monomeric CT in lung cancer. Only 3 patients had mild elevated levels, while in the others CT was normal or undetectable. Hypercalcemia was found in 21.4% of these patients, but only one with supranormal CT levels. CONCLUSION. Monomeric CT serum levels are normal in lung cancer, what makes the latter use an unreliable tumor marker.

  18. Basal Cell Carcinoma in The Netherlands

    NARCIS (Netherlands)

    S.C. Flohil (Sophie)

    2012-01-01

    textabstractThere are many different cutaneous malignancies, but malignant melanoma, squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent approximately 98% of all skin cancers.In literature, these three skin cancers are often divided into melanoma and nonmelanoma skin cancers (NMSC

  19. Immunosuppressive Environment in Basal Cell Carcinoma

    DEFF Research Database (Denmark)

    Omland, Silje H; Nielsen, Patricia S; Gjerdrum, Lise M R;

    2016-01-01

    Interaction between tumour survival tactics and anti-tumour immune response is a major determinant for cancer growth. Regulatory T cells (T-regs) contribute to tumour immune escape, but their role in basal cell carcinoma (BCC) is not understood. The fraction of T-regs among T cells was analysed...

  20. Parallel basal ganglia circuits for decision making.

    Science.gov (United States)

    Hikosaka, Okihide; Ghazizadeh, Ali; Griggs, Whitney; Amita, Hidetoshi

    2017-02-02

    The basal ganglia control body movements, mainly, based on their values. Critical for this mechanism is dopamine neurons, which sends unpredicted value signals, mainly, to the striatum. This mechanism enables animals to change their behaviors flexibly, eventually choosing a valuable behavior. However, this may not be the best behavior, because the flexible choice is focused on recent, and, therefore, limited, experiences (i.e., short-term memories). Our old and recent studies suggest that the basal ganglia contain separate circuits that process value signals in a completely different manner. They are insensitive to recent changes in value, yet gradually accumulate the value of each behavior (i.e., movement or object choice). These stable circuits eventually encode values of many behaviors and then retain the value signals for a long time (i.e., long-term memories). They are innervated by a separate group of dopamine neurons that retain value signals, even when no reward is predicted. Importantly, the stable circuits can control motor behaviors (e.g., hand or eye) quickly and precisely, which allows animals to automatically acquire valuable outcomes based on historical life experiences. These behaviors would be called 'skills', which are crucial for survival. The stable circuits are localized in the posterior part of the basal ganglia, separately from the flexible circuits located in the anterior part. To summarize, the flexible and stable circuits in the basal ganglia, working together but independently, enable animals (and humans) to reach valuable goals in various contexts.

  1. Giant basal cell carcinoma Carcinoma basocelular gigante

    Directory of Open Access Journals (Sweden)

    Nilton Nasser

    2012-06-01

    Full Text Available The basal cell carcinoma is the most common skin cancer but the giant vegetating basal cell carcinoma reaches less than 0.5 % of all basal cell carcinoma types. The Giant BCC, defined as a lesion with more than 5 cm at its largest diameter, is a rare form of BCC and commonly occurs on the trunk. This patient, male, 42 years old presents a Giant Basal Cell Carcinoma which reaches 180 cm2 on the right shoulder and was negligent in looking for treatment. Surgical treatment was performed and no signs of dissemination or local recurrence have been detected after follow up of five years.O carcinoma basocelular é o tipo mais comum de câncer de pele, mas o carcinoma basocelular gigante vegetante não atinge 0,5% de todos os tipos de carcinomas basocelulares. O Carcinoma Basocelular Gigante, definido como lesão maior que 5 cm no maior diâmetro, é uma forma rara de carcinoma basocelular e comumente ocorre no tronco. Este paciente apresenta um Carcinoma Basocelular Gigante com 180cm² no ombro direito e foi negligente em procurar tratamento. Foi realizado tratamento cirúrgico e nenhum sinal de disseminação ou recorrência local foi detectada após 5 anos.

  2. Synthesis, characterization and in vitro evaluation of a bone targeting delivery system for salmon calcitonin.

    Science.gov (United States)

    Bhandari, Krishna Hari; Newa, Madhuri; Uludag, Hasan; Doschak, Michael R

    2010-07-15

    Synthetic salmon Calcitonin (sCT) is currently used to treat and manage conditions associated with low bone mass, and elicits its antiresorptive effect by acting upon Calcitonin receptors (CTRs) located on bone-resorbing osteoclast cells. However, CTRs are also widely distributed in many non-skeletal tissues (such as kidney, brain, and lung), and the competitive uptake of available sCT amongst such CTRs likely reduces sCT availability for bone resident osteoclast cells, particularly if the drug is administered systemically and not specifically targeted to bone. Hence, the objective of this study was to synthesize and characterize a bisphosphonate (BP)-mediated bone targeting delivery system for sCT and to determine whether the bioactivity of sCT was retained after BP conjugation. BP-sCT conjugates were synthesized by initially reacting sCT with sulfosuccinimidyl-4-[N-maleimidomethyl]cyclohexane-1-carboxylate (sulfo-SMCC) in dimethyl formamide in the presence of triethylamine (TEA) at room temperature. Thiolated (Thiol)-BP was then reacted with the sCT-sulfo-SMCC conjugates to generate sCT-BP conjugates, which were purified by dialysis and assayed using the micro-BCA protein assay. Non-BP containing control sCT-Cysteine conjugates were also synthesized using the same procedure. Reactions were monitored and characterized using matrix-assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF) analysis and Tris-Tricine SDS-PAGE. Conjugates were evaluated for in vitro bone mineral affinity using a hydroxyapatite binding test, for bone mineral specificity using different calcium salt binding affinity assays, and for continued sCT bioactivity after conjugation using an intracellular cAMP stimulation in human T47D breast cancer cells. Our results confirmed that BP-conjugated sCT exhibited significantly greater affinity and specificity for bone mineral over unmodified sCT, and that sCT-BP conjugates retained strong CT bioactivity after conjugation

  3. Effect of Busheng Zhuanggu Formula and Salmon Calcitonin on Elderly Osteoporosis%补肾壮骨方联合鲑鱼降钙素治疗老年骨质疏松症临床观察

    Institute of Scientific and Technical Information of China (English)

    李德梅; 蔡莉莉; 李丽娜; 李敬会; 夏忠诚; 余武

    2011-01-01

    Objective To study the clinical effect of Busheng Zhuanggu formula and salmon calcitonin on elderly osteoporosis.Methods One hundred cases of elderly with osteoporosis were randomly divided into trial group and control group.Patients in control group were treated with calcitonin and calcium supplement with Vitamine-D Chewable Tablets, and patients in trial group were treated with Busheng Zhuanggu formula and salmon calcitonin additionally.The bone mineral density (BMD) and BGP, TRAP,HYP of two groups before and after treatment were observed.Results In treatment group and in control group, BMD of lumber vertebrae (L2-4) and neck of femur increased significantly after three month treatment compared with control group (P >0.05), but no significant change in the region of Wards.The remission rate of osteodynia was 98.60% in trial group and 71.42% in control groups (P<0.05).The level of serum BGP increased in trial group and the ratio of urinary HYP/Cr decreased, with significant difference between the two groups (P <0.05).Conclusion The combining treatment of salmon calcitonin and Busheng Zhuanggu formula on elderly osteoporosis can relieve the osteodynia and increase bone mass.%目的 探讨补肾壮骨方联合鲑鱼降钙素对老年骨质疏松症的临床疗效.方法 选择100例老年骨质疏松症患者,随机分为观察组和对照组.2 组均服用维D钙咀嚼片,对照组静脉点滴骨肽针,观察组在对照组治疗基石出上肌注鲑鱼降钙素针、口服补肾壮骨方,疗程均为3个月.观察2组治疗前后骨密度及骨钙素(BGP)、血抗酒石酸酸性磷酸酶(TRAP)、尿羟脯氨酸(HYP)等指标的变化.结果 治疗3个月后,2组腰推、股骨预部的骨密度较治疗前均有升高,而治疗组升高更明显,2组比较差异有统计学意义(P<0.05),Ward:区骨密度无显著性改变;观察组骨痛总有效率为98.60%,对照组为71.42%(P<0.05);2组血BGP水平治疗后呈增高的改变,血TRAP水平和尿HYP

  4. The effects of synthetic salmon calcitonin on thyroid C and follicular cells in adult female rats

    Directory of Open Access Journals (Sweden)

    M. Manojlovic-Stojanoski

    2011-08-01

    Full Text Available Structural and morphometric features of thyroid C and follicular cells were studied in adult rat females after treatment with synthetic salmon calcitonin (CT. The animals were chronically treated with either a low (10 IU/kg b.w or a high (100 IU/kg b.w dose of CT. A stereological method was applied to determine the volume density and the number of immunoreactive C cells. The height and volume density of follicular epithelium, colloid, interstitium and the follicles (epithelium plus colloid, as well as the index of activation rate were calculated. A significant decrease in body weight, as well as the volume density of immunoreactive C cells and the number of C cells per mm2, was observed in rats treated with both doses of CT. The height and volume density of follicular epithelium and follicles, as well as the index of activation rate were significantly increased in the animals given the high CT dose, while the volume densities of colloid and interstitium were reduced. No significant changes in the examined morphometric parameters were detected after treatment with the low CT dose. According to these results it can be concluded that the structural features of thyroid C and follicular cells were affected by the high dose CT treatment in the opposite manner, while the low dose CT treatment influenced only C cells.

  5. Relationship between internalization and calcitonin-induced receptor loss in T 47D cells

    Energy Technology Data Exchange (ETDEWEB)

    Findlay, D.M.; Martin, T.J.

    1984-07-01

    Exposure of T 47D human breast cancer cells to salmon calcitonin (sCT) resulted in a reduction of binding capacity for (/sup 125/I)iodo-sCT in washed cells. The reduction was both time and concentration dependent. Recovery of binding capacity in CT-pretreated T 47D cells occurred in the absence of CT, but was prevented by inhibitors of protein synthesis. Studies were carried out to determine the mechanism of CT-induced reduction of binding capacity. It was found that at 37/sup 0/ C sCT induced a time-dependent loss of cell surface receptors, so that initially the lost binding capacity was largely reclaimable by acid treatment, whereas after longer exposure to sCT, acid treatment was much less effective in regenerating binding capacity. The CT-induced reduction in binding capacity was not observed when cells were pretreated with sCT at 4 C or in the presence of inhibitors of cellular metabolic energy. These results are consistent with the view that initially CT-induced loss of CT receptors in T 47D cells is primarily due to occupancy of cell-surface receptors and later to a reduction in the concentration of cell-surface receptors mediated by an energy requiring internalization process involving the CT-receptor complex; reappearance of receptors requires new protein synthesis.

  6. Formulation and evaluation of novel reverse microemulsions containing salmon calcitonin in hydrofluoroalkane propellants.

    Science.gov (United States)

    Shan, Ziyun; Tan, Yinhe; Qin, Lingzhen; Li, Ge; Pan, Xin; Wang, Zhouhua; Yu, Xiu; Wang, Qinruo; Wu, Chuanbin

    2014-05-15

    To develop reverse microemulsion as a potential strategy for pulmonary delivery of salmon calcitonin (sCT) in HFA134a propellant of pressurized metered dose inhalers (pMDIs), pluronic P85 (P85) was chosen as the most appropriate surfactant to form microemulsions containing sCT. Formulation parameters, including the surfactant and ethanol content, water content, and sCT loading, were optimized to obtain two desired pMDI formulations A and B with clear and transparent appearance, Tyndall effect, good physical stability and aerosolization properties. Aerosolization properties of the optimized pMDIs were assessed by next generation impactor (NGI) and twin-stage impactor (TSI), and the dose of sCT in each stage was assayed by HPLC. The fine particle fraction (FPF) of formulations A and B were both at the range of approximately 28.0-36.0%. Cytotoxicity studies indicated the cell viability determined by MTT assay only slightly dropped when the A549 cells were exposed to the pMDI formulations. Pharmacological study performed on the male Wistar rats showed the intratracheal administration of the microemulsion pMDIs containing sCT exhibited similar but prolonged hypocalcemic activity compared with the intravenous injection of sCT solution. Therefore, such reverse microemulsions are potential for pulmonary delivery of therapeutic peptides using HFA-pMDIs.

  7. Colonic absorption of salmon calcitonin using tetradecyl maltoside (TDM) as a permeation enhancer.

    Science.gov (United States)

    Petersen, Signe Beck; Nielsen, Lisette Gammelgaard; Rahbek, Ulrik Lytt; Guldbrandt, Mette; Brayden, David J

    2013-03-12

    Calcitonin is used as a second line treatment of postmenopausal osteoporosis, but widespread acceptance is somewhat limited by subcutaneous and intranasal routes of delivery. This study attempted to enable intestinal sCT absorption in rats using the mild surfactant, tetradecyl maltoside (TDM) as an intestinal permeation enhancer. Human Caco-2 and HT29-MTX-E12 mucus-covered intestinal epithelial monolayers were used for permeation studies. Rat in situ intestinal instillation studies were conducted to evaluate the absorption of sCT with and without 0.1 w/v% TDM in jejunum, ileum and colon. TDM significantly enhanced sCT permeation across intestinal epithelial monolayers, most likely due to combined paracellular and transcellular actions. In situ, TDM caused an increased absolute bioavailability of sCT in rat colon from 1.0% to 4.6%, whereas no enhancement increase was observed in ileal and jejunal instillations. Histological analysis suggested mild perturbation of colonic epithelia in segments instilled with sCT and TDM. These data suggest that the membrane composition of the colon is different to the small intestine and that it is more amenable to permeation enhancement. Thus, formulations designed to release payload in the colon could be advantageous for systemic delivery of poorly permeable molecules.

  8. Study of the action of calcitonin by its effects on lead-induced hypercalcemia. [Rats

    Energy Technology Data Exchange (ETDEWEB)

    Talmage, R.V.; VanderWiel, C.J.

    1979-01-01

    Intravenous (i.v.) injection of lead acetate produces an immediate elevation in total plasma calcium and phosphate levels. This is due to the formation of calcium-phosphate compounds which can be removed by centrifugation at 25,000 x g. For this study, the effect of salmon calcitonin (CT) on these lead-induced plasma changes was studied. Intact male rats were injected i.v. with lead acetate 10 to 30 mg/kg. CT (0.1 to 0.2 mU/g) injected 30 min prior to lead modified the lead-induced plasma changes as follows: the concentration of lead remaining in plasma was statistically reduced. This was accompanied by a decrease in the amount of colloidal calcium-phosphate removed by ultracentrifugation and a corresponding decrease in the lead-induced elevation of total plasma calcium and phosphate levels. This action of CT was still effective in acutely nephrectomized rats. However, a 15-day pretreatment with a diphosphonate abolished the hypocalcemic effect of CT and also abolished the ability of CT to affect the lead-induced plasma changes. Finally, CT was ineffective if injected in as short a time period as 30 min after lead injection. It is concluded from these studs that CT causes a rapid sequestering of lead from plasma into specific sites in bone.

  9. Metabolism of radioiodinated salmon calcitonin in rats. [/sup 125/I tracer technique

    Energy Technology Data Exchange (ETDEWEB)

    Scarpace, P.J.; Neuman, W.F.; Raisz, L.G.

    1977-05-01

    Synthetic salmon calcitonin (CT) was iodinated by an electrolytic method. The iodinated hormone retained full biological activity as determined in both an in vivo and in vitro bioassay. The metabolism of this hormone was studied in rats of two different ages, 24 days and 8 months old. Two types of uptake were observed: Rapid accumulation followed by rapid loss or degradation, as represented by the liver, and sustained accumulation with slow degradation, as represented by the kidney and bone. The liver accumulated a large fraction of the dose in 1 minute. Most of this was degraded or gone by 10 min and nearly all by 30 min. The kidney was a primary target organ in terms of concentrating the hormone. Nearly 50% of the initially accumulated CT, however, remained undegraded 60 min post-injection. The bone, to a lesser extent, concentrated the hormone where 70% remained undegraded 60 min post-injection. The bone accumulated significantly less CT while the kidney and liver accumulated more in 8-month-old rats compared to 24-day-old rats. This suggests that the relative ineffectiveness of CT in older animals as a hypocalcemic agent may be due in part to the inability of the bone to accumulate available hormone.

  10. Expression of thyroglobulin and calcitonin in spontaneous thyroid gland tumors in the Han Wistar rat.

    Science.gov (United States)

    Pilling, Andrew M; Jones, Stewart A; Endersby-Wood, Helen J; McCormack, Nicola A M; Turton, John A

    2007-04-01

    Spontaneous follicular and C-cell tumors of the thyroid gland in the Han Wistar rat were examined using two morphologic procedures. Firstly, in situ hybridization (ISH) was used to localize thyroglobulin (TG) and calcitonin (CT) mRNAs. Secondly, the proteins for these markers were detected using immunohistochemistry (IHC). The aim was to study the morphology of the tumors and to examine the usefulness of TG and CT markers in the differential diagnosis of these lesions. Follicular tumors with cystic, papillary and follicular patterns showed relatively consistent expression of TG mRNA by ISH, thereby confirming the diagnostic value of this technique. However, no staining for TG markers was observed in solid lesions. In general, C-cell tumors comprised well-differentiated cells that continued to express CT mRNA and peptides even after embolic spread and metastasis. Therefore, the performance of either ISH or IHC for CT markers can be used for diagnostic confirmation. Additional features noted in C-cell tumors included the appearance of tumor emboli or metastases in association with small primary lesions (less than 5 average follicular diameters in size) and the presence of eosinophilic (amyloid-like) material showing immunopositivity for CT peptides. Finally, evidence is provided for the sequestration of TG protein by proliferating C-cells.

  11. Comparative assessment of in vitro release kinetics of calcitonin polypeptide from biodegradable microspheres.

    Science.gov (United States)

    Prabhu, Sunil; Sullivan, Jennifer L; Betageri, Guru V

    2002-01-01

    The objective of our study was to compare the in vitro release kinetics of a sustained-release injectable microsphere formulation of the polypeptide drug, calcitonin (CT), to optimize the characteristics of drug release from poly-(lactide-co-glycolide) (PLGA) copolymer biodegradable microspheres. A modified solvent evaporation and double emulsion technique was used to prepare the microspheres. Release kinetic studies were carried out in silanized tubes and dialysis bags, whereby microspheres were suspended and incubated in phosphate buffered saline, sampled at fixed intervals, and analyzed for drug content using a modified Lowry protein assay procedure. An initial burst was observed whereby about 50% of the total dose of the drug was released from the microspheres within 24 hr and 75% within 3 days. This was followed by a period of slow release over a period of 3 weeks in which another 10-15% of drug was released. Drug release from the dialysis bags was more gradual, and 50% CT was released only after 4 days and 75% after 12 days of release. Scanning electron micrographs revealed spherical particles with channel-like structures and a porous surface after being suspended in an aqueous solution for 5 days. Differential scanning calorimetric studies revealed that CT was present as a mix of amorphous and crystalline forms within the microspheres. Overall, these studies demonstrated that sustained release of CT from PLGA microspheres over a 3-week period is feasible and that release of drug from dialysis bags was more predictable than from tubes.

  12. EXPRESSION OF CALCITONIN GENE-RELATED PEPTIDE IN FACIAL NERVE OF HEMIFACIAL SPASM

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    Objective To study the immunoreactivity of Calcitonin gene-related peptide (CGRP) in the facial nerve when Hemifacial Spasm is occurring. Methods The electrophysiological technique was used to explore abnormal muscle response (AMR) which was characteristic of Hemifacial Spasm.The animal models of Hemifacial Spasm in New Zealand white rabbits were established by compressing the main trunk of artificial demyelinated facial nerve with the temporal superficial artery. At 6 weeks after surgery, the facial nerves were taken from the experimental group and control one, the immunohistochemistry for CGRP using polyclonal antibody with ABC kit was performed in the facial nerves; at the same time, the observation for the facial nerves of light and transmission electron microscope was performed. Results The facial nerve demyelinated and the axons retrogressively changed, CGRP immunoreactive positive fibers were significantly detected in experimental groups; whereas this phenomenon was not found in control group. Conclusion CGRP can nutrien the injured facial nerve and plays an important role in the pathogenesis of Hemifacial Spasm.

  13. Calcitonin gene-related peptide in the joint: contributions to pain and inflammation.

    Science.gov (United States)

    Walsh, David A; Mapp, Paul I; Kelly, Sara

    2015-11-01

    Arthritis is the commonest cause of disabling chronic pain, and both osteoarthritis (OA) and rheumatoid arthritis (RA) remain major burdens on both individuals and society. Peripheral release of calcitonin gene-related peptide (CGRP) contributes to the vasodilation of acute neurogenic inflammation. Contributions of CGRP to the pain and inflammation of chronic arthritis, however, are only recently being elucidated. Animal models of arthritis are revealing the molecular and pathophysiological events that accompany and lead to progression of both arthritis and pain. Peripheral actions of CGRP in the joint might contribute to both inflammation and joint afferent sensitization. CGRP and its specific receptors are expressed in joint afferents and up-regulated following arthritis induction. Peripheral CGRP release results in activation of synovial vascular cells, through which acute vasodilatation is followed by endothelial cell proliferation and angiogenesis, key features of chronic inflammation. Local administration of CGRP to the knee also increases mechanosensitivity of joint afferents, mimicking peripheral sensitization seen in arthritic joints. Increased mechanosensitivity in OA knees and pain behaviour can be reduced by peripherally acting CGRP receptor antagonists. Effects of CGRP pathway blockade on arthritic joint afferents, but not in normal joints, suggest contributions to sensitization rather than normal joint nociception. CGRP therefore might make key contributions to the transition from normal to persistent synovitis, and the progression from nociception to sensitization. Targeting CGRP or its receptors within joint tissues to prevent these undesirable transitions during early arthritis, or suppress them in established disease, might prevent persistent inflammation and relieve arthritis pain.

  14. Substance P and Calcitonin Gene-Related Peptide: Key Regulators of Cutaneous Microbiota Homeostasis

    Science.gov (United States)

    N’Diaye, Awa; Gannesen, Andrei; Borrel, Valérie; Maillot, Olivier; Enault, Jeremy; Racine, Pierre-Jean; Plakunov, Vladimir; Chevalier, Sylvie; Lesouhaitier, Olivier; Feuilloley, Marc G. J.

    2017-01-01

    Neurohormones diffuse in sweat and epidermis leading skin bacterial microflora to be largely exposed to these host factors. Bacteria can sense a multitude of neurohormones, but their role in skin homeostasis was only investigated recently. The first study focused on substance P (SP), a neuropeptide produced in abundance by skin nerve terminals. SP is without effect on the growth of Gram-positive (Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis) and Gram-negative (Pseudomonas fluorescens) bacteria. However, SP is stimulating the virulence of Bacillus and Staphylococci. The action of SP is highly specific with a threshold below the nanomolar level. Mechanisms involved in the response to SP are different between bacteria although they are all leading to increased adhesion and/or virulence. The moonlighting protein EfTu was identified as the SP-binding site in B. cereus and Staphylococci. In skin nerve terminals, SP is co-secreted with the calcitonin gene-related peptide (CGRP), which was shown to modulate the virulence of S. epidermidis. This effect is antagonized by SP. Identification of the CGRP sensor, DnaK, allowed understanding this phenomenon as EfTu and DnaK are apparently exported from the bacterium through a common system before acting as SP and CGRP sensors. Many other neuropeptides are expressed in skin, and their potential effects on skin bacteria remain to be investigated. Integration of these host signals by the cutaneous microbiota now appears as a key parameter in skin homeostasis. PMID:28194136

  15. Presence by radioimmunoassay of a calcitonin-like substance in porcine pituitary glands

    Energy Technology Data Exchange (ETDEWEB)

    Catherwood, B.D.; Deftos, L.J.

    1980-06-01

    We studied acidic acetone extracts of whole porcine pituitary glands for the presence of immunoreactive calcitonin (CT) using a porcine CT (pCT) RIA which did not react with other known pituitary hormones. Four preparations of porcine pituitary extract contained immunoreactive CT. Three of these displayed inhibition of binding parallel to that of authentic pCT in the pCT RIA and contained a single peak of immunoreactivity similar to pCT when studied by two different gel filtration chromatography systems. One preparation of porcine pituitary extract showed nonparallelism in RIA dose-dilution experiments and multiple immunoreactive species both similar to and larger than pCT on gel filtration in 6 M guanidine HCl. The effect of the reduction of disulfide bonds, followed by carboxymethylation of sulfhydryl groups, on immunoreactivity and apparent molecular size was similar for the CT-like substance in porcine pituitary extract and for authentic pCT. Preliminary immunohistological studies showed cytoplasmic staining in cells of the porcine adenohypophysis. These results demonstrate that the porcine pituitary gland contains a substance which has some of the immunochemical and biochemical properties of thyroidal pCT.

  16. Calcitonin gene-related peptide regulates type IV hypersensitivity through dendritic cell functions.

    Directory of Open Access Journals (Sweden)

    Norihisa Mikami

    Full Text Available Dendritic cells (DCs play essential roles in both innate and adaptive immune responses. In addition, mutual regulation of the nervous system and immune system is well studied. One of neuropeptides, calcitonin gene-related peptide (CGRP, is a potent regulator in immune responses; in particular, it has anti-inflammatory effects in innate immunity. For instance, a deficiency of the CGRP receptor component RAMP 1 (receptor activity-modifying protein 1 results in higher cytokine production in response to LPS (lipopolysaccharide. On the other hand, how CGRP affects DCs in adaptive immunity is largely unknown. In this study, we show that CGRP suppressed Th1 cell differentiation via inhibition of IL-12 production in DCs using an in vitro co-culture system and an in vivo ovalbumin-induced delayed-type hypersensitivity (DTH model. CGRP also down-regulated the expressions of chemokine receptor CCR2 and its ligands CCL2 and CCL12 in DCs. Intriguingly, the frequency of migrating CCR2(+ DCs in draining lymph nodes of RAMP1-deficient mice was higher after DTH immunization. Moreover, these CCR2(+ DCs highly expressed IL-12 and CD80, resulting in more effective induction of Th1 differentiation compared with CCR2(- DCs. These results indicate that CGRP regulates Th1 type reactions by regulating expression of cytokines, chemokines, and chemokine receptors in DCs.

  17. Bilateral germinoma of the basal ganglia.

    Science.gov (United States)

    Rossi, Andrea; Garrè, Maria Luisa; Ravegnani, Marcello; Nozza, Paolo; Abbruzzese, Arturo; Giangaspero, Felice; Tortori-Donati, Paolo

    2008-01-01

    Germinoma arising in the bilateral basal ganglia is exceedingly rare, with only five cases reported to date. Owing to non-specific clinical findings and the frequent presence of ill-defined abnormalities without a definite tumor mass on neuroimaging, the diagnosis can be difficult. We describe a case in which magnetic resonance spectroscopy (MRS) findings suggested a tumor and supported the decision to perform biopsy of the lesion.

  18. Basal ganglia lesions in children and adults

    Energy Technology Data Exchange (ETDEWEB)

    Bekiesinska-Figatowska, Monika, E-mail: m.figatowska@mp.pl [Department of Diagnostic Imaging, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Mierzewska, Hanna, E-mail: h.mierzewska@gmail.com [Department of Neurology of Children and Adolescents, Institute of Mother and Child, ul. Kasprzaka 17a, 01-211 Warsaw (Poland); Jurkiewicz, Elżbieta, E-mail: e-jurkiewicz@o2.pl [Department of Diagnostic Imaging, Children' s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw (Poland)

    2013-05-15

    The term “basal ganglia” refers to caudate and lentiform nuclei, the latter composed of putamen and globus pallidus, substantia nigra and subthalamic nuclei and these deep gray matter structures belong to the extrapyramidal system. Many diseases may present as basal ganglia abnormalities. Magnetic resonance imaging (MRI) and computed tomography (CT) – to a lesser degree – allow for detection of basal ganglia injury. In many cases, MRI alone does not usually allow to establish diagnosis but together with the knowledge of age and circumstances of onset and clinical course of the disease is a powerful tool of differential diagnosis. The lesions may be unilateral: in Rassmussen encephalitis, diabetes with hemichorea/hemiballism and infarction or – more frequently – bilateral in many pathologic conditions. Restricted diffusion is attributable to infarction, acute hypoxic–ischemic injury, hypoglycemia, Leigh disease, encephalitis and CJD. Contrast enhancement may be seen in cases of infarction and encephalitis. T1-hyperintensity of the lesions is uncommon and may be observed unilaterally in case of hemichorea/hemiballism and bilaterally in acute asphyxia in term newborns, in hypoglycemia, NF1, Fahr disease and manganese intoxication. Decreased signal intensity on GRE/T2*-weighted images and/or SWI indicating iron, calcium or hemosiderin depositions is observed in panthotenate kinase-associated neurodegeneration, Parkinson variant of multiple system atrophy, Fahr disease (and other calcifications) as well as with the advancing age. There are a few papers in the literature reviewing basal ganglia lesions. The authors present a more detailed review with rich iconography from the own archive.

  19. Basal hydraulic conditions of Ice Stream B

    Science.gov (United States)

    Engelhardt, Hermann; Kamb, Barclay

    1993-01-01

    Fifteen boreholes have been drilled to the base of Ice Stream B in the vicinity of UpB Camp. The boreholes are spread over an area of about 500 x 1000 m. Several till cores were retrieved from the bottom of the 1000-m-deep holes. Laboratory tests using a simple shear box revealed a yield strength of basal till of 2 kPa. This agrees well with in-situ measurements using a shear vane. Since the average basal shear stress of Ice Stream B with a surface slope of 0.1 degree is about 20 kPa, the ice stream cannot be supported by till that weak. Additional support for this conclusion comes from the basal water pressure that has been measured in all boreholes as soon as the hot water drill reached bottom. In several boreholes, the water pressure has been continuously monitored; in two of them, over several years. The water pressure varies but stays within 1 bar of flotation where ice overburden pressure and water pressure are equal. The ratio of water and overburden pressure lies between 0.986 and 1.002. This is an extremely high value as compared to other fast-moving ice masses; e.g., Variegated Glacier in surge has a ratio of 0.8, and Columbia Glacier - a fast-moving tidewater glacier - has a ratio of 0.9. It implies that water flow under the glacier occurs in a thin film and not in conduits that would drain away water too rapidly. It also implies that basal sliding must be very effective. Water flow under the glacier was measured in a salt-injection experiment where a salt pulse was released at the bottom of a borehole while 60 m down-glacier, the electrical resistance was measured between two other boreholes. A flow velocity of 7 mm/s was obtained.

  20. 高效液相色谱法测定鲑鱼降钙素混悬型气雾剂的含量%Determination of Salmon Calcitonin in Salmon Calcitonin Suspension Aerosol by HPLC

    Institute of Scientific and Technical Information of China (English)

    吴涵; 陈龙楷; 单紫筠; 潘昕; 吴传斌

    2014-01-01

    Objectiv To establish a method for the content determination of salmon calcitonin in Salmon Calcitonin Suspension Aerosol. Methods The chromatographic column was the Phenomenex Jupiter 300 Å C18 column ( 250 mm × 4. 6 mm, 5μm ) . The mobile phase A was 0. 02 mol/L tetramethyl ammonium hydroxide solution ( pH=2. 5 ) and the mobile phase B was acetonitrile. The samples were determined with binary gradient elution at a flow rate of 1. 0 mL/min and the UV detection wavelength at 220 nm. The column temperature was at 40℃. Results There was a good linear relationship between the peak area and the salmon calcitonin concentra-tion within the range of 0. 8-50 μg/mL, and the regression equation was A=4. 508 7 × 104ρ-7. 394 8 × 103, r=0. 999 7 ( n=7). The average recovery rate was 98. 24%, RSD=1. 18%. The average content of salmon calcitonin in salmon calcitonin suspension Aerosol was 1. 41 mg. Conclusion The HPLC method is accurate, reliable, easy operation and suitable for the content determination of Salmon Calci-tonin Suspension Aerosol.%目的:建立测定鲑鱼降钙素混悬型气雾剂中鲑鱼降钙素含量的高效液相色谱法。方法采用Phenomenex Jupiter C18300Ù色谱柱(250 mm ×4.6 mm,5μm),流动相A(0.02 mol/L四甲基氢氧化铵,pH=2.5)、流动相B(乙腈)进行二元梯度洗脱,流速为1.0 mL/min,紫外检测波长为220 nm,柱温为40℃。结果鲑鱼降钙素质量浓度在0.8~50μg/mL范围内与峰面积成良好线性关系,回归方程为A=4.5087×104ρ-7.3948×103,r=0.9997( n=7),加样回收率为98.24%,RSD为1.18%。测得鲑鱼降钙素混悬型气雾剂中鲑鱼降钙素平均含量为每瓶1.41 mg。结论该法准确、可靠、操作简便,适用于鲑鱼降钙素混悬型气雾剂的含量测定。

  1. Salmon calcitonin combined with ossification in three alcohol treatment of renal osteopathy%鲑鱼降钙素结合骨化三醇治疗肾性骨病疗效观察

    Institute of Scientific and Technical Information of China (English)

    杨静; 张江淮; 吴永贵; 胡淑荣

    2013-01-01

    Objective:To observe the effects of salmon calcitonin combined ossification in three alcohol for treatment of renal osteodystrophy (renal osteopathy) effect. Methods:66 cases of patients with renal osteodystrophy were randomly divided into treatment group and control group, were treated with the basis of disease treatment, the treatment group added with salmon calcitonin (3 times 20 u, subcutaneous injection, once a week (with conventional hemodialysis), at the same time plus oral ossification in three alcohol treatment (0.25-1.0ug/D);control group with salmon calcitonin, parathyroid hormone in blood were detected before treatment and 3, 6, and 12 months (PTH), serum calcium, serum phosphorus level and lumbar pain, and the record level (visual analogue scale, VAS) and adverse reaction. Results:in the control group before treatment, serum calcium, serum phosphorus and PTH were 2.10 ± 0.28, 2.82 ± 0.34, 868.50 ± 125.57, after treatment were 2.34 ± 0.23, 2.23 ± 0.23 and 723.39 ± 117.73;the treatment group before treatment of parathyroid hormone (PTH), serum calcium, serum phosphorus level of 2.15 ± 0.40, 2.78 ± 0.45 、891.45 ± 124.73, after treatment were 2.78 ± 0.46, 2.12 ± 0.21, 610.57 ± 124.12, before and after the treatment, the difference was statistical y significant (P<0.05), the treatment group improved more obviously (P<0.05). Conclusion:the application of salmon calcitonin and combined with ossification in three alcohol can effectively reduce MHD in patients with bone loss in patients with renal osteodystrophy, decrease the level of PTH, improve the clinical symptomsand no obvious adverse reaction. It is worthy of clinical application.%目的:观察鲑鱼降钙素联合骨化三醇治疗肾性骨病(renal osteopathy)的疗效。方法:对66例肾性骨病患者随机分为治疗组和对照组,均予以治疗基础疾病,治疗组加用鲑鱼降钙素(20 u,皮下注射,每周3次(常规血液透析时使用),同时

  2. Genetics Home Reference: familial idiopathic basal ganglia calcification

    Science.gov (United States)

    ... idiopathic basal ganglia calcification ( FIBGC , formerly known as Fahr disease) is a condition characterized by abnormal deposits of ... on chromosome 14q for idiopathic basal ganglia calcification (Fahr disease). Am J Hum Genet. 1999 Sep;65(3): ...

  3. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway.

    Science.gov (United States)

    Wulf-Johansson, H; Amrutkar, D V; Hay-Schmidt, A; Poulsen, A N; Klaerke, D A; Olesen, J; Jansen-Olesen, I

    2010-06-02

    Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS11021 on CGRP release from isolated TG and TNC was investigated. By RT-PCR, BK(Ca) channel mRNA was detected in the TG and the TNC. A significant difference in BK(Ca) channel mRNA transcript levels were found using qPCR between the TNC as compared to the TG. The BK(Ca) channel protein was more expressed in the TNC as compared to the TG shown by western blotting. Immunohistochemistry identified BK(Ca) channels in the nerve cell bodies of the TG and the TNC. The beta2- and beta4-subunit proteins were found in the TG and the TNC. They were both more expressed in the TNC as compared to TG shown by western blotting. In isolated TNC, the BK(Ca) channel blocker iberiotoxin induced a concentration-dependent release of CGRP that was attenuated by the BK(Ca) channel opener NS11021. No effect on basal CGRP release was found by NS11021 in isolated TG or TNC or by iberiotoxin in TG. In conclusion, we found both BK(Ca) channel mRNA and protein expression in the TG and the TNC. The BK(Ca) channel protein and the modulatory beta2- and beta4-subunt proteins were more expressed in the TNC than in the TG. Iberiotoxin induced an increase in CGRP release from the TNC that was attenuated by NS11021. Thus, BK(Ca) channels might have a role in trigeminovascular pain transmission.

  4. Integrated profiling of basal and luminal breast cancers.

    NARCIS (Netherlands)

    Adelaide, J.; Finetti, P.; Bekhouche, I.; Repellini, L.; Geneix, J.; Sircoulomb, F.; Charafe-Jauffret, E.; Cervera, N.; Desplans, J.; Parzy, D.; Schoenmakers, E.F.P.M.; Viens, P.; Jacquemier, J.; Birnbaum, D.; Bertucci, F.; Chaffanet, M.

    2007-01-01

    Basal and luminal are two molecular subtypes of breast cancer with opposite histoclinical features. We report a combined, high-resolution analysis of genome copy number and gene expression in primary basal and luminal breast cancers. First, we identified and compared genomic alterations in 45 basal

  5. Availability of the basal planes of graphene oxide determines whether it is antibacterial.

    Science.gov (United States)

    Hui, Liwei; Piao, Ji-Gang; Auletta, Jeffrey; Hu, Kan; Zhu, Yanwu; Meyer, Tara; Liu, Haitao; Yang, Lihua

    2014-08-13

    There are significant controversies on the antibacterial properties of graphene oxide (GO): GO was reported to be bactericidal in saline, whereas its activity in nutrient broth was controversial. To unveil the mechanisms underlying these contradictions, we performed antibacterial assays under comparable conditions. In saline, bare GO sheets were intrinsically bactericidal, yielding a bacterial survival percentage of planes. Using bovine serum albumin and tryptophan as well-defined model adsorbates, we found that noncovalent adsorption on GO basal planes may account for the deactivation of GO's bactericidal activity. Moreover, this deactivation mechanism was shown to be extrapolatable to GO's cytotoxicity against mammalian cells. Taken together, our observations suggest that bare GO intrinsically kills both bacteria and mammalian cells and noncovalent adsorption on its basal planes may be a global deactivation mechanism for GO's cytotoxicity.

  6. Adenoid basal cell carcinoma and its mimics

    Directory of Open Access Journals (Sweden)

    Sujata Jetley

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common malignant tumor of skin. The most common site (80% is head and neck. BCC exhibits a varied morphology such as adenoid, keratotic, sebaceous, basosquamous, apocrine, eccrine or fibroepithelial. Tumors with a similar histopathological picture are cutaneous adenoid cystic carcinoma and primary cutaneous cribriform apocrine carcinoma. Immunohistochemistry, along with clinical findings, acts as an adjunct in reaching an accurate diagnosis. Here, we present an interesting case of adenoid BCC in a 55-year-old man.

  7. Nonsurgical Treatment Options for Basal Cell Carcinoma

    Directory of Open Access Journals (Sweden)

    Mary H. Lien

    2011-01-01

    Full Text Available Basal cell carcinoma (BCC remains the most common form of nonmelanoma skin cancer (NMSC in Caucasians, with perhaps as many as 2 million new cases expected to occur in the United States in 2010. Many treatment options, including surgical interventions and nonsurgical alternatives, have been utilized to treat BCC. In this paper, two non-surgical options, imiquimod therapy and photodynamic therapy (PDT, will be discussed. Both modalities have demonstrated acceptable disease control rates, cosmetically superior outcomes, and short-term cost-effectiveness. Further studies evaluating long-term cure rates and long-term cost effectiveness of imiquimod therapy and PDT are needed.

  8. Mössbauer spectroscopy of Basal Ganglia

    Energy Technology Data Exchange (ETDEWEB)

    Miglierini, Marcel, E-mail: marcel.miglierini@stuba.sk [Institute of Nuclear and Physical Engineering, Faculty of Electrical Engineering and Information Technology, Slovak University of Technology, Ilkovičova 3, 812 19 Bratislava, Slovakia and Regional Centre of Advanced Technologies and Materials (Czech Republic); Lančok, Adriana [Institute of Inorganic Chemistry AS CR, v. v. i., 250 68 Husinec-Řež 1001 (Czech Republic); Kopáni, Martin [Institute of Medical Physics, Biophysics, Informatics and Telemedicine, Faculty of Medicine, Comenius University, Sasinkova 2, 811 08 Bratislava (Slovakia); Boča, Roman [Department of Chemistry, Faculty of Natural Sciences, University of SS. Cyril and Methodius, 917 01 Trnava (Slovakia)

    2014-10-27

    Chemical states, structural arrangement, and magnetic features of iron deposits in biological tissue of Basal Ganglia are characterized. The methods of SQUID magnetometry and electron microscopy are employed. {sup 57}Fe Mössbauer spectroscopy is used as a principal method of investigation. Though electron microscopy has unveiled robust crystals (1-3 μm in size) of iron oxides, they are not manifested in the corresponding {sup 57}Fe Mössbauer spectra. The latter were acquired at 300 K and 4.2 K and resemble ferritin-like behavior.

  9. Archaefructaceae, a new basal angiosperm family.

    Science.gov (United States)

    Sun, Ge; Ji, Qiang; Dilcher, David L; Zheng, Shaolin; Nixon, Kevin C; Wang, Xinfu

    2002-05-03

    Archaefructaceae is proposed as a new basal angiosperm family of herbaceous aquatic plants. This family consists of the fossils Archaefructus liaoningensis and A. sinensis sp. nov. Complete plants from roots to fertile shoots are known. Their age is a minimum of 124.6 million years from the Yixian Formation, Liaoning, China. They are a sister clade to all angiosperms when their characters are included in a combined three-gene molecular and morphological analysis. Their reproductive axes lack petals and sepals and bear stamens in pairs below conduplicate carpels.

  10. Uridine branch acceptor is a cis-acting element involved in regulation of the alternative processing of calcitonin/CGRP-l pre-mRNA.

    OpenAIRE

    Adema, G. J.; van Hulst, K L; Baas, P.D.

    1990-01-01

    The human calcitonin/CGRP-I (CALC-I) gene contains 6 exons and encodes two polypeptide precursors. In thyroid C-cells, calcitonin (CT) mRNA is produced by splicing of exons 1-2-3 to exon 4 (CT-encoding) and polyadenylation at exon 4. CGRP-I mRNA is produced in particular neural cells by splicing of exons 1-2-3 to exon 5 (CGRP-I-encoding) and the polyadenylated exon 6. We previously reported that model precursor RNAs containing the exon 3 to exon 5 region of the CALC-I gene are processed predo...

  11. Synthesis, characterization and evaluation of bone targeting salmon calcitonin analogs in normal and osteoporotic rats.

    Science.gov (United States)

    Bhandari, Krishna Hari; Newa, Madhuri; Chapman, Jillian; Doschak, Michael R

    2012-02-28

    In order to assess the therapeutic efficacy of an antiresorptive drug with imparted bone targeting potential using bisphosphonate (BP) conjugation and an improved pharmacokinetic profile using PEGylation, we synthesized, characterized and evaluated in vivo efficacy of bone-targeting PEGylated salmon calcitonin (sCT) analog (sCT-PEG-BP). sCT-PEG-BP was compared with non-PEGylated bone targeting sCT analog (sCT-BP) and unmodified, commercially available sCT. sCT-PEG-BP conjugates were characterized by matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) analysis. The effect of PEG-BP or BP upon sCT secondary structure was examined by Circular Dichroism and sCT-PEG-BP was evaluated for in vitro bone mineral Hydroxyapatite (HA) binding ability and calcium salts specificity using a binding assay for bone HA and several calcium salts. Anti-calcitonin antibody binding ability of these analogs was determined using enzyme-linked immunosorbent assay (ELISA), by reacting bone targeting sCT analogs with calcium phosphate coated Osteologic® plates and detecting the bound sCT using anti-sCT antibody. Potential cytotoxicity of these compounds was evaluated in monocytic RAW 264.7 cells, and sCT bioactivity was evaluated using an in vitro intracellular cAMP stimulation assay in human T47D breast cancer cells. Finally, in vivo efficacy of each compound was evaluated by determining the plasma levels of calcium after s.c. administration in normal rats, and in a rat model of Osteoporosis, secondary to ovariectomy (OVX). In vivo micro-computed tomography (micro-CT) was used to temporally map and quantify alterations in bone volume and bone mineral density (BMD) in the same animals at 1, 4, 8 and 12 weeks after OVX surgery. Sixteen 6 week old virgin female rats underwent OVX surgery followed by the daily s.c. injection of 2.5IU/kg/day sCT or equivalent analogs, and compared to four sham-operated, placebo treated control rats. Our results showed the chemical coupling of

  12. Differential distribution of calcitonin gene-related peptide and its receptor components in the human trigeminal ganglion

    DEFF Research Database (Denmark)

    Eftekhari, S; Salvatore, C A; Calamari, A;

    2010-01-01

    system and hence the potential antagonist sites of action remain unknown. Therefore we designed a study to evaluate the localization of CGRP and its receptor components calcitonin receptor-like receptor (CLR) and receptor activity modifying protein (RAMP) 1 in the human trigeminal ganglion using...... immunohistochemistry and compare with that of rat. Antibodies against purified CLR and RAMP1 proteins were produced and characterized for this study. Trigeminal ganglia were obtained at autopsy from adult subjects and sections from rat trigeminal ganglia were used to compare the immunostaining pattern. The number...

  13. Isolation and molecular characterization of porcine calcitonin gene-related peptide (CGRP) and its endocrine effects in the porcine pancreas

    DEFF Research Database (Denmark)

    Rasmussen, T N; Bersani, M; Schmidt, P;

    1998-01-01

    The aim of this study was to investigate the possible role of porcine calcitonin gene-related peptide (CGRP) in the regulation of the endocrine porcine pancreas. Initially, we isolated and purified CGRP from extracts of porcine adrenal glands and pancreases. A single molecular form of the peptide...... was found in the two tissues. The adrenal peptide was sequenced and found to differ from human alpha-CGRP at six positions and from human beta-CGRP at three positions. By immunohistochemistry, CGRP was found in nerve fibers in the pancreatic ganglia. A synthetic replica of the porcine peptide was infused...

  14. Effectiveness of combined salmon calcitonin and aspirin therapy for osteoporosis in ovariectomized rats.

    Science.gov (United States)

    Wei, Jinsong; Wang, Jian; Gong, Yan; Zeng, Rong

    2015-08-01

    The objective of the present study was to assess the effectiveness of combined salmon calcitonin (sCT) and aspirin [acetylsalicylic acid (ASA)] treatment in an ovariectomized (OVX) rat model of postmenopausal osteoporosis. Following 12 weeks of treatment, therapeutic efficacy was assessed by evaluating changes in the biochemical and biophysical properties of bone (n=8 rats per group). Serological markers of bone metabolism were measured by ELISA; bone mineral densities (BMD) by dual energy X-ray absorptiometry; bone biomechanics of the femur and lumbar vertebrae by three-point stress test; trabecular bone morphology of lumbar vertebrae by hematoxylin and eosin staining; messenger RNA expression levels of osteoprotegerin (OPG) and receptor activator of nuclear factor κB ligand (RANKL) in bone marrow cells by reverse transcription-quantitative polymerase chain reaction and OPG and RANKL protein expression levels in the proximal tibia were analyzed by immunohistochemistry. Compared with treatment by sCT or ASA alone, combined treatment (sCT+ASA) increased BMD, improved femur bone strength, normalized trabecular network architecture and morphology, and increased mRNA and protein expression of OPG, while reducing the expression of RANKL. Collectively, these results demonstrated that combined treatment (sCT+ASA) of osteoporotic symptoms in OVX rats was more effective than treatment with sCT or ASA alone. Furthermore, these two drugs appeared to alter the expression of two distinct factors in the OPG/RANKL/RANK system, suggesting that their effects may be synergistic. Since sCT and ASA are currently approved for use in humans, the results of the present study suggest that the safety and efficacy of sCT+ASA combined therapy for post-menopausal osteoporosis should be assessed in clinical trials.

  15. Evaluation of HPβCD-PEG microparticles for salmon calcitonin administration via pulmonary delivery.

    Science.gov (United States)

    Tewes, Frederic; Gobbo, Oliviero L; Amaro, Maria I; Tajber, Lidia; Corrigan, Owen I; Ehrhardt, Carsten; Healy, Anne Marie

    2011-10-03

    For therapeutic peptides, the lung represents an attractive, noninvasive route into the bloodstream. To achieve optimal bioavailability and control their fast rate of absorption, peptides can be protected by coprocessing with polymers such as polyethylene glycol (PEG). Here, we formulated and characterized salmon calcitonin (sCT)-loaded microparticles using linear or branched PEG (L-PEG or B-PEG) and hydroxypropyl-beta-cyclodextrin (HPβCD) for pulmonary administration. Mixtures of sCT, L-PEG or B-PEG and HPβCD were co-spray dried. Based on the particle properties, the best PEG:HPβCD ratio was 1:1 w:w for both PEGs. In the sCT-loaded particles, the L-PEG was more crystalline than B-PEG. Thus, L-PEG-based particles had lower surface free energy and better aerodynamic behavior than B-PEG-based particles. However, B-PEG-based particles provided better protection against chemical degradation of sCT. A decrease in sCT permeability, measured across Calu-3 bronchial epithelial monolayers, occurred when the PEG and HPβCD concentrations were both 1.6 wt %. This was attributed to an increase in buffer viscosity, caused by the two excipients. sCT pharmacokinetic profiles in Wistar rats were evaluated using a 2-compartment model after iv injection or lung insufflation. The maximal sCT plasma concentration was reached within 3 min following nebulization of sCT solution. L-PEG and B-PEG-based microparticles were able to increase T(max) to 20 ± 1 min and 18 ± 8 min, respectively. Furthermore, sCT absolute bioavailability after L-PEG-based microparticle aerosolization at 100 μg/kg was 2.3 times greater than for the nebulized sCT solution.

  16. Parathyroid hormone and calcitonin interactions in bone: Irradiation-induced inhibition of escape in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Krieger, N.S.; Tashjian, A.H. Jr.; Feldman, R.S.

    1982-01-01

    Calcitonin (CT) inhibits hormonally stimulated bone resorption only transiently in vitro. This phenomenon has been termed ''escape,'' but the mechanism for the effect is not understood. One possible explanation is that bone cell differentiation and recruitment of specific precursor cells, in response to stimulators of resorption, lead to the appearance of osteoclasts that are unresponsive to CT. To test this hypothesis, cell proliferation in neonatal mouse calvaria in organ culture was inhibited by irradiation from a cobalt-60 source. At a dose of 6000 R, (/sup 3/H)thymidine incorporation into intact calvaria was inhibited approximately 90%. Irradiation had no effect on the resorptive response to 0.1 U/ml parathyroid hormone (PTH). However, irradiation induced a dose-dependent inhibition of the escape response which was maximal at 6000 R. A dose of 6000 R did not affect the binding of /sup 125/I-salmon CT to calvaria and decreased PTH stimulation of cyclic AMP release from bone without affecting the cyclic AMP response to CT. Although irradiation caused a dose-dependent inhibition of DNA synthesis, the dose-response curves for that effect and inhibition of escape were not superimposable. A morphologic study of hormonally treated calvaria demonstrated that irradiation prevented the early increase in number of osteoclasts in PTH-treated calvaria that had been observed previously in unirradiated bones. Autoradiography showed that irradiation also prevented the PTH-stimulated recruitment of newly divided mononuclear cell precursors into osteoclasts. This may be correlated with the effect of irradiation to prevent the loss of responsiveness to CT in the presence of PTH.

  17. Oral salmon calcitonin improves fasting and postprandial glycemic control in lean healthy rats.

    Science.gov (United States)

    Feigh, M; Nielsen, R H; Hansen, C; Henriksen, K; Christiansen, C; Karsdal, M A

    2012-02-01

    A novel oral form of salmon calcitonin (sCT) was recently demonstrated to improve both fasting and postprandial glycemic control and induce weight loss in diet-induced obese and insulin-resistant rats. To further explore the glucoregulatory efficacy of oral sCT, irrespective of obesity and metabolic dysfunction, the present study investigated the effect of chronic oral sCT treatment on fasting and postprandial glycemic control in male lean healthy rats. 20 male rats were divided equally into a control group receiving oral vehicle or an oral sCT (2 mg/kg) group. All rats were treated twice daily for 5 weeks. Body weight and food intake were monitored during the study period and fasting blood glucose, plasma insulin and insulin sensitivity were determined and an oral glucose tolerance test (OGTT) performed at study end. Compared with the vehicle group, rats receiving oral sCT had improved fasting glucose homeostasis and insulin resistance, as measured by homeostatic model assessment of insulin resistance index (HOMA-IR), with no change in body weight or fasting plasma insulin. In addition, the rats receiving oral sCT had markedly reduced glycemia and insulinemia during OGTT. This is the first report showing that chronic oral sCT treatment exerts a glucoregulatory action in lean healthy rats, irrespective of influencing body weight. Importantly, oral sCT seems to exert a dual treatment effect by improving fasting and postprandial glycemic control and insulin sensitivity. This and previous studies suggest oral sCT is a promising agent for the treatment of obesity-related insulin resistance and type 2 diabetes.

  18. Preparation and characterization of salmon calcitonin-sodium triphosphate ionic complex for oral delivery.

    Science.gov (United States)

    Lee, Hea Eun; Lee, Min Jung; Park, Cho Rong; Kim, A Young; Chun, Kyung Hwa; Hwang, Hee Jin; Oh, Dong Ho; Jeon, Sang Ok; Kang, Jae Seon; Jung, Tae Sung; Choi, Guang Jin; Lee, Sangkil

    2010-04-19

    Even though salmon calcitonin (sCT) has been known as a potent hypocalcemic agent, only injection or nasal spray products are available on the market. In order to develop oral delivery system of the agent, a novel sCT-sodium tripolyphosphate (STPP) ionic complex was fabricated and also characterized. For the optimization of the ionic complexation, the effect of incubation time and molar ratio between sCT and STPP was evaluated. Particle size of the ionic complex in aqueous media, SEM images, DSC, FT-IR, in vitro release test, stability within the simulated intestinal fluid, and hypocalcemic effect were evaluated. The optimal molar complexation ratio of sCT to STPP was ranged from 1:5 to 1:10 and the complexation efficiency was about 95%. The SEM image has shown that the freeze dried ionic complex has rough morphology in their surface and the particle size in PBS (pH 7.4) was about 220nm. The DSC and FT-IR results provided evidences for ionic interaction between -NH(2) groups and -P horizontal lineO groups of sCT and STPP, respectively. The sCT ionic complex has shown sustained sCT releasing characteristics for 3weeks. The sCT-STPP ionic complex was protective to enzymatic attack and in vivo animal data revealed that the present ionic complex would show continuous hypocalcemic effect. Conclusively, the present sCT-STPP ionic complex formulation thought to be a novel oral delivery candidate for the treatment of osteoporosis.

  19. Improved intestinal delivery of salmon calcitonin by water-in-oil microemulsions.

    Science.gov (United States)

    Fan, Yating; Li, Xinru; Zhou, Yanxia; Fan, Chao; Wang, Xiaoning; Huang, Yanqing; Liu, Yan

    2011-09-15

    Therapeutic peptides are highly potent and specific in their functions, but difficulties in their oral administration require parallel development of viable delivery systems to improve their oral bioavailability. The objective of this study was to explore the feasibility of water-in-oil (w/o) microemulsions for improving the absorption of intraduodenally administered salmon calcitonin (sCT). The w/o microemulsions were prepared from medium chain triglyceride, Tween 80 and Span 80 or soybean phosphatidylcholine, propylene glycol and phosphate saline, and characterized by particle size and in vitro physical stability under dilution with different physiologically relevant diluents. The effects of addition of polymers such as hydroxypropylmethylcellulose and Carbomer into aqueous phase on the properties of microemulsions were assessed. sCT was efficiently encapsulated into microemulsions with nanoscaled diameter ranged from about 6 to 134nm. As expected from the non-ionic nature of the investigated microemulsions, the physical stability, evaluated by visual inspection, the particle size and leakage percent under dilution, was found to be unaffected by pH and/or ionic strength of diluents and it was opposite for the microemulsions with ionic components. In addition, the dilution extent had a pronounced effect on the physical stability of the diluted microemulsions. The effect of polymers added into aqueous phase of the microemulsions on the absorption of the drug entrapped in microemulsions with different components was investigated. The optimized microemulsions were shown to generate substantial enhancement (up to 4-fold) of relative pharmacological activity of sCT with regard to the control solution of the drug. This indicated that the w/o microemulsions could offer the potential to significantly improve intestinal absorption of sCT.

  20. Characterisation of salmon calcitonin in spray-dried powder for inhalation. Effect of chitosan.

    Science.gov (United States)

    Yang, M; Velaga, S; Yamamoto, H; Takeuchi, H; Kawashima, Y; Hovgaard, L; van de Weert, M; Frokjaer, S

    2007-03-01

    Salmon calcitonin (sCT) powders suitable for inhalation, containing chitosan and mannitol as absorption enhancer and protection agent, respectively, were prepared using a spray-drying process. The effect of chitosan on physicochemical stability of sCT in the dry powder was investigated by different analytical techniques. High-performance liquid chromatography (HPLC) analysis indicated that sCT was chemically stable upon spray-drying. With the proportion of chitosan in spray-drying formulation being increased, dissolution of sCT from the dry powders was decreased both in phosphate buffer and acetate buffer. The thioflavine T fluorescence assay showed that no fibrils were present in the spray-dried powder. However, sCT partly fibrillated in the phosphate buffer, but not in acetate buffer. Fourier transform infrared (FTIR) spectra showed that the secondary structure of sCT was slightly changed in the dry powder, yet no aggregate signal was observed. Circular dichroism analysis indicated that the structure of sCT in an aqueous formulation was slightly altered by addition of chitosan. Nevertheless, recovery of sCT was not influenced by chitosan in the aqueous formulation as indicated by HPLC analysis. This study suggested that sCT, in absence of any additives, was stable during the spray-drying process under certain conditions. Addition of chitosan affects recovery of sCT from spray-dried powders, which may be due to formation of a partially irreversible complex between the protein and chitosan during the spray-drying process.

  1. Identification and biological activity of ovine and caprine calcitonin receptor-stimulating peptides 1 and 2.

    Science.gov (United States)

    Charles, Christopher J; Katafuchi, Takeshi; Yandle, Timothy G; Minamino, Naoto

    2008-08-01

    We have recently reported the isolation of three new members of the calcitonin (CT) gene-related peptide family of peptides, the CT receptor (CT-R)-stimulating peptides (CRSPs). We now report the sequencing and characterization of ovine/caprine CRSP-1 and caprine CRSP-2. Mature ovine and caprine CRSP-1 are identical and have strong structural homology to CRSP-1s identified to date from other species. As with other CRSP-1s, ovine/caprine CRSP-1 binds to and activates the CT-R but not the CT-like receptor (CL-R) in combination with the receptor activity-modifying proteins (RAMPs). By contrast, caprine CRSP-2 does not activate any of these receptor-RAMP complexes. Intravenous infusions of ovine CRSP-1 to normal conscious sheep induced dose-dependent reduction in plasma total Ca levels (P=0.02) and corrected Ca levels (P=0.017) associated with increases in plasma cAMP (P=0.002). CRSP-1 reduced both plasma amino-terminal pro-C-type natriuretic peptide levels (P=0.006) and plasma renin activity (P=0.028). There were no significant effects observed on hemodynamic or renal indices measured. In conclusion, we have sequenced ovine/caprine CRSP-1 and caprine CRSP-2 precursors. This newly identified CRSP-1 has been shown to share the structural and biological features of CRSP-1s known to date. In vivo studies confirm that ovine CRSP-1 reduces plasma Ca levels in sheep, presumably via a cAMP-mediated mechanism. By contrast, caprine CRSP-2 did not stimulate any combination of CT-R, CL-R, and RAMPs. Accession numbers of cDNA determined in this study are caprine CRSP-1, AB364646; caprine CRSP-2, AB364647; and ovine CRSP-1, AB364648.

  2. Basal cell nevus syndrome or Gorlin syndrome.

    Science.gov (United States)

    Thalakoti, Srikanth; Geller, Thomas

    2015-01-01

    Basal cell nevus syndrome (BCNS) or Gorlin syndrome is a rare neurocutaneous syndrome sometimes known as the fifth phacomatosis, inherited in autosomal dominant fashion with complete penetrance and variable expressivity. Gorlin syndrome is characterized by development of multiple basal cell carcinomas (BCCs), jaw cysts, palmar or plantar pits, calcification of falx cerebri, various developmental skeletal abnormalities such as bifid rib, hemi- or bifid vertebra and predisposition to the development of various tumors. BCNS is caused by a mutation in the PTCH1 gene localized to 9q22.3. Its estimated prevalence varies between 1/55600 and 1/256000 with an equal male to female ratio. The medulloblastoma variant seen in Gorlin syndrome patients is of the desmoplastic type, characteristically presenting during the first 3 years of life. Therefore, children with desmoplastic medulloblastoma should be carefully screened for other features of BCNS. Radiation therapy for desmoplastic medulloblastoma should be avoided in BCNS patients as it may induce development of invasive BCCs and other tumors in the skin area exposed to radiation. This syndrome is a multisystem disorder so involvement of multiple specialists with a multimodal approach to detect and treat various manifestations at early stages will reduce the long-term sequelae and severity of the condition. Life expectancy is not significantly altered but morbidity from complications and cosmetic scarring can be substantial.

  3. Design and evaluation of poly(DL-lactic-co-glycolic acid) nanocomposite particles containing salmon calcitonin for inhalation.

    Science.gov (United States)

    Yang, Mingshi; Yamamoto, Hiromitsu; Kurashima, Homare; Takeuchi, Hirofumi; Yokoyama, Toyokazu; Tsujimoto, Hiroyuki; Kawashima, Yoshiaki

    2012-08-15

    Salmon calcitonin, for the treatment of calcium homeostasis and bone remodeling, was used as a model peptide drug and adsorbed on the surface of biodegradable polymeric poly(dl-lactic-co-glycolic acid) (PLGA) nanospheres. Subsequently, the nanospheres were treated using lyophilizer and loaded onto inhalable carrier using Mechanofusion to obtain nanocomposite particles suitable for inhalation. The physicochemical properties and in vitro inhalation properties of the nanocomposite particles were investigated. The pulmonary distribution and pharmacological effect were also evaluated in male Wistar rats. The results showed that the drug loading efficiency of salmon calcitonin on PLGA nanospheres were exceeding 96% (w/w). Inhalation efficiency of the lyophilized PLGA nanospheres was largely improved after they were loaded on the surface of inhalable carrier. Over 50% (w/w) of the lyophilized PLGA nanospheres could be deposited in the alveoli section after intratracheal administration to male Wistar rats, while a rapid elimination rate of the lyophilized nanospheres from the lung was found in pulmonary distribution study. The in vivo pharmacological study showed that the nanocomposite particles exhibited superior hypocalcemic action over salmon calcitonion solution and the lyophilized nanospheres. It suggested that the Mechanofusion(TM) technique can impart improved inhalation properties to the lyophilized nanospheres for pulmonary delivery of therapeutic peptide drugs.

  4. Role of calcitonin gene-related peptide in cerebral vasospasm, and as a therapeutic approach to subarachnoid haemorrhage

    Directory of Open Access Journals (Sweden)

    Stelios eKokkoris

    2012-11-01

    Full Text Available Calcitonin gene-related peptide (CGRP is one of the most potent microvascular vasodilators identified to date. Vascular relaxation and vasodilation is mediated via activation of the CGRP receptor. This atypical receptor is made up of a G-protein-coupled receptor called calcitonin receptor-like receptor (CLR, a single transmembrane protein called receptor activity-modifying protein (RAMP, and an additional protein that is required for Gas coupling, known as receptor component protein (RCP. Several mechanisms involved in CGRP mediated relaxation have been identified. These include nitric oxide (NO-dependent endothelium-dependent mechanisms or cAMP-mediated endothelium-independent pathways; the latter being more common. Subarachnoid haemorrhage (SAH is associated with cerebral vasoconstriction that occurs several days after the haemorrhage and is often fatal. The vasospasm occurs in 30–40% of patients and is the major cause of death from this condition. The vasoconstriction is associated with a decrease in CGRP levels in nerves and an increase in CGRP levels in draining blood, suggesting that CGRP is released from nerves to oppose the vasoconstriction. This evidence has led to the concept that exogenous CGRP may be beneficial in a condition that has proven hard to treat. The present article reviews: a the pathophysiology of delayed ischaemic neurologic deficit after SAH b the basics of the CGRP receptor structure, signal transduction and vasodilatation mechanisms and c the studies that have been conducted so far using CGRP in both animals and humans with SAH.

  5. Basal Cell Nevus Syndrome. A Case Presentation

    Directory of Open Access Journals (Sweden)

    Ángel Luis Cruz Leiva

    2007-12-01

    Full Text Available Basal Cell Nevus Syndrome is an infrequent entity of very low incidence according to reports in medical literature. It is characterized by considerable groups of alterations which are presented in the organism in a variable way, and with localized lesions in the maxillofacial area. A 61 year-old white male patient who lives in the urban area of Cienfuegos city is presented. He has family references of numerous physical deformities since he was born such as mental retardation, presence of moles since the first decade of his life and augmentation of the mandibular body volume. The diagnosis was keratocysts based on the clinical and radiological examinations as well as histopathological studies.

  6. Effects of loratadine and cetirizine on serum levels of neuropeptides in patients with chronic urticaria.

    Science.gov (United States)

    Başak, Pinar Y; Vural, Huseyin; Kazanoglu, Oya O; Erturan, Ijlal; Buyukbayram, Halil I

    2014-12-01

    H1-receptor inhibiting drugs, namely loratadine and cetirizine, were frequently used in treatment of chronic urticaria. Urticarial weal and flare reactions, a neurogenic reflex due to neuropeptides, were reported to be more effectively inhibited by cetirizine than loratadine. The aim of this study was to determine and compare the effects of systemic loratadine and cetirizine treatments on serum levels of selected neuropeptides in chronic urticaria. Treatment groups of either systemic loratadine or cetirizine (10 mg/d), consisting of 16 and 22 patients, respectively, were included. Serum levels of stem cell factor (SCF), neuropeptide Y (NPY), calcitonin gene-related peptide (CGRP), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), and substance P (SP) were detected before and after one week of treatment with antihistamines. Serum NPY and VIP levels were significantly decreased when compared before and after treatment with antihistamines (P neuropeptides. Systemic loratadine and cetirizine treatments in patients with chronic urticaria precisely caused variations in serum levels of neuropeptides. The predominant effect of cetirizine compared to loratadine on reducing serum SCF levels might be explained with anti-inflammatory properties of cetirizine.

  7. Basal body temperature recordings in spontaneous abortion.

    Science.gov (United States)

    Cohen, J; Iffy, L; Keyser, H H

    1976-01-01

    Basal body temperature (BBT) charts taken during the cycle of conception in cases that resulted in spontaneous abortion appear to provide the best available information concerning events associated with time of fertilization in doomed gestations. This study is based on a series of 227 patients who had early spontaneous abortion occurring between January 1967 and December 1974. A diagnosis of pregnancy initiated regular assays of urinary estrogen and pregnanediol excretion. Patients were instructed to report any bleeding episode which might occur, and to preserve all tissues that might be expelled. A total of 11 basal body temperature charts were obtained from patients who had subsequent early spontaneous abortion. Chromosome studies and histologic investigations were conducted. Another group of 11 consecutive BBT records were obtained from patients who had normal deliveries. The study shows that women with normal cycles experience a midcycle temperature rise requiring 1 to 3 days. In subsequent patients, this time limit was exceeded in 7 out of 11 cases of early abortion, and in 4 of 11 fertilization that resulted in an apparently normal gestation and infant. As temperature rise resulted from vigorous progesterone secretion by the corpus luteum, subnormal levels indicate inadequate steroidogenesis in the early luteal phase, and falling estrogen and progesterone levels predicted fetal demise in all cases. These findings are useful in the management of early pregnancy that follows repeated spontaneous first trimester abortions or a prolonged period of infertility. They also confirm experimental and clinical evidence regarding the role of ovulation defects in the occurrence of various types of reproductive wastage, including early abortion, anatomic and chromosome defects of the embryo and others. Prospective studies of cycles of conception through BBT recordings/hormone assays may shed light in the understanding of defects of human reproduction.

  8. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  9. Early stages of salmon calcitonin aggregation: effect induced by ageing and oxidation processes in water and in the presence of model membranes.

    Science.gov (United States)

    Gaudiano, Maria Cristina; Colone, Marisa; Bombelli, Cecilia; Chistolini, Pietro; Valvo, Luisa; Diociaiuti, Marco

    2005-06-30

    The natural ageing- and hydrogen peroxide-induced aggregation of salmon calcitonin were studied in water and in the presence of dipalmitoylphosphatidylcholine (DPPC) liposomes. The early stages of the aggregation process at low protein concentration were investigated by means of Circular Dichroism spectroscopy (CD) and conventional and immunogold labelling Transmission Electron Microscopy (TEM). In buffered water solution, salmon calcitonin showed a two-stage conformational variation related to fibril formation and phase-separation of larger aggregates. A first stage, characterised by small conformational changes but a decrease in dichroic band intensity, was followed by a second stage, 6 days after, leading to higher conformational variations and aggregations. Salmon calcitonin showed a distinct modification in the secondary structure and aggregate morphology in the presence of hydrogen peroxide with respect to natural ageing, indicating that the two aggregation processes (natural and chemical-induced) followed a distinct mechanism. The oxidised forms of the peptide were separated by liquid chromatography. The same study was performed in the presence of DPPC liposomes. The results obtained by conventional and immunogold labelling TEM evidenced that salmon calcitonin in buffered water solution essentially does not enter the liposomes but forms around them a fibril network characterised by the same conformational changes after 6 days. The oxidised sample in the presence of liposomes showed a "fibrils hank", separated from liposomes. The presence of liposomes did not affect either the aggregation or the conformational modifications yet observed by TEM and CD in water solution.

  10. Nitric oxide synthase, calcitonin gene-related peptide and NK-1 receptor mechanisms are involved in GTN-induced neuronal activation

    DEFF Research Database (Denmark)

    Ramachandran, Roshni; Bhatt, Deepak Kumar; Ploug, Kenneth Beri;

    2014-01-01

    Infusion of glyceryltrinitrate (GTN), a nitric oxide (NO) donor, in awake, freely moving rats closely mimics a universally accepted human model of migraine and responds to sumatriptan treatment. Here we analyse the effect of nitric oxide synthase (NOS) and calcitonin gene-related peptide (CGRP...

  11. Contribution of kv7.4/kv7.5 heteromers to intrinsic and calcitonin gene-related Peptide-induced cerebral reactivity

    DEFF Research Database (Denmark)

    Chadha, Preet S; Jepps, Thomas A; Carr, Georgina;

    2014-01-01

    Middle cerebral artery (MCA) diameter is regulated by inherent myogenic activity and the effect of potent vasodilators such as calcitonin gene-related peptide (CGRP). Previous studies showed that MCAs express KCNQ1, 4, and 5 potassium channel genes, and the expression products (Kv7 channels) part...

  12. An Ongoing Role of α-Calcitonin Gene–Related Peptide as Part of a Protective Network Against Hypertension, Vascular Hypertrophy, and Oxidative Stress

    DEFF Research Database (Denmark)

    Smillie, Sarah-Jane; King, Ross; Kodji, Xenia;

    2014-01-01

    α-Calcitonin gene-related peptide (αCGRP) is a vasodilator, but there is limited knowledge of its long-term cardiovascular protective influence. We hypothesized that αCGRP protects against the onset and development of angiotensin II-induced hypertension and have identified protective mechanisms...

  13. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...

  14. De novo sequencing of two novel peptides homologous to calcitonin-like peptides, from skin secretion of the Chinese Frog, Odorrana schmackeri

    Directory of Open Access Journals (Sweden)

    Geisa P.C. Evaristo

    2015-09-01

    Full Text Available An MS/MS based analytical strategy was followed to solve the complete sequence of two new peptides from frog (Odorrana schmackeri skin secretion. This involved reduction and alkylation with two different alkylating agents followed by high resolution tandem mass spectrometry. De novo sequencing was achieved by complementary CID and ETD fragmentations of full-length peptides and of selected tryptic fragments. Heavy and light isotope dimethyl labeling assisted with annotation of sequence ion series. The identified primary structures are GCD[I/L]STCATHN[I/L]VNE[I/L]NKFDKSKPSSGGVGPESP-NH2 and SCNLSTCATHNLVNELNKFDKSKPSSGGVGPESF-NH2, i.e. two carboxyamidated 34 residue peptides with an aminoterminal intramolecular ring structure formed by a disulfide bridge between Cys2 and Cys7. Edman degradation analysis of the second peptide positively confirmed the exact sequence, resolving I/L discriminations. Both peptide sequences are novel and share homology with calcitonin, calcitonin gene related peptide (CGRP and adrenomedullin from other vertebrates. Detailed sequence analysis as well as the 34 residue length of both O. schmackeri peptides, suggest they do not fully qualify as either calcitonins (32 residues or CGRPs (37 amino acids and may justify their classification in a novel peptide family within the calcitonin gene related peptide superfamily. Smooth muscle contractility assays with synthetic replicas of the S–S linked peptides on rat tail artery, uterus, bladder and ileum did not reveal myotropic activity.

  15. Exercise alleviates hypoalgesia and increases the level of calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats

    Directory of Open Access Journals (Sweden)

    Patrícia Severo do Nascimento

    2012-09-01

    Full Text Available OBJECTIVE: The aim of this study was to evaluate the effects of treadmill training on nociceptive sensitivity and immunoreactivity to calcitonin gene-related peptide in the dorsal horn of the spinal cord of diabetic rats. METHODS: Male Wistar rats were divided into three groups: control, diabetic and trained diabetic. Treadmill training was performed for 8 weeks. The blood glucose concentrations and body weight were evaluated 48 h after diabetes induction and every 30 days thereafter. The nociceptive sensitivity was evaluated using the tail-flick apparatus. The animals were then transcardially perfused, and the spinal cords were post-fixed, cryoprotected and sectioned in a cryostat. Immunohistochemistry for calcitonin gene-related peptide analysis was performed on the dorsal horn of the spinal cord. RESULTS: The nociceptive sensitivity analysis revealed that, compared with the control and trained diabetic animals, the latency to tail deflection on the apparatus was longer for the diabetic animals. Optical densitometry demonstrated decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord in diabetic animals, which was reversed by treadmill training. CONCLUSION: We concluded that treadmill training can alleviate nociceptive hypoalgesia and reverse decreased calcitonin gene-related peptide immunoreactivity in the dorsal horn of the spinal cord of diabetic animals without pharmacological treatment.

  16. Comparison of reversible and nonreversible aqueous-soluble lipidized conjugates of salmon calcitonin.

    Science.gov (United States)

    Cheng, Weiqiang; Lim, Lee-Yong

    2008-01-01

    Reversible aqueous lipidization (REAL) at the interdisulfide bond has been shown to improve the deliverability of some peptide drugs. Recently, we developed a nonreversible aqueous lipidization method targeted at the interdisulfide bond of salmon calcitonin (sCT). The resultant derivative had comparable hypocalcemic activity to sCT after subcutaneous injection in rats, despite possessing significantly different biophysical properties. The purpose of this study was to conduct a comparative evaluation of the biophysical properties of the reversible aqueous-soluble lipidized sCT (REAL-sCT) and its corresponding nonreversible aqueous-soluble compound (Mal-sCT) with a view to correlate these properties to the bioactivities of the peptides. REAL-sCT and Mal-sCT were successfully synthesized, purified and identified. Both conjugates showed comparable retention times in a C-18 HPLC column, as well as robust helical structures and aggregation behavior in water, although REAL-sCT was shown by dynamic light scattering experiments to form larger aggregates than Mal-sCT in water. The larger particle size of REAL-sCT correlated with its stronger resistance to degradation by intestinal enzymes. Unlike Mal-sCT, REAL-sCT was rapidly converted to sCT in liver juice; however, the regenerated sCT appeared to degrade at a slower rate than unmodified sCT in the liver juice. Compared with sCT, REAL-sCT after subcutaneous injection as an aqueous solution at a dose of 0.15 mg/kg produced a prolonged hypocalcemic activity that lasted at least 24 h in the rat. Using a novel LC-MS/MS method that was developed for this study, we were able to show concomitant increases in REAL-sCT and sCT plasma concentrations with time, the latter prevailing at 10% the molar concentration of the former. In contrast, sCT was not present in the plasma following the subcutaneous injection of Mal-sCT, although a comparable hypocalcemic activity with shorter duration was observed. Oral administration of REAL

  17. Acylation of salmon calcitonin modulates in vitro intestinal peptide flux through membrane permeability enhancement.

    Science.gov (United States)

    Trier, Sofie; Linderoth, Lars; Bjerregaard, Simon; Strauss, Holger M; Rahbek, Ulrik L; Andresen, Thomas L

    2015-10-01

    Acylation of peptide drugs with fatty acid chains has proven beneficial for prolonging systemic circulation, as well as increasing enzymatic stability and interactions with lipid cell membranes. Thus, acylation offers several potential benefits for oral delivery of therapeutic peptides, and we hypothesize that tailoring the acylation may be used to optimize intestinal translocation. This work aims to characterize acylated analogues of the therapeutic peptide salmon calcitonin (sCT), which lowers blood calcium, by systematically increasing acyl chain length at two positions, in order to elucidate its influence on intestinal cell translocation and membrane interaction. We find that acylation drastically increases in vitro intestinal peptide flux and confers a transient permeability enhancing effect on the cell layer. The analogues permeabilize model lipid membranes, indicating that the effect is due to a solubilization of the cell membrane, similar to transcellular oral permeation enhancers. The effect is dependent on pH, with larger effect at lower pH, and is impacted by acylation chain length and position. Compared to the unacylated peptide backbone, N-terminal acylation with a short chain provides 6- or 9-fold increase in peptide translocation at pH 7.4 and 5.5, respectively. Prolonging the chain length appears to hamper translocation, possibly due to self-association or aggregation, although the long chain acylated analogues remain superior to the unacylated peptide. For K(18)-acylation a short chain provides a moderate improvement, whereas medium and long chain analogues are highly efficient, with a 12-fold increase in permeability compared to the unacylated peptide backbone, on par with currently employed oral permeation enhancers. For K(18)-acylation the medium chain acylation appears to be optimal, as elongating the chain causes greater binding to the cell membrane but similar permeability, and we speculate that increasing the chain length further may

  18. Calcitonin gene-related peptide (CGRP) regulates excitability and refractory period of the guinea pig ureter.

    Science.gov (United States)

    Maggi, C A; Giuliani, S

    1994-08-01

    Previous studies have indicated that calcitonin gene-related peptide (CGRP), released from the peripheral endings of capsaicin-sensitive primary afferent neurons, may play a role as an inhibitory transmitter in the guinea pig ureter. The aim of this study was to compare the effect of capsaicin desensitization and administration of a CGRP receptor antagonist on the excitability and refractory period of the guinea pig ureter to electrical field stimulation. Electrical field stimulation using a long (5 msec.) pulse width produced phasic contractions of the ureter which were unaffected by tetrodotoxin, that is, were produced through direct excitation of ureteral smooth muscle. Human alpha CGRP (1 to 10 nM.) produced a concentration-dependent transient suppression of the evoked contractions, and its effect was prevented by the CGRP receptor antagonist human alpha CGRP(8-37) (1 microM.). In vitro capsaicin pretreatment (10 microM. for 15 minutes) to block neuropeptide release from peripheral endings of sensory nerves or administration of the CGRP receptor antagonist enhanced the responsiveness of the guinea pig ureter to electrical stimulation. In control ureters, the application of two trains of electrical stimuli failed to produce a second contraction at intertrain intervals greater than 20 seconds. The intertrain interval required to obtain a second contraction averaging 50% of the amplitude of the first response (ITI50) of control ureters was about 50 seconds. In vitro capsaicin pretreatment or administration of the CGRP receptor antagonist reduced the refractory period of the ureter to electrical field stimulation: ITI50 averaged 8.8 and 9.1 seconds after capsaicin or CGRP antagonist pretreatment, respectively. These findings demonstrate that capsaicin pretreatment or blockade of CGRP receptors produced qualitatively and quantitatively similar excitatory effects on ureteral excitability and refractory period and are in general agreement with the idea that CGRP is a

  19. Serum calciotropic hormone levels,and dental fluorlsis in Children exposed to different concentrations of fluoride and iodine in drinking water

    Institute of Scientific and Technical Information of China (English)

    BA Yue; ZHANG Ya-wei; ZHU Jiang-yuan; YANG Yue-jin; YU Bo; HUANG Hui; WANG Gang; REN Li-jun; CHENG Xue-min; CUI Liu-xin

    2010-01-01

    Background High fluoride exposure can result in dental fluorosis.Fluoride and iodine are coexistent in the drinking water of areas in China and may affect the prevalence of dental fluorosis and osteogenesis.The aim of this study was to investigate the relationship between serum calciotropic hormone level.and dentaI fluorisis in children exposed to different concentrations of fluoride and iodine in drinking water.Methods A pilot study was conducted in three villages located in the Kaifeng and Tongxu counties of Henan Province,China in 2006.Children aged 8 to 12 years.born and raised in the three villages were recruited.The fluoride levels in the samples of urine from these children were detected by fluoride ion selective electrode.Calcitonin and osteocalcin levels in the serum,and serum calcium were measured by radioimmunassay and flame atomic absorption spectrometry, respectively.Results Fluoride levels in urine were significantly lower in children from control area(CA)as compared with those from the high fluoride & iodine areas(HFIA)and the high fluoride area(HFA)(P<0.05 respectively),and no statistically significant difference was found between the children from HFIA and HFA.Additionally,calcitonin levels in the serum were significantly lower in children from CA and HFA as compared with that from HFIA(P<0.05 respectively),and osteocalcin levels in the serum was lower in children from CA than those from HFIA (P<0.05).No statistically significant difference in serum osteocalcin concentrations was found between children from HFA and HFIA.Conclusion This study provides an evidence that iodine exposure may modify the serum calciotropic hormone levels related to fluorine exposure.

  20. Abnormal Basal Ganglia Functional Connectivity in Idiopathic Generalized Epilepsy

    Institute of Scientific and Technical Information of China (English)

    Cheng Luo; Yang Xia; Zhi-Wei Guo; Dong Zhou

    2011-01-01

    The basal ganglia have been implicated in a modulation role in idiopathic generalized epilepsy (IGE) by an invasive electrophysioigic means.This paper investigates the basal ganglia functional connectivity by using the region-wise functional connection analysis in resting-state functional magnetic resonance imaging (fMRi) in IGE.The increased functional connectivity within basal ganglia,and between the basal ganglia and the thalamus,and decreased functional connectivity between basal ganglia and motor cortex are found in IGE compared with the controls. These findings not only implicate dysfunctional integration in the motor loop in IGE and the enhanced interaction in the modulated loop,but also suggest that the basal ganglia modulate the generalized epileptic discharges with the influence over thalamus in the corticothalamus network.

  1. 鲑鱼降钙素治疗老年糖尿病并发骨质疏松的效果分析%Efficacy analysis of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis

    Institute of Scientific and Technical Information of China (English)

    李洪昌; 廖浩峰; 邓颖玉

    2015-01-01

    Objective To investigate the efficacy of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis. Methods 70 patients with senile diabetes complicated with osteoporosis were selected as research objects and randomly divided into control group and observation group.Calcium carbonate D3 tablet was used in control group,calcium carbonate D3 tablet combined with salmon calcitonin were applied in observation group.The pain degree, effect and the level of serum BMD,BGP,AKP and PTH in two groups were compared.The adverse reaction in two groups were recorded. Results After treatment,the pain degree of observation group was significantly improved,and significantly better than that of control group (P<0.05).After treatment,the level of BMD,BGP in observation group was significantly higher than that in control group and before treatment respectively(P<0.05).After treatment,the level of AKP,PTH in ob-servation group was significantly lower than in control group and before treatment respectively (P<0.05).Total effective rate of observation group was 94.3%,significantly higher than that of control group(77.1%)(P<0.05).The incidence rate of adverse reaction in observation group was significantly lower than that in control group(P<0.05). Conclusion The clini-cal efficacy of salmon calcitonin in the treatment of senile diabetes complicated with osteoporosis is significant.%目的:探讨鲑鱼降钙素治疗老年糖尿病并发骨质疏松的效果。方法选取70例老年糖尿病并发骨质疏松患者为研究对象,随机分为对照组和观察组,对照组给予碳酸钙D3片治疗,观察组采用碳酸钙D3片联合鲑鱼降钙素治疗,比较两组的疼痛程度、治疗效果及血清BMD、BGP、AKP及PTH含量,记录两组不良反应发生情况。结果观察组治疗后的疼痛程度明显改善,且明显好于对照组(P<0.05);观察组治疗后的BMD、BGP水平高于对照组及治疗前(P<0.05);观察组治

  2. Protein electrophoresis - serum

    Science.gov (United States)

    ... this page: //medlineplus.gov/ency/article/003540.htm Protein electrophoresis - serum To use the sharing features on ... JavaScript. This lab test measures the types of protein in the fluid (serum) part of a blood ...

  3. Negative pressure for diabetic foot:Evaluation based on calcitonin gene-related peptide in the limb skin of dogs

    Institute of Scientific and Technical Information of China (English)

    Rui Ling; Jun Yi; Ling Wang; Mofan Ning

    2006-01-01

    BACKGROUND: Very good therapeutic effect has been obtained for limb negative pressure in treating limb ischemic diseases.But its mechanism in treating diabetic foot needs further investigation.OBJECTIVE:To observe the changes of calcitonin gene related peptide(CGRP)in sensory nerve fiber of skin of dogs with diabetic foot before and after limb negative pressure treatment,and make a comparison with normal dogs,then analyze the mechanism of limb negative pressure in treating diabetic foot.DESIGN:A randomized controlled animal experiment.SETTING:Third Department of General Surgery,Xijing Hospital,Fourth Military Medical University of Chinese PLA.MATERIALS:Fifteen healthy hybrid dogs,of either gender,weighing 12-18 kg,were provided by Animal Room,Xijing Hospital of the Fourth Military Medical University of Chinese PLA.After being numbered,the involved dogs were randomly assigned into 3 groups:treatment group,model group and normal control group,5 dogs each.Limb negative pressure therapeutic machine(self-made);Anti-CGRP serum (primary antibody,Watpa Company,England);rabbit anti-BigG(second antibody),ABC compound solution,DAB reagent,glucose oxidase reagent,Tdxon-X100 solution(Sigma company,USA),ammonium nickelous sulfate reagent(Xi'an Chemical Reagent Factory),neutral gum-solution(import,Shanghai Reagent Co.,Ltd.);Leitz1400 sliding freezing microtome(Leitz Company,Germany);Leica 1800 cryostat microtome(Leica Company,Germany);Quantimet570 image analyzer(Leica Company,Germany).METHODS:This experiment was carried out in the Animal Room,Xijing Hospital,Fourth Military Medical University of Chinese PLA from October 2005 to June 2006.①After the dogs in the treatment and model groups were anesthetized,their pancreatic tissues were removed completely and animal models of type I diabetes mellitus were developed.All the femoral artery branches including deep femoral artery were ligated and cut off.A helical wire was inserted into the distal femoral artery cavity for narrowing

  4. Basal cell carcinoma in oculo-cutaneous albinism

    Directory of Open Access Journals (Sweden)

    Ajay Kumar

    2016-06-01

    Full Text Available The basal cell carcinoma is the most common skin tumour especially affecting the white individuals worldwide. The exact incidence of basal cell carcinoma is not known from India but non melanoma skin cancers comprises about 1-2% of cutaneous tumour in India. The most common skin tumour is squamous cell carcinoma in albinism and the incidence of basal cell carcinoma is less. Hereby, we report a peculiar case of basal cell carcinoma in albinism to highlights the importance of early recognition and diagnosis of suspected lesions by performing histopathological examination in unusual circumstances. [Int J Res Med Sci 2016; 4(6.000: 2452-2454

  5. Serum iron test

    Science.gov (United States)

    Fe+2; Ferric ion; Fe++; Ferrous ion; Iron - serum; Anemia - serum iron; Hemochromatosis - serum iron ... A blood sample is needed. Iron levels are highest in the morning. Your health care provider will likely have you do this test in the morning.

  6. Nevoid basal cell carcinoma syndrome (Gorlin syndrome

    Directory of Open Access Journals (Sweden)

    Lo Muzio Lorenzo

    2008-11-01

    Full Text Available Abstract Nevoid basal cell carcinoma syndrome (NBCCS, also known as Gorlin syndrome, is a hereditary condition characterized by a wide range of developmental abnormalities and a predisposition to neoplasms. The estimated prevalence varies from 1/57,000 to 1/256,000, with a male-to-female ratio of 1:1. Main clinical manifestations include multiple basal cell carcinomas (BCCs, odontogenic keratocysts of the jaws, hyperkeratosis of palms and soles, skeletal abnormalities, intracranial ectopic calcifications, and facial dysmorphism (macrocephaly, cleft lip/palate and severe eye anomalies. Intellectual deficit is present in up to 5% of cases. BCCs (varying clinically from flesh-colored papules to ulcerating plaques and in diameter from 1 to 10 mm are most commonly located on the face, back and chest. The number of BBCs varies from a few to several thousand. Recurrent jaw cysts occur in 90% of patients. Skeletal abnormalities (affecting the shape of the ribs, vertebral column bones, and the skull are frequent. Ocular, genitourinary and cardiovascular disorders may occur. About 5–10% of NBCCS patients develop the brain malignancy medulloblastoma, which may be a potential cause of early death. NBCCS is caused by mutations in the PTCH1 gene and is transmitted as an autosomal dominant trait with complete penetrance and variable expressivity. Clinical diagnosis relies on specific criteria. Gene mutation analysis confirms the diagnosis. Genetic counseling is mandatory. Antenatal diagnosis is feasible by means of ultrasound scans and analysis of DNA extracted from fetal cells (obtained by amniocentesis or chorionic villus sampling. Main differential diagnoses include Bazex syndrome, trichoepithelioma papulosum multiplex and Torre's syndrome (Muir-Torre's syndrome. Management requires a multidisciplinary approach. Keratocysts are treated by surgical removal. Surgery for BBCs is indicated when the number of lesions is limited; other treatments include laser

  7. [Vismodegib Therapy for Periocular Basal Cell Carcinoma].

    Science.gov (United States)

    Keserü, M; Green, S; Dulz, S

    2017-01-01

    Background Basal cell carcinoma (BCC) is the commonest periorbital tumour. Mohs' micrographic surgery and secondary reconstruction is the therapeutic gold standard for periorbital BCC. In cases of inoperability for any reason, therapeutic alternatives are needed. Since the approval of vismodegib, an orally administered, targeted BCC therapy is available. Nevertheless there is little information on the use of vismodegib for periorbital BCC. Patients and Methods In a retrospective study, we analysed the data of 4 patients treated with vismodegib since 2014. The patients' mean age before starting therapy was 87 years. The mean maximum tumour diameter was 22.0 mm. Results The median follow-up was 17 months. The median treatment duration was 7.5 months. In 75 % of patients, complete clinical remission of BCC was achieved. In 25 % of patients, interim stabilisation of tumour growth was possible. The most common side effect of therapy was muscle spasm. Conclusion Vismodegib is an effective treatment option for patients with periorbital BCC, in whom surgical treatment is not possible for any reason.

  8. How Basal Ganglia Outputs Generate Behavior

    Directory of Open Access Journals (Sweden)

    Henry H. Yin

    2014-01-01

    Full Text Available The basal ganglia (BG are a collection of subcortical nuclei critical for voluntary behavior. According to the standard model, the output projections from the BG tonically inhibit downstream motor centers and prevent behavior. A pause in the BG output opens the gate for behavior, allowing the initiation of actions. Hypokinetic neurological symptoms, such as inability to initiate actions in Parkinson’s disease, are explained by excessively high firing rates of the BG output neurons. This model, widely taught in textbooks, is contradicted by recent electrophysiological results, which are reviewed here. In addition, I also introduce a new model, based on the insight that behavior is a product of closed loop negative feedback control using internal reference signals rather than sensorimotor transformations. The nervous system is shown to be a functional hierarchy comprising independent controllers occupying different levels, each level controlling specific variables derived from its perceptual inputs. The BG represent the level of transition control in this hierarchy, sending reference signals specifying the succession of body orientations and configurations. This new model not only explains the major symptoms in movement disorders but also generates a number of testable predictions.

  9. Involvement of calcitonin gene-related peptide in migraine: regional cerebral blood flow and blood flow velocity in migraine patients

    DEFF Research Database (Denmark)

    Lassen, L.H.; Jacobsen, V.B.; Haderslev, P.A.

    2008-01-01

    g/min) or placebo for 20 min was studied in 12 patients with migraine without aura outside attacks. Xenon-133 inhalation SPECT-determined regional cerebral blood flow (rCBF) and transcranial Doppler (TCD)-determined blood velocity (V-mean) in the middle cerebral artery (MCA), as well as the heart......Calcitonin gene-related peptide (CGRP)-containing nerves are closely associated with cranial blood vessels. CGRP is the most potent vasodilator known in isolated cerebral blood vessels. CGRP can induce migraine attacks, and two selective CGRP receptor antagonists are effective in the treatment...... of migraine attacks. It is therefore important to investigate its mechanism of action in patients with migraine. We here investigate the effects of intravenous human alpha-CGRP (h alpha CGRP) on intracranial hemodynamics. In a double-blind, cross-over study, the effect of intravenous infusion of haCGRP (2 mu...

  10. Application of shock waves to rat skin decreases calcitonin gene-related peptide immunoreactivity in dorsal root ganglion neurons.

    Science.gov (United States)

    Takahashi, Norimasa; Wada, Yuichi; Ohtori, Seiji; Saisu, Takashi; Moriya, Hideshige

    2003-09-30

    There have been several reports on the use of extracorporeal shock waves in the treatment of pseudarthrosis, calcifying tendinitis, and tendinopathies of the elbow. However, the pathomechanism of pain relief has not been clarified. To investigate the analgesic properties of shock wave application, we analyzed changes in calcitonin gene-related peptide (CGRP)-immunoreactive (ir) dorsal root ganglion (DRG) neurons. In the nontreated group, fluorogold-labeled dorsal root ganglion neurons innervating the most middle foot pad of hind paw were distributed in the L4 and L5 dorsal root ganglia. Of these neurons, 61% were CGRP-ir. However, in the shock wave-treated group, the percentage of FG-labeled CGRP-ir DRG neurons decreased to 18%. These data show that relief of clinical pain after shock wave application may result from reduced CGRP expression in DRG neurons.

  11. Occurrence of substance P, vasoactive intestinal peptide, and calcitonin gene-related peptide in dermographism and cold urticaria.

    Science.gov (United States)

    Wallengren, J; Möller, H; Ekman, R

    1987-01-01

    Substance P (SP), calcitonin gene-related peptide (CGRP), and vasoactive intestinal peptide (VIP) were assayed in lesions and normal skin of patients with dermographism and cold urticaria utilizing suction-induced blisters. There was no difference in SP and VIP concentrations between challenged and control skin of urticaria patients. On the whole, however, the concentration of both neuropeptides, and VIP in particular, was higher in the urticaria patients than in control subjects. CGRP levels were not increased. SP and VIP in blood samples from veins draining challenged skin areas were below the detection limit. It is concluded that SP and VIP may potentiate histamine in wheal formation and thus contribute to the increased reactivity of the skin to trauma and temperature changes in patients with physical urticaria.

  12. A Prognostic Dilemma of Basal Cell Carcinoma with Intravascular Invasion

    Science.gov (United States)

    Niumsawatt, Vachara; Castley, Andrew

    2016-01-01

    Summary: Basal cell carcinoma is the most common malignancy; however, it very rarely metastasizes. Despite the low mortality caused by this cancer, once it spreads, it has dim prognosis. We report a case of basal cell carcinoma with rare intravascular invasion and review the literature for risk factors and management of metastasis.

  13. Mineralizing angiopathy with basal ganglia stroke in an infant

    Directory of Open Access Journals (Sweden)

    Puneet Jain

    2015-01-01

    Full Text Available Basal ganglia stroke is known following trivial head trauma. Recently a distinct clinic-radiological entity termed ′mineralizing angiopathy′ was described. We report an infant who developed basal ganglia stroke following trivial fall. His clinic-radiological features are described.

  14. Vismodegib resistance in basal cell carcinoma: not a smooth fit.

    Science.gov (United States)

    Ridky, Todd W; Cotsarelis, George

    2015-03-09

    In this issue of Cancer Cell, two complementary papers by Atwood and colleagues and Sharpe and colleagues show that basal cell carcinomas resistant to the Smoothened (SMO) inhibitor vismodegib frequently harbor SMO mutations that limit drug binding, with mutations at some sites also increasing basal SMO activity.

  15. Evolution and diversification of the basal transcription machinery.

    Science.gov (United States)

    Duttke, Sascha H C

    2015-03-01

    Transcription initiation was once thought to be regulated primarily by sequence-specific transcription factors with the basal transcription machinery being largely invariant. Gradually it became apparent that the basal transcription machinery greatly diversified during evolution and new studies now demonstrate that diversification of the TATA-binding protein (TBP) family yielded specialized and largely independent transcription systems.

  16. Formulation, stability and pharmacokinetics of sugar-based salmon calcitonin-loaded nanoporous/nanoparticulate microparticles (NPMPs) for inhalation.

    Science.gov (United States)

    Amaro, Maria Inês; Tewes, Frederic; Gobbo, Oliviero; Tajber, Lidia; Corrigan, Owen I; Ehrhardt, Carsten; Healy, Anne Marie

    2015-04-10

    A challenge exists to produce dry powder inhaler (DPI) formulations with appropriate formulation stability, biological activity and suitable physicochemical and aerosolisation characteristics that provide a viable alternative to parenteral formulations. The present study aimed to produce sugar-based nanoporous/nanoparticulate microparticles (NPMPs) loaded with a therapeutic peptide - salmon calcitonin (sCT). The physicochemical properties of the powders and their suitability for pulmonary delivery of sCT were determined. Production of powders composed of sCT loaded into raffinose or trehalose with or without hydroxypropyl-β-cyclodextrin was carried out using a laboratory scale spray dryer. Spray dried microparticles were spherical, porous and of small geometric size (≤2 μm). Aerodynamic assessment showed that the fine particle fraction (FPF) less than 5 μm ranged from 45 to 86%, depending on the formulation. The mass median aerodynamic diameter (MMAD) varied between 1.9 and 4.7 μm. Compared to unprocessed sCT, sCT:raffinose composite systems presented a bioactivity of approximately 100% and sCT:trehalose composite systems between 70-90% after spray drying. Storage stability studies demonstrated composite systems with raffinose to be more stable than those containing trehalose. These sugar-based salmon calcitonin-loaded NPMPs retain reasonable sCT bioactivity and have micromeritic and physicochemical properties which indicate their suitability for pulmonary delivery. Formulations presented a similar pharmacokinetic profile to sCT solution. Hence the advantage of a dry powder formulation is its non-invasive delivery route and ease of administration of the sCT.

  17. CGRP-RCP, a novel protein required for signal transduction at calcitonin gene-related peptide and adrenomedullin receptors.

    Science.gov (United States)

    Evans, B N; Rosenblatt, M I; Mnayer, L O; Oliver, K R; Dickerson, I M

    2000-10-06

    It is becoming clear that receptors that initiate signal transduction by interacting with G-proteins do not function as monomers, but often require accessory proteins for function. Some of these accessory proteins are chaperones, required for correct transport of the receptor to the cell surface, but the function of many accessory proteins remains unknown. We determined the role of an accessory protein for the receptor for calcitonin gene-related peptide (CGRP), a potent vasodilator neuropeptide. We have previously shown that this accessory protein, the CGRP-receptor component protein (RCP), is expressed in CGRP responsive tissues and that RCP protein expression correlates with the biological efficacy of CGRP in vivo. However, the function of RCP has remained elusive. In this study stable cell lines were made that express antisense RCP RNA, and CGRP- and adrenomedullin-mediated signal transduction were greatly reduced. However, the loss of RCP did not effect CGRP binding or receptor density, indicating that RCP did not behave as a chaperone but was instead coupling the CGRP receptor to downstream effectors. A candidate CGRP receptor named calcitonin receptor-like receptor (CRLR) has been identified, and in this study RCP co-immunoprecipitated with CRLR indicating that these two proteins interact directly. Since CGRP and adrenomedullin can both signal through CRLR, which has been previously shown to require a chaperone protein for function, we now propose that a functional CGRP or adrenomedullin receptor consists of at least three proteins: the receptor (CRLR), the chaperone protein (RAMP), and RCP that couples the receptor to the cellular signal transduction pathway.

  18. Direct interactions between calcitonin-like receptor (CLR) and CGRP-receptor component protein (RCP) regulate CGRP receptor signaling.

    Science.gov (United States)

    Egea, Sophie C; Dickerson, Ian M

    2012-04-01

    Calcitonin gene-related peptide (CGRP) is a neuropeptide with multiple neuroendocrine roles, including vasodilation, migraine, and pain. The receptor for CGRP is a G protein-coupled receptor (GPCR) that requires three proteins for function. CGRP binds to a heterodimer composed of the GPCR calcitonin-like receptor (CLR) and receptor activity-modifying protein (RAMP1), a single transmembrane protein required for pharmacological specificity and trafficking of the CLR/RAMP1 complex to the cell surface. In addition, the CLR/RAMP1 complex requires a third protein named CGRP-receptor component protein (RCP) for signaling. Previous studies have demonstrated that depletion of RCP from cells inhibits CLR signaling, and in vivo studies have demonstrated that expression of RCP correlates with CLR signaling and CGRP efficacy. It is not known whether RCP interacts directly with CLR to exert its effect. The current studies identified a direct interaction between RCP and an intracellular domain of CLR using yeast two-hybrid analysis and coimmunoprecipitation. When this interacting domain of CLR was expressed as a soluble fusion protein, it coimmunoprecipitated with RCP and inhibited signaling from endogenous CLR. Expression of this dominant-negative domain of CLR did not significantly inhibit trafficking of CLR to the cell surface, and thus RCP may not have a chaperone function for CLR. Instead, RCP may regulate CLR signaling in the cell membrane, and direct interaction between RCP and CLR is required for CLR activation. To date, RCP has been found to interact only with CLR and represents a novel neuroendocrine regulatory step in GPCR signaling.

  19. Low Serum 25-Hydroxyvitamin D Concentrations Are Associated with Increased Risk for Melanoma and Unfavourable Prognosis

    OpenAIRE

    Benjamin Bade; Alexander Zdebik; Stefan Wagenpfeil; Stefan Gräber; Jürgen Geisel; Thomas Vogt; Jörg Reichrath

    2014-01-01

    Background Low vitamin D status (serum 25(OH)D concentration) is associated with increased incidence and unfavourable outcome of various types of cancer. However, there are limited data on influence of serum 25(OH)D on risk and prognosis of malignant melanoma. Methods Basal serum 25(OH)D concentrations were retrospectively analyzed in a cohort of melanoma patients (n = 324) and healthy controls (n = 141). We tested the hypothesis that serum 25(OH)D concentrations are predictive of melanoma ri...

  20. Basal ganglia - thalamus and the crowning enigma

    Directory of Open Access Journals (Sweden)

    Marianela eGarcia-Munoz

    2015-11-01

    Full Text Available When Hubel (1982 referred to layer 1 of primary visual cortex as …a ‘crowning mystery’ to keep area-17 physiologists busy for years to come... he could have been talking about any cortical area. In the 80’s and 90’s there were no methods to examine this neuropile on the surface of the cortex: a tangled web of axons and dendrites from a variety of different places with unknown specificities and doubtful connections to the cortical output neurons some hundreds of microns below. Recently, three changes have made the crowning enigma less of an impossible mission: the clear presence of neurons in layer 1 (L1, the active conduction of voltage along apical dendrites and optogenetic methods that might allow us to look at one source of input at a time. For all of those reasons alone, it seems it is time to take seriously the function of L1. The functional properties of this layer will need to wait for more experiments but already L1 cells are GAD67 positive, i.e., inhibitory! They could reverse the sign of the thalamic glutamate (GLU input for the entire cortex. It is at least possible that in the near future normal activity of individual sources of L1 could be detected using genetic tools. We are at the outset of important times in the exploration of thalamic functions and perhaps the solution to the crowning enigma is within sight. Our review looks forward to that solution from the solid basis of the anatomy of the basal ganglia output to motor thalamus. We will focus on L1, its afferents, intrinsic neurons and its influence on responses of pyramidal neurons in layers 2/3 and 5. Since L1 is present in the whole cortex we will provide a general overview considering evidence mainly from the somatosensory cortex before focusing on motor cortex.

  1. 鲑鱼降钙素新型注射用温度敏感原位凝胶系统的构建及评价%Preparation and characterization of a novel injectable thermosensitive in situ gel containing salmon calcitonin

    Institute of Scientific and Technical Information of China (English)

    丁维明; 李艳芳; 李桂玲

    2014-01-01

    Objective To prepare the thermosensitive in situ gel of salmon calcitonin for injection and evaluate the characteristics and hypocalcemic effect. Methods Poloxamer F127 and poloxamer F68 were used to prepare the thermosensitive gel of samon calcitonin. The characteristics of the gel, such as gelation temperature, gelation time, rheological behavior and texture characteristics, were evaluated. Blood samples were drawn from orbit in rats, and coloration methods were used to monitor serum calcium ion concentration in order to study in vivo drug release and the hypocalcemic effect. Results The gelation temperature of the salmon calcitonin-loaded in situ gel was (35.3 ± 1.3)℃, and the gelation time was (108.3 ± 5.5) s. The in situ gel, a fluid solution at 25 ℃, became semisolid quickly at 37 ℃ due to the fact the viscosity and mechanical parameters such as gel strength for gel was enhanced at 37℃. The in situ gel loading sCT clearly decreased serum calcium level in rats over a longer period of time as compared with the conventional injection indicating sustained characteristic in vivo, and produced 138.6%hypocalcemic efficacy relative to common injection. Conclusion The thermosensitive in situ gel delivery system may be a promising candidate for injectable sustained delivery of salmon calcitonin.%目的构建鲑鱼降钙素新型注射用温度敏感原位凝胶系统并对其胶凝特性和降血钙效应进行评价。  方法以泊洛沙姆 F127为主要基质材料,复合使用泊洛沙姆 F68,制备鲑鱼降钙素注射用温度敏感原位凝胶给药系统,以胶凝温度、胶凝时间、流变学、质构特性为考察指标,对该凝胶系统性质进行评价;采用大鼠眼眶取血,钙显色法监测体内血清钙离子浓度,对该凝胶系统降血钙效应进行研究。  结果所制备的鲑鱼降钙素注射用温度敏感原位凝胶的胶凝温度为(35.3±1.3)℃,胶凝时间为(108.3±5.5)s,在25℃

  2. Serum testosterone, DHEA-S and androstenedione levels in acne

    Directory of Open Access Journals (Sweden)

    Hatwal A

    1990-01-01

    Full Text Available Basal serum levels of total testosterone, dehydroepiandosterone sulfate (DHEA, - S and androstenedione (A4 were measured by radioimmunoassay in 100 patients of acne vulgaris, and in 100 age and sex matched acne free healthy subjects. In males with acne the mean serum testosterone levels were marginally and the DHEAS and A4A levels were significantly higher as compared to controls (p. Females with acne had significantly higher levels of testosterone (p< 0.001, DHEA-S (p< 0.001 and (p < 0.01 than controls. Our data suggest that increased adrenal androgen levels in plasma may be responsible for treatment resistant acne vulgarism

  3. Treatment on osteopenia of maintenance hemodialysis patients with salmon calcitonin%鲑鱼降钙素治疗维持性血液透析骨量减少的患者

    Institute of Scientific and Technical Information of China (English)

    张东亮; 尹道馨; 郭王; 林雅慧; 刘文虎

    2008-01-01

    Objective To study the effect of long-term salmon calcitonin on bone mineral density (BMD), bone metabolism biochemical indicators and subjective score of bone pain in maintenance hemedialysis (MHD) patients with osteopenia. Methods Thirty-four MHD patients diagnosed as osteopenia by dual-energy X-ray absorptiometry (DXEA) were enrolled in this study. All the patients were treated with hypodermic injection of salmon calcitonin (50 U, thrice a week) for 12 months. The detecting parameters were as follows: BMD with DEXA in lumbar spine (L1-L4), femoral neck, troch, inter, and Ward's triangle before and after the study;serum bone metabolism biochemical indicators before and 6 and 12 months after the study;subjective scores of bone pain before and 1, 6, and 12 months after the study. Results Thirty-two patients were followed-up successfully. As compared to BMD parameters before study, the total T-score (-1.98± 2.20 vs 1.26±1.88, P=0.009) and total Z-score (-0.90±2.15 vs 0.08±2.05, P=0.002) of lumbar spine, the total T-score (-1.72±1.53 vs 1.06±1.58, P=0.016) and totle Z-score (-0.66±0.80 vs 0.08±1.08, P=0.029) of hip, the T-score of L3 (-2.02±2.51 vs 1.24±2.02, P=0.033), the Z-score of L2 (-0.44±1.82 vs 0.06±1.63, P=0.016), the Z-score of femoral troch (-0.65±1.11 vs 0.48±1.12, P=0.034) and the Z-score of inter (-0.58±0.94 vs 0.02±1.12, P=0.006) were increased significantly after study. But there were no significant differences in other examined regions and serum biochemical parameters. The subjective scores of bone pain were decreased rapidly for 41.7% after 1 month (P<0.01) and 76.6% after 6 months (P<0.01). The subjective score of bone pain after 12 months was similar to 6 months. The side effects of salmon calcitonin included nausea and vomitting in 5 cases (14.71%, 5/34), dizziness, blushing and flustered in 1 case respectively (3.13%,1/32). Conclusions Long-term hypodermic injection of salmon calcitonin can improve BMD and bone pain for MHD

  4. Mouse Model for Spontaneous Basal-Like Breast Cancer%自发Basal-like乳腺癌小鼠模型研究

    Institute of Scientific and Technical Information of China (English)

    张丹芳; 孙保存; 赵秀兰; 崔艳芬; 徐少艳; 董学易; 车娜

    2011-01-01

    过程中起重要作用.%Objective: Basal-like breast cancer is very Invasive and highly metastatlc with poor prognosis. The molecular mechanisms underlying its tumorigenesis and tumor progression remain unclear, and ideal animal models are lacking. The present study aims to identify the features of spontaneous breast cancer in TA2 mice, to determine whether the mouse model is useful and relevant for human basal-like breast cancer, and to investigate the relationship among pregnancy, mouse mammary tumor virus ( MMTV), and TA2 breast cancer. Methods: Spontaneous breast cancers were collected from 84 female TA2 mice. The metastasis, morphology, and inimun-ophenotype of the TA2 mice bearing breast cancer tumors were determined using hematoxylin, eosin staining, and immunnohistocherms-try, respectively. The similarities between the basal-like breast cancers of the animals and that of the human patients were compared Electrochcmilumincsccnce immunoassay was used to detect the serum levels of estradiol ( E2 ) and progesterone in the TA2 mice (n = 10 ), the mice at dl 5 during the gestation period (n = 6 ), and the normal mice ( n = 6). The MMTV in the TA2 breast cancer cells were checked under electron microscopy ( EM ). The MMTV LTR expression in the mammary glands of the normal and the pregnant mice and the TA2 mice were determined using reverse transcriptase polymerase chain reaction. Results: The spontaneous breast cancer tissues in the TA2 mice were similar to human basal-like breast cancer in terms of biology, morphology, and phenotype. The mean age of the TA2 mice at tumorigenesis was ( 329.81 ± 95.32 ) d, and the mean frequency of delivery was (2.70 ± 1.8 ), with rapid tumor growth within the gestation period. Metastasis in the visceral organs frequently occurred in TA2 tumors. However, nodal metastasis was not found in the current research. Pulmonary metastasis was seen in 80% ( 64/80 ) of the tumors. The TA2 cancers were homologous in histomorphology. The cancer nest consisted of roundlel cells with

  5. Clinical research study of Familial Idiopathic Basal Ganglia Calcification from 8 family analysis%8个家族性特发性基底节钙化家系患者的临床研究

    Institute of Scientific and Technical Information of China (English)

    黄远桃; 张伟; 邹国英; 李萍; 周高雅; 杨敏慧; 向光红; 周宏灏

    2016-01-01

    目的:探讨8个家族性特发性基底节钙化(familial idiopathic basal ganglia calcification,FIBGC)家系患者的临床特点。方法收集8个FIBGC家系患者的临床资料,分析患者的临床检验结果、头颅CT及MRI改变、发病年龄、临床表现与患者基底节钙化体积(the volume of basal ganglia calcification,VBGC)的关系。结果家系患者和健康成员血清钙、铝、砷、钴、镁、磷、铁、甲状旁腺激素和降钙素的值比较均无显著性差异(P>0.05)。8个家系包括两个近亲结婚的家系均呈现常染色体显性遗传;运动受损患者的病情严重程度与基底节区钙化的病灶大小相关;精神症状的患者有无症状与VBGC的大小无关;运动受损与精神症状的患者间发表年龄(43.954±2.473 vs.31.319±10.156 y, t=4.438, P=0.001)和VBGC (1.748±0.622 vs.0.392±0.276 cm3, t=2.518, P=0.028)比较有统计学差异。结论8个FIBGC家系患者呈现常染色体显性遗传的特点,运动受损的患者基底节区钙化的病灶大,发病年龄较晚;精神症状的患者基底节区钙化的病灶小,发病年龄较早。%Objective To better understand the clinical characteristics of Familial Idiopathic Basal Ganglia Calcifi⁃cation (FIBGC), including at the perspective of hereditary pattern, clinical test results, onset age, clinical heterogeneity and the volume of basal ganglia calcification (VBGC). Method 8 Eight FIBGC families were collected and draw family pedigrees were draw. Analysis of was conducted on the patient's clinical test results, head CT and MRI changes, onset ag⁃es, relationship of clinical manifestations with VBGC. Results No significant difference was found in serum calcium, alu⁃minum, arsenic, cobalt, magnesium, phosphorus, iron, parathyroid hormone and calcitonin concentration between the fam⁃ily members of patients and healthy controls (P>0.05). Family members from 8 FIBGC families including the two with

  6. Evaluation of /sup 99m/Tc diphosphonate kinetics and bone scans in patients with Paget's disease before and after calcitonin treatment

    Energy Technology Data Exchange (ETDEWEB)

    Waxman, A.D.; Ducker, S.; McKee, D.; Siemsen, J.K.; Singer, F.R.

    1977-12-01

    Eleven patients with Paget's disease of bone underwent serial total body bone scans before and after therapy with calcitonin. All patients studied showed improvement clinically as well as biochemically. Scan improvement was noted in patients with mild disease. Patients with severe disease showed either no change or only slight improvement on the serial bone scans. The scan was of greatest value in determining the extent of disease, especially in 3 patients in whom biochemical values were normal. A single pulse injection of 50 M.R.C. units of salmon calcitonin produced a significant increase in the blood clearance of /sup 99m/Tc diphosphonate. The mechanism of this effect is not clear from this study.

  7. İdiopatik-post menopozal-senil osteoporozun ağrılı akut epizodlarının calcitonin ile tedavisi

    OpenAIRE

    Kokino, Siranus

    2004-01-01

    Bakırköy Fizik Tedavi ve Rehabilitasyon Merkezi'nde yapmış olduğumuz idiopatik veya sekonder osteoporozun ağrılı akut epizodlarının Salmon-Calcitonin tedavisi ile ilgili çalışmamız 31'i kadın 2'si erkek, 33 hasta üzerinde incelenmiştir. Deneklerimize çalışma süresi boyunca klinik tablonun şiddetine ve hastanın ilaca toleransına göre günlük 50100 UI Salmon Calcitonin tedavisi uygulanmıştır. İlacın çalışma süresince laboratuar parametrelerde anlamlı bir değişme saptanmamış, fonksiyonel yetm...

  8. Oral absorption enhancement of salmon calcitonin by using both N-trimethyl chitosan chloride and oligoarginines-modified liposomes as the carriers.

    Science.gov (United States)

    Huang, Aiwen; Su, Zhigui; Li, Sai; Sun, Minjie; Xiao, Yanyu; Ping, Qineng; Deng, Yanping

    2014-08-01

    In this study both N-trimethyl chitosan chloride (TMC) and oligoarginine (Arg8) were utilized to modify liposomes as the multifunctional carriers (TMC-Arg8-Lips) for enhancing the oral absorption of salmon calcitonin. Two permeation enhancers with positive charges were sequentially adsorbed on the liposomal surface with negative charges by electrostatic interaction. Instead of salmon calcitonin, fluorescein isothiocyanate dextran (FD4) was loaded in TMC-Arg8-Lips for Caco-2 cell permeation test in vitro and penetration examination in rat intestinal tract in vivo. The results showed that the apparent permeability coefficient (Papp) of TMC-Arg8-Lips containing FD4 were 7.0-, 4.4-, 1.8- and 1.4-folds higher than FD4 solution, FD4-TMC solution, non-modified liposomes (Non-Lips) and TMC modified liposomes (TMC-Lips), respectively. A strong fluorescence was observed by confocal laser scanning microscope (CLSM) at rat intestinal wall isolated in different times after the FD4 loaded carriers were intragastrically administrated. Furthermore, the images revealed that TMC-Arg8-Lips could penetrate deeply inside the mucosal membrane. The pharmacodynamic study indicated that TMC-Arg8-Lips containing calcitonin were more efficient in enhancing the absorption and prolonging the reduction of blood calcemia in rats. The area above the plasma calcium concentration-time curve (AAC) of TMC-Arg8-Lips containing calcitonin was increased by more than 16.6- and 1.6-fold when compared to Non-Lips and TMC-Lips, respectively.

  9. Is there an inherent limit to the efficacy of calcitonin gene-related peptide receptor antagonists in the acute treatment of migraine? A comment

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer C

    2009-01-01

    Calcitonin gene-related peptide (CGRP) receptor antagonists are a new treatment principle in acute migraine attacks. Intravenous olcegepant 2.5 mg resulted in 66% headache relief after 2 h, whereas subcutaneous sumatriptan resulted in 81-92% headache relief after 2 h. The intrinsic activity...... antagonism results in success in the acute treatment of migraine in only a certain fraction of the patients....

  10. 离子导入对降钙素经皮促渗作用的研究%Research on the Role of Iontophoresis in Calcitonin Percutaneous Penetration

    Institute of Scientific and Technical Information of China (English)

    王双侠; 魏雅冬; 戴明

    2011-01-01

    To improve biological macromolecules transdennal therapeutic drug concentration, peptide drug salmon calcitonin is taken as a model of biological drugs, the impact of iontophoresis and chemical penetration enhancers on percutaneous penetration of salmon calcitonin is studied. Dualchamber diffusion cells methods are adopted to investigate transdermal penetration effect of iontophoresis, Azone chemical penetration enhancers and iontophoresis - Azone and use of salmon calcitonin.%为了提高大分子生物药经皮给药的治疗浓度,以多肽类生物药鲑降钙素为模型药物,研究离子导入法和化学促渗剂对鲑降钙素经皮渗透的影响:利用水平双室扩散池的方法,考察了离子导入法、化学促渗剂氮酮以及离子导入-氯酮并用对鲑降钙素经皮渗透的促渗作用.

  11. 骨化三醇联合鲑鱼降钙素治疗肾性骨病的临床疗效分析%Therapeutic Analysis of Combination of Calcitriol and Salmon Calcitonin on Renal Osteodystrophy

    Institute of Scientific and Technical Information of China (English)

    陈景; 唐东兴; 张琳; 章可铸

    2014-01-01

    Objective To analyse the clinical efficacy of the calcitriol and salmon calcitonin combination therapy on renal osteodystrophy. Method 30 patients suffered from renal osteodystrophy were treated with calcitriol ( control group, n=15) or calcitriol and salmon calcitonin (CSC group,n=15),respectively. The clinical efficacy,biochemical indicators and adverse reactions were compared. Results Bone pain,joint pain,skin itching and other symptoms after treatment have improved compared with those before treatment. The total clinical effective rate in CSC group was significantly higher than that in the control group (P<0. 05). After treatment,the serum phosphorus and PTH levels were decreased in varying degrees compared with that before treatment and serum calcium levels were elevated (P<0. 05). Indicators of treatment group improved more obviously compared with that in control group (P<0. 05). No adverse effects were found in the two groups during the medication. Conclusion Combination of calcitriol and salmon calcium in treatment of renal osteodys-trophy can effectively alleviate the clinical symptoms,such as bone pain,joint pain,and itchy skin,etc,which is worthy of being recommended.%目的分析骨化三醇和鲑鱼降钙素联合治疗肾性骨病的临床疗效。方法回顾分析2010年1月~2012年12月在本院治疗的肾性骨病患者30例,选择经骨化三醇联合鲑鱼降钙素治疗患者为治疗组,单纯运用骨化三醇治疗的患者为对照组,每组15例。比较两组临床疗效、生化指标改善情况及不良反应发生情况。结果两组患者治疗后骨痛、关节痛、皮肤瘙痒等临床症状均较治疗前有不同程度的改善,联合组患者临床总有效率明显高于对照组(P<0.05)。两组患者治疗后血清磷和PTH水平均较治疗前有不同程度的下降,而血清钙水平较治疗前有不同程度的升高(P<0.05)。两组患者服药期间未发现明显不良反应。结论骨化三醇联合鲑

  12. Serum pneumoproteins in firefighters

    NARCIS (Netherlands)

    Greven, Frans; Krop, Esmeralda; Burger, Nena; Kerstjens, Huib; Heederik, Dick

    2011-01-01

    Serum Clara cell protein (CC16) and surfactant-associated protein A (SP-A) were measured in a cross-sectional study in 402 firefighters. For the population as a whole, no associations were detected between serum pneumoproteins and smoke exposure. SP-A levels were increased in symptomatic subjects ex

  13. Basal ganglia calcification on computed tomography in systemic lupus erythematosus

    Energy Technology Data Exchange (ETDEWEB)

    Nagaoka, Shohei; Tani, Kenji; Ishigatsubo, Yoshiaki and others

    1988-09-01

    The development of basal ganglia calcification was studied in 85 patients with systemic lupus erythematosus (SLE) by computed tomography (CT). Bilateral calcification of the basal ganglia was found to occur in 5 patients (5.9 %) with SLE, but was not seen in patients with rheumatoid arthritis and progressive systemic sclerosis. All were female with a mean age of 42 years (range 29 - 49). The patients with calcification of the basal ganglia had neurological symptoms, such as psychiatric problems (3 cases), grand mal seizures (1 case), CSF abnormalities (2 cases), and EEG changes (4 cases). There were significantly higher incidences of alopecia, cutaneous vasculitis, leukopenia, and thrombocytopenia in the group with calcifications than those in the group with normal CT findings. Circulating immune complexes were detected and LE tests were positive in 2 patients. Endocrinological examination showed no abnormality in any. We suggest that basal ganglia calcification in SLE might be related to cerebral vasculitis.

  14. Multiple superficial basal cell carcinomas (basalomatosis) following cobalt irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Wollenberg, A.; Przybilla, B. [Muenchen Univ. (Germany). Dermatologische Klinik und Poliklinik; Peter, R.U. [Federal Armed Forces Medical Academy, Munich (Germany). Inst. of Radiobiology

    1995-10-01

    Basalomatosis is an uncommon skin condition characterized by the occurrence of multiple basal cell carcinomas. Many cases reported in the literature have been attributed to arsenic treatment in psoriasis patients. We report a patient with basalomatosis caused by cobalt-60 ({sup 60}Co) irradiation. A 55-year-old farmer developed 43 basal cell carcinomas 20 years after treatment of an immuno-blastoma with {sup 60}Co irradiation. All the tumours were located within the radiation fields. Other possible causes of basalomatosis, such as arsenic intoxication and basal cell naevus syndrome, were excluded. The patient`s multiple superficial basal cell carcinomas probably represent a late adverse effect of the {sup 60}Co irradiation. (Author).

  15. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    OpenAIRE

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsych...

  16. Basal Dynamics and Internal Structure of Ice Sheets

    Science.gov (United States)

    Wolovick, Michael J.

    The internal structure of ice sheets reflects the history of flow and deformation experienced by the ice mass. Flow and deformation are controlled by processes occurring within the ice mass and at its boundaries, including surface accumulation or ablation, ice rheology, basal topography, basal sliding, and basal melting or freezing. The internal structure and basal environment of ice sheets is studied with ice-penetrating radar. Recently, radar observations in Greenland and Antarctica have imaged large englacial structures rising from near the bed that deform the overlying stratigraphy into anticlines, synclines, and overturned folds. The mechanisms that may produce these structures include basal freeze-on, travelling slippery patches at the ice base, and rheological contrasts within the ice column. In this thesis, I explore the setting and mechanisms that produce large basal stratigraphic structures inside ice sheets. First, I use radar data to map subglacial hydrologic networks that deliver meltwater uphill towards freeze-on structures in East Antarctica. Next, I use a thermomechanical flowline model to demonstrate that trains of alternating slippery and sticky patches can form underneath ice sheets and travel downstream over time. The disturbances to the ice flow field produced by these travelling patches produce stratigraphic folds resembling the observations. I then examine the overturned folds produced by a single travelling sticky patch using a kinematic flowline model. This model is used to interpret stratigraphic measurements in terms of the dynamic properties of basal slip. Finally, I use a simple local one-dimensional model to estimate the thickness of basal freeze-on that can be produced based on the supply of available meltwater, the thermal boundary conditions, ice sheet geometry, and the ice flow regime.

  17. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma.

    Science.gov (United States)

    Torres, T; Fernandes, I; Costa, V; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  18. Photodynamic therapy as adjunctive therapy for morpheaform basal cell carcinoma

    OpenAIRE

    Torres, T.; I. Fernandes; Costa, V.; Selores, M

    2011-01-01

    The authors decided to evaluate the possible use of methyl-aminolevulinate photodynamic therapy (MAL-PDT) as adjunctive therapy for morpheaform basal cell carcinoma prior to standard surgical excision in order to reduce tumor size and volume and to facilitate surgical treatment. It was observed that MAL-PDT may be an option as an adjunctive therapy prior to standard surgical excision of morpheaform basal cell carcinoma, leading to less invasive surgery.

  19. Reassessing Models of Basal Ganglia Function and Dysfunction

    OpenAIRE

    Nelson, Alexandra B.; Kreitzer, Anatol C.

    2014-01-01

    The basal ganglia are a series of interconnected subcortical nuclei. The function and dysfunction of these nuclei has been studied intensively as it pertains to motor control, but more recently our knowledge of these functions has broadened to include prominent roles in cognition and affective control. This review will summarize historical models of basal ganglia function, findings which have supported or conflicted with these models, and emphasize recent work in animals and humans directly t...

  20. Cognitive-motor interactions of the basal ganglia in development

    OpenAIRE

    Gerry eLeisman; Orit eBraun-Benjamin; Robert eMelillo

    2014-01-01

    Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures and the neocortex throughout the human brain regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia, which regulate motor control, are also crucial elements in the circuits that confer human reasoning and adaptive function. The basal ganglia are key elements in the control of reward-bas...

  1. Basal cell carcinomas in elderly patients treated by cryotherapy.

    Science.gov (United States)

    Chiriac, Anca; Mihaila, Doina; Foia, Liliana; Solovan, Caius

    2013-01-01

    Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain) can be applied and resolve such cases.

  2. An MRI atlas of the mouse basal ganglia.

    Science.gov (United States)

    Ullmann, Jeremy F P; Watson, Charles; Janke, Andrew L; Kurniawan, Nyoman D; Paxinos, George; Reutens, David C

    2014-07-01

    The basal ganglia are a group of subpallial nuclei that play an important role in motor, emotional, and cognitive functions. Morphological changes and disrupted afferent/efferent connections in the basal ganglia have been associated with a variety of neurological disorders including psychiatric and movement disorders. While high-resolution magnetic resonance imaging has been used to characterize changes in brain structure in mouse models of these disorders, no systematic method for segmentation of the C57BL/6 J mouse basal ganglia exists. In this study we have used high-resolution MR images of ex vivo C57BL/6 J mouse brain to create a detailed protocol for segmenting the basal ganglia. We created a three-dimensional minimum deformation atlas, which includes the segmentation of 35 striatal, pallidal, and basal ganglia-related structures. In addition, we provide mean volumes, mean T2 contrast intensities and mean FA and ADC values for each structure. This MR atlas is available for download, and enables researchers to perform automated segmentation in genetic models of basal ganglia disorders.

  3. Preparation and in vivo absorption evaluation of spray dried powders containing salmon calcitonin loaded chitosan nanoparticles for pulmonary delivery

    Directory of Open Access Journals (Sweden)

    Sinsuebpol C

    2013-08-01

    Full Text Available Chutima Sinsuebpol, Jittima Chatchawalsaisin, Poj Kulvanich Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, Thailand Purpose: The aim of the present study was to prepare inhalable co-spray dried powders of salmon calcitonin loaded chitosan nanoparticles (sCT-CS-NPs with mannitol and investigate pulmonary absorption in rats. Methods: The sCT-CS-NPs were prepared by the ionic gelation method using sodium tripolyphosphate (TPP as a cross-linking polyion. Inhalable dry powders were obtained by co-spray drying aqueous dispersion of sCT-CS-NPs and mannitol. sCT-CS-NPs co-spray dried powders were characterized with respect to morphology, particle size, powder density, aerodynamic diameter, protein integrity, in vitro release of sCT, and aerosolization. The plasmatic sCT levels following intratracheal administration of sCT-CS-NPs spray dried powders to the rats was also determined. Results: sCT-CS-NPs were able to be incorporated into mannitol forming inhalable microparticles by the spray drying process. The sCT-CS-NPs/mannitol ratios and spray drying process affected the properties of the microparticles obtained. The conformation of the secondary structures of sCTs was affected by both mannitol content and spray dry inlet temperature. The sCT-CS-NPs were recovered after reconstitution of spray dried powders in an aqueous medium. The sCT release profile from spray dried powders was similar to that from sCT-CS-NPs. In vitro inhalation parameters measured by the Andersen cascade impactor indicated sCT-CS-NPs spray dried powders having promising aerodynamic properties for deposition in the deep lung. Determination of the plasmatic sCT levels following intratracheal administration to rats revealed that the inhalable sCT-CS NPs spray dried powders provided higher protein absorption compared to native sCT powders. Conclusion: The sCT-CS-NPs with mannitol based spray dried powders were

  4. 降钙素基因相关肽受体组分蛋白%Researches of calcitonin gene-related peptide receptor component protein

    Institute of Scientific and Technical Information of China (English)

    唐江琼; 秦旭平

    2011-01-01

    降钙素基因相关肽受体组分蛋白(calcitonin gene-related peptide-receptor component protein,CGRP-RCP)是降钙素基因相关肽受体的一个具有146/148个氨基酸的胞内膜周边蛋白,特异地与降钙素受体样受体(calcitonin receptor-like receptor,CRLR)相互作用并促进CGRP和肾上腺髓质素的信号跨膜转导,现认为CGRP-RCP也是G蛋白偶联受体中一个动态的调节器.CGRP-RCP的mRNA在人和鼠的几乎所有组织均可检测到,在小鼠睾丸中分布尤其明显.在哺乳动物中,CGRP-RCP与C17(酵母菌中聚合酶Ⅲ的必需亚基)是直系同源蛋白,人体的CGRP-RCP能取代酵母中的C17,发挥与Cl7相同的生物学作用.%Calcitonin gene-related peptide receptor component protein (CGRP-RCP), an additional accessory protein of the calcitonin gene-related peptide receptor and an intracellular peripheral membrane protein, is composed of 146-148 residues, which interacts specifically with the calcitonin receptor-like receptor (CRLR) and facilitates signal transduction by CGRP and adrenomedullin.Furthermore, CGRP-RCP is a dynamic regulator of G protein-coupled signal transduction, and implies an additional level of receptor regulation unique to the CGRP system. The CGRP-RCP mRNA is expressed in all tissues of the human and mice, especially more in the testis of mice. Moreover, CGRP-RCP is the mammalian orthologue of C 17 (an essential subunit of yeast RNA polymerase) and human RCP could functionally replace its orthologue in yeast.

  5. Basal physiological parameters in domesticated tree shrews(Tupaia belangeri chinensis)

    Institute of Scientific and Technical Information of China (English)

    Jing WANG; Xin-Li XU; Ze-Yang DING; Rong-Rong MAO; Qi-Xin ZHOU; Long-Bao LV; Li-Ping WANG; Shuang WANG; Chen ZHANG

    2013-01-01

    Establishing non-human primate models of human diseases is an efficient way to narrow the large gap between basic studies and translational medicine.Multifold advantages such as simplicity of breeding,low cost of feeding and facility of operating make the tree shrew an ideal non-human primate model proxy.Additional features like vulnerability to stress and spontaneous diabetic characteristics also indicate that the tree shrew could be a potential new animal model of human diseases.However,basal physiological indexes of tree shrew,especially those related to human disease,have not been systematically reported.Accordingly,we established important basal physiological indexes of domesticated tree shrews including several factors:(1) body weight,(2) core body temperature and rhythm,(3) diet metabolism,(4) locomotor rhythm,(5) electroencephalogram,(6) glycometabolism and (7) serum and urinary hormone level and urinary cortisol rhythm.We compared the physiological parameters of domesticated tree shrew with that of rats and macaques.Results showed that (a) the core body temperature of the tree shrew was 39.59±0.05 ℃,which was higher than that of rats and macaques; (b) Compared with wild tree shrews,with two activity peaks,domesticated tree shrews had only one activity peak from 17:30 to 19:30; (c) Compared with rats,tree shrews had poor carbohydrate metabolism ability; and (d) Urinary cortisol rhythm indicated there were two peaks at 8:00 and 17:00 in domesticated tree shrews,which matched activity peaks in wild tree shrews.These results provided basal physiological indexes for domesticated tree shrews and laid an important foundation for diabetes and stress-related disease models established on tree shrews.

  6. [Serum sickness in diphtheria].

    Science.gov (United States)

    Vozianova, Zh I; Chepilko, K I

    1999-01-01

    As many as 2247 patients with different clinical forms of diphtheria were examined. Antidiphtheric serum (ADS) was administered in 1556 children, the dosage being determined by condition of the patient. Serum sickness developed at day 7 to 9 in 24 (1.5%); 10 patients were found to run a mild course, 14--moderately severe. 6 patients had allergic reactions: 3--to antibiotic (penicillin), urticaria type, 1--to pertussoid-tetanic anatoxin, 2 had pollinosis-type reaction. Thus, serum sickness has practical value, which fact requires a detailed allergic history together with skin tests to be performed before the administration of ADS.

  7. Cognitive-Motor Interactions of the Basal Ganglia in Development

    Directory of Open Access Journals (Sweden)

    Gerry eLeisman

    2014-02-01

    Full Text Available Neural circuits linking activity in anatomically segregated populations of neurons in subcortical structures regulate complex behaviors such as walking, talking, language comprehension, and other cognitive functions associated with frontal lobes. The basal ganglia are also crucial elements in the circuits that confer human reasoning and adaptive function and are key elements in the control of reward-based learning, sequencing, discrete elements that constitute complete motor acts, and cognitive function. Imaging studies of intact humans and electrophysiologic studies of the brains and behavior of other species confirm these findings. We know that the relation between the basal ganglia and the cerebral cortical region allows for connections organized into discrete circuits. Rather than serving as a means for widespread cortical areas to gain access to the motor system, these loops reciprocally interconnect a large and diverse set of cerebral cortical areas with the basal ganglia. Neuronal activity within the basal ganglia associated with motor areas of the cerebral cortex is highly correlated with parameters of movement. Neuronal activity within the basal ganglia and cerebellar loops associated with the prefrontal cortex is related to the aspects of cognitive function. Thus, individual loops appear to be involved in distinct behavioral functions. Damage to the basal ganglia of circuits with motor areas of the cortex leads to motor symptoms, whereas damage to the subcortical components of circuits with non-motor areas of the cortex causes higher-order deficits. In this report, we review some of the anatomic, physiologic, and behavioral findings that have contributed to a reappraisal of function concerning the basal ganglia and cerebellar loops with the cerebral cortex and apply it in clinical applications to ADHD with biomechanics and a discussion of retention of primitive reflexes being highly associated with the condition.

  8. Vismodegib (ERIVEDGE°) In basal cell carcinoma: too many unknowns.

    Science.gov (United States)

    2015-01-01

    Basal cell carcinomas are the most common skin cancers. They are usually localised and carry a good prognosis. There is no standard treatment for the rare patients with metastatic basal cell carcinoma or very extensive basal cell carcinoma for whom surgery or radiotherapy is inappropriate. Vismodegib, a cytotoxic drug, is claimed to prevent tumour growth by inhibiting a pathway involved in tissue repair and embryogenesis. It has been authorised in the European Union for patients with metastatic or locally advanced and extensive basal cell carcinoma. Clinical evaluation of vismodegib is based on a non-comparative clinical trial involving 104 patients, providing only weak evidence. Twenty-one months after the start of the trial, 7 patients with metastases (21%) and 6 patients with advanced basal cell carcinoma (10%) had died. Given the lack of a placebo group, there is no way of knowing whether vismodegib had any effect, positive or negative, on survival. There were no complete responses among patients with metastases, but about one-third of them had partial responses. Among the 63 patients with locally advanced basal cell carcinoma, there were 14 complete responses and 16 partial responses. The recurrence rate in patients with complete responses was not reported. Similar results were reported in two other uncontrolled trials available in mid-2014. Vismodegib has frequent and sometimes serious adverse effects, including muscle spasms, fatigue and severe hyponatraemia. Cases of severe weight loss, alopecia, ocular disorders, other cancers (including squamous cell carcinoma) and anaemia have also been reported. More data are needed on possible hepatic and cardiovascular adverse effects. A potent teratogenic effect was seen in experimental animals. As vismodegib enters semen, contraception is mandatory for both men (condoms) and women. In practice, vismodegib has frequent and varied adverse effects, some of which are serious, while its benefits are poorly documented

  9. A new method to increase selectivity of transglutaminase mediated PEGylation of salmon calcitonin and human growth hormone.

    Science.gov (United States)

    Mero, Anna; Schiavon, Mariano; Veronese, Francesco M; Pasut, Gianfranco

    2011-08-25

    Modification of therapeutic proteins and peptides by polyethylene glycol (PEG) conjugation is a well-known approach to improve the pharmacological properties of drugs. Several chemical procedures of PEG coupling are already in use but an alternative method based on microbial transglutaminase (mTGase) was recently devised. The enzyme catalyzes the link of mPEG-NH(2) to glutamines (Gln) of a substrate protein. In this case the advantage resides in the fact that usually only few Gln(s) in a protein are substrate of mTGase. In order to further restrict the selectivity of the enzyme, we investigated a new approach leading to the formation of a single conjugate isomer as well as for those proteins containing two or more Gln(s) as mTGase substrates. It was found that the addition of co-solvents in the reaction mixture influenced both the secondary structure of the targeted protein and the mTGase activity. The enzymatic PEGylation under these conditions yielded only mono- and selectively modified conjugates. The method was investigated with salmon calcitonin (sCT) and human growth hormone (hGH). In the case of sCT we also demonstrated the importance of site-selective conjugation for the preservation of in vivo activity.

  10. The slowly aggregating salmon Calcitonin: a useful tool for the study of the amyloid oligomers structure and activity.

    Science.gov (United States)

    Diociaiuti, Marco; Gaudiano, Maria Cristina; Malchiodi-Albedi, Fiorella

    2011-01-01

    Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature). In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. In particular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect.

  11. Prolonged Hypocalcemic Effect by Pulmonary Delivery of Calcitonin Loaded Poly(Methyl Vinyl Ether Maleic Acid Bioadhesive Nanoparticles

    Directory of Open Access Journals (Sweden)

    J. Varshosaz

    2014-01-01

    Full Text Available The purpose of the present study was to design a pulmonary controlled release system of salmon calcitonin (sCT. Therefore, poly(methyl vinyl ether maleic acid [P(MVEMA] nanoparticles were prepared by ionic cross-linking method using Fe2+ and Zn2+ ions. Physicochemical properties of nanoparticles were studied in vitro. The stability of sCT in the optimized nanoparticles was studied by electrophoretic gel method. Plasma calcium levels until 48 h were determined in rats as pulmonary-free sCT solution or nanoparticles (25 μg·kg−1, iv solution of sCT (5 μg·kg−1, and pulmonary blank nanoparticles. The drug remained stable during fabrication and tests on nanoparticles. The optimized nanoparticles showed proper physicochemical properties. Normalized reduction of plasma calcium levels was at least 2.76 times higher in pulmonary sCT nanoparticles compared to free solution. The duration of hypocalcemic effect of pulmonary sCT nanoparticles was 24 h, while it was just 1 h for the iv solution. There was not any significant difference between normalized blood calcium levels reduction in pulmonary drug solution and iv injection. Pharmacological activity of nanoparticles after pulmonary delivery was 65% of the iv route. Pulmonary delivery of P(MVEMA nanoparticles of sCT enhanced and prolonged the hypocalcemic effect of the drug significantly.

  12. Noncovalent pegylation by dansyl-poly(ethylene glycol)s as a new means against aggregation of salmon calcitonin.

    Science.gov (United States)

    Mueller, Claudia; Capelle, Martinus A H; Arvinte, Tudor; Seyrek, Emek; Borchard, Gerrit

    2011-05-01

    During all stages of protein drug development, aggregation is one of the most often encountered problems. Covalent conjugation of poly(ethylene glycol) (PEG), also called PEGylation, to proteins has been shown to reduce aggregation of proteins. In this paper, new excipients based on PEG are presented that are able to reduce aggregation of salmon calcitonin (sCT). Several PEG polymers consisting of a hydrophobic dansyl-headgroup attached to PEGs of different molecular weights have been synthesized and characterized physicochemically. After addition of dansyl-methoxypoly(ethylene glycol) (mPEG) 2 kDa to a 40 times molar excess of sCT resulted in an increase in dansyl-fluorescence and a decrease in 90° light scatter suggesting possible interactions. The aggregation of sCT in different buffer systems in presence or absence of the different dansyl-PEGs was measured by changes in Nile red fluorescence and turbidity. Dansyl-mPEG 2 kDa in a 1:1 molar ratio to sCT strongly reduced aggregation. Reduction of sCT aggregation was also measured for the bivalent dansyl-PEG 3 kDa in a 1:1 molar ratio. Dansyl-mPEG 5 kDa deteriorated sCT aggregation. Potential cytotoxicity and hemolysis were investigated. This paper shows that dansyl-PEGs are efficacious in reducing aggregation of sCT.

  13. The Slowly Aggregating Salmon Calcitonin: A Useful Tool for the Study of the Amyloid Oligomers Structure and Activity

    Directory of Open Access Journals (Sweden)

    Marco Diociaiuti

    2011-12-01

    Full Text Available Amyloid proteins of different aminoacidic composition share the tendency to misfold and aggregate in a similar way, following common aggregation steps. The process includes the formation of dimers, trimers, and low molecular weight prefibrillar oligomers, characterized by the typical morphology of globules less than 10 nm diameter. The globules spontaneously form linear or annular structures and, eventually, mature fibers. The rate of this process depends on characteristics intrinsic to the different proteins and to environmental conditions (i.e., pH, ionic strength, solvent composition, temperature. In the case of neurodegenerative diseases, it is now generally agreed that the pathogenic aggregates are not the mature fibrils, but the intermediate, soluble oligomers. However, the molecular mechanism by which these oligomers trigger neuronal damage is still unclear. Inparticular, it is not clear if there is a peculiar structure at the basis of the neurotoxic effect and how this structure interacts with neurons. This review will focus on the results we obtained using salmon Calcitonin, an amyloid protein characterized by a very slow aggregation rate, which allowed us to closely monitor the aggregation process. We used it as a tool to investigate the characteristics of amyloid oligomers formation and their interactions with neuronal cells. Our results indicate that small globules of about 6 nm could be the responsible for the neurotoxic effects. Moreover, our data suggest that the rich content in lipid rafts of neuronal cell plasma membrane may render neurons particularly vulnerable to the amyloid protein toxic effect.

  14. Calcitonin gene-related peptide regulation of glial cell-line derived neurotrophic factor in differentiated rat myotubes.

    Science.gov (United States)

    Rosa, Elyse; Cha, Jieun; Bain, James R; Fahnestock, Margaret

    2015-03-01

    Glial cell-line derived neurotrophic factor (GDNF) is the most potent trophic factor for motoneuron survival and neuromuscular junction formation. GDNF is upregulated in injured or denervated skeletal muscle and returns to normal levels following reinnervation. However, the mechanism by which GDNF is regulated in denervated muscle is not well understood. The nerve-derived neurotransmitter calcitonin gene-related peptide (CGRP) is upregulated following neuromuscular injury and is subsequently released from motoneurons at the neuromuscular junction. CGRP also promotes nerve regeneration, but the mechanism is not well understood. The current study investigates whether this increase in CGRP regulates GDNF, thus playing a key role in promoting regeneration of injured nerves. This study demonstrates that CGRP increases GDNF secretion without affecting its transcription or translation. Rat L6 myoblasts were differentiated into myotubes and subsequently treated with CGRP. GDNF mRNA expression levels were quantified by quantitative real-time reverse transcription-polymerase chain reaction, and secreted GDNF was quantified in the conditioned medium by ELISA. CGRP treatment increased secreted GDNF protein without altering GDNF mRNA levels. The translational inhibitor cycloheximide did not affect CGRP-induced GDNF secreted protein levels, whereas the secretional inhibitor brefeldin A blocked the CGRP-induced increase in GDNF. This study highlights the importance of injury-induced upregulation of CGRP by exposing its ability to increase GDNF levels and demonstrates a secretional mechanism for regulation of this key regeneration-promoting neurotrophic factor.

  15. Statins decrease expression of the proinflammatory neuropeptides calcitonin gene-related peptide and substance P in sensory neurons.

    Science.gov (United States)

    Bucelli, Robert C; Gonsiorek, Eugene A; Kim, Woo-Yang; Bruun, Donald; Rabin, Richard A; Higgins, Dennis; Lein, Pamela J

    2008-03-01

    Clinical and experimental observations suggest that statins may be useful for treating diseases presenting with predominant neurogenic inflammation, but the mechanism(s) mediating this potential therapeutic effect are poorly understood. In this study, we tested the hypothesis that statins act directly on sensory neurons to decrease expression of proinflammatory neuropeptides that trigger neurogenic inflammation, specifically calcitonin gene-related peptide (CGRP) and substance P. Reverse transcriptase-polymerase chain reaction, radioimmunoassay, and immunocytochemistry were used to quantify CGRP and substance P expression in dorsal root ganglia (DRG) harvested from adult male rats and in primary cultures of sensory neurons derived from embryonic rat DRG. Systemic administration of statins at pharmacologically relevant doses significantly reduced CGRP and substance P levels in DRG in vivo. In cultured sensory neurons, statins blocked bone morphogenetic protein (BMP)-induced CGRP and substance P expression and decreased expression of these neuropeptides in sensory neurons pretreated with BMPs. These effects were concentration-dependent and occurred independent of effects on cell survival or axon growth. Statin inhibition of neuropeptide expression was reversed by supplementation with mevalonate and cholesterol, but not isoprenoid precursors. BMPs signal via Smad activation, and cholesterol depletion by statins inhibited Smad1 phosphorylation and nuclear translocation. These findings identify a novel action of statins involving down-regulation of proinflammatory neuropeptide expression in sensory ganglia via cholesterol depletion and decreased Smad1 activation and suggest that statins may be effective in attenuating neurogenic inflammation.

  16. Expression pattern of sonic hedgehog signaling and calcitonin gene-related peptide in the socket healing process after tooth extraction.

    Science.gov (United States)

    Pang, Pai; Shimo, Tsuyoshi; Takada, Hiroyuki; Matsumoto, Kenichi; Yoshioka, Norie; Ibaragi, Soichiro; Sasaki, Akira

    2015-11-06

    Sonic Hedgehog (SHH), a neural development inducer, plays a significant role in the bone healing process. Calcitonin gene-related peptide (CGRP), a neuropeptide marker of sensory nerves, has been demonstrated to affect bone formation. The roles of SHH signaling and CGRP-positive sensory nerves in the alveolar bone formation process have been unknown. Here we examined the expression patterns of SHH signaling and CGRP in mouse socket by immunohistochemistry and immunofluorescence analysis. We found that the expression level of SHH peaked at day 3 and was then decreased at 5 days after tooth extraction. CGRP, PTCH1 and GLI2 were each expressed in a similar pattern with their highest expression levels at day 5 and day 7 after tooth extraction. CGRP and GLI2 were co-expressed in some inflammatory cells and bone forming cells. In some areas, CGRP-positive neurons expressed GLI2. In conclusion, SHH may affect alveolar bone healing by interacting with CGRP-positive sensory neurons and thus regulate the socket's healing process after tooth extraction.

  17. Calcitonin gene-related peptide (CGRP) levels during glyceryl trinitrate (GTN)-induced headache in healthy volunteers.

    Science.gov (United States)

    Kruuse, C; Iversen, H K; Jansen-Olesen, I; Edvinsson, L; Olesen, J

    2010-04-01

    The role of nitric oxide (NO) in migraine has been studied in the experimental glyceryl trinitrate (GTN)-infusion headache model. We hypothesized that GTN-induced headache may activate the trigeminovascular system and be associated with increased levels of sensory neuropeptides, including calcitonin gene-related peptide (CGRP). CGRP, vasoactive intestinal peptide (VIP), neuropeptide Y (NPY) and somatostatin plasma levels were measured before and after placebo/sumatriptan injection and during GTN-induced headache. Following a double-blind randomized cross-over design, 10 healthy volunteers received subcutaneous sumatriptan 6 mg or placebo. This was succeeded by 20 min of GTN (0.12 µg kg(-1) min(-1)) infusion. At baseline no subject reported headache (using verbal rating scale from 0 to 10) and the jugular CGRP-like immunoreactivity (-LI) level was 18.6 ± 2.5 pmol/l. After a 20-min intravenous infusion of GTN 0.12 µg kg(-1) min(-1), median peak headache intensity was 4 (range 2-6) (P 0.05). There were no changes in VIP-, NPY- or somatostatin-LI. In conclusion, the NO donor GTN appears not to induce headache via immediate CGRP release.

  18. Serum YKL-40

    DEFF Research Database (Denmark)

    Mylin, Anne K; Abildgaard, Niels; Johansen, Julia S

    2015-01-01

    In a time of increasing treatment options for multiple myeloma bone disease, risk factors predicting progression need to be elucidated. This study investigated the value of serum YKL-40, previously shown to be associated with radiographic progression of bone destruction, as a predictor for time...... for SRE and at 9 and 24 months for radiographic progression. Elevated serum YKL-40 was seen in 47% of patients and associated with high-risk disease (International Staging System stage III; p serum CTX/MMP; p ... to clinical progression, i.e. skeletal-related events (SREs), in 230 newly diagnosed patients with multiple myeloma receiving intravenous bisphosphonates. Serum concentrations of YKL-40 and biochemical bone markers (CTX-MMP, CTX-I, PINP) were measured at diagnosis. Patients were evaluated every third month...

  19. Toward sophisiticated basal ganglia neuromodulation: review on basal gaglia deep brain stimulation

    Science.gov (United States)

    Da Cunha, Claudio; Boschen, Suelen L.; Gómez-A, Alexander; Ross, Erika K.; Gibson, William S. J.; Min, Hoon-Ki; Lee, Kendall H.; Blaha, Charles D.

    2015-01-01

    This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson’s disease, Huntington’s disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases. Emphasis is given to the role of striatal dopamine on motor performance, motivated behaviors and learning of procedural memories. Next, the use of cutting-edge electrochemical techniques in animal and human studies of BG functioning under normal and disease conditions is discussed. Finally, functional neuroimaging studies are reviewed; these works have shown the relationship between cortico-BG structures activated during DBS and improvement of disease symptoms. PMID:25684727

  20. Resolving basal ganglia calcification in hereditary hypomagnesemia with secondary hypocalcemia due to a novel TRMP6 gene mutation

    Directory of Open Access Journals (Sweden)

    Abdelhadi M Habeb

    2012-01-01

    Full Text Available Hereditary hypomagnesemia with secondary hypocalcemia (HSH is a rare condi-tion caused by mutations in the Transient Receptor Potential Melastatin 6 (TRMP6 gene. Patients usually present during early infancy with symptomatic hypocalcemia; however, intracranial calcification has not been previously reported in HSH. We report on a three-month-old Saudi girl who presented with hypocalcemic convulsions and was initially treated as nutritional rickets. However, further biochemical analysis of blood and urine were suggestive of HSH. This diagnosis was confirmed by mutation analysis, which identified a novel homozygous frame shift mutation (ins 2999T of the TRMP6 gene. A computed tomography brain scan, done around the time of diagnosis, identified bilateral basal ganglia calcification (BGC. Her serum calcium and the BGC improved with magnesium replacement. BGC can be added as a new feature of HSH and the case highlights the importance of measuring serum Mg in patients with hypocalcemic convulsions, particularly in children of consanguineous parents.

  1. Localisation and neural control of the release of calcitonin gene-related peptide (CGRP) from the isolated perfused porcine ileum

    DEFF Research Database (Denmark)

    Rasmussen, T N; Schmidt, P; Poulsen, S S

    2001-01-01

    extracts, CGRP-LI corresponded entirely to porcine CGRP plus smaller amounts of oxidised CGRP. Using isolated vascularly perfused segments of the ileum, we studied the release of CGRP-LI in response to electrical stimulation of the mixed extrinsic periarterial nerves and to infusion of different...... neuroblockers. In addition, the effect of infusion of capsaicin was studied. The basal output of CGRP-LI was 2.9+/-0.7 pmol/5 min (mean+/-S.D.). Electrical nerve stimulation (8 Hz) significantly increased the release of CGRP-LI to 167+/-16% (mean+/-S.E.M.) of the basal output (n=13). This response...

  2. Basal cell carcinomas in elderly patients treated by cryotherapy

    Directory of Open Access Journals (Sweden)

    Chiriac A

    2013-03-01

    Full Text Available Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face in elderly patients. We present three cases of basal cell carcinoma with good results with cryotherapy. This report aims to outline and to prove that in some difficult situations, a simple, inexpensive, easy-to-perform procedure with no contraindications and with minimal side effects (erythema, mild pain can be applied and resolve such cases. Keywords: basal cell carcinoma, cryotherapy

  3. An Unusual Location of Basal Cell Carcinoma: Two Case Reports

    Directory of Open Access Journals (Sweden)

    Birgül Tepe

    2012-06-01

    Full Text Available Basal cell carcinoma is the most common malignant skin tumour. Chronic sun exposure is considered as the main etiologic factor in its development. Although it mainly occurs on sun-exposed areas as the face and neck, it rarely develops on the forearms and/or arms. The etiologic factors which affect the anatomic distribution of basal cell carcinoma are not well-known. Here we report two patients who developed basal cell carcinoma on the forearm. None of the patients had a specific etiologic factor except for chronic sunlight exposure. The aim of our report is to show that this prevalant cutaneous malignancy can be encountered in rare/unusual areas. (Turk J Dermatol 2012; 6: 51-4

  4. Multiple jaw cysts not associated with basal cell nevus syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Suk Ja; Kang, Byung Cheol [Chonnam National University College of Medicine, Kwangju (Korea, Republic of)

    2003-09-15

    We present two cases of multiple jaw cysts not associated with basal cell nevus syndrome. Case 1 : a nine year-old boy visited CNU Hospital for orthodontic treatment and his radiographs showed cystic lesions surrounding the crowns of teeth 13 and 17 respectively, which were diagnosed as dentigerous cysts. Subsequently, two more cysts were found on his follow-up radiographs in 12 and 15 months. The two cysts were determined to be odontogenic keratocysts. The boy had no skeletal abnormalities and no skin lesions associated with basal cell nevus syndrome. Case 2: a fifty-eight year old man had three impacted third molars with pericoronal radiolucencies, which were diagnosed as dentigerous cysts. He had no additional abnormalities associated with basal cell nevus syndrome. Multiple jaw cysts can occur at any age, and periodic radiographic surveillance may be needed for any cases of impacted tooth.

  5. Computed tomography of granulomatous basal meningitis caused by pneumococcus

    Energy Technology Data Exchange (ETDEWEB)

    Sonobe, Makoto; Takahashi, Shinichiro (Mito National Hospital, Ibaraki (Japan)); Ohara, Kazuo

    1983-07-01

    A case of 3-month-old female with ''granulomatous basal meningitis'' caused by pneumococcus was described. She suffered from high fever, vomiting, convulsion and loss of consciousness on January 28th, 1982. On admission the protein content of the spinal fluid was 280 mg/100 ml, the glucose 4 mg/100 ml and the cell count was 1206/3(L : 845, N : 361). Her symptoms and signs were deteriorated in spite of antibiotics and anticonvulsants. CT scan on the 10th day showed the enhanced basal cistern. She died on the 11th day but autopsy was not carried out. In this case, pneumococcus was cultured in CSF. This seemed to be the first case of ''granulomatous basal meningitis'' due to purulent meningitis in Japan.

  6. Effect of Crossing C57BL/6 and FVB Mouse Strains on Basal Cytokine Expression

    Directory of Open Access Journals (Sweden)

    Agata Szade

    2015-01-01

    Full Text Available C57BL/6 is the most often used laboratory mouse strain. However, sometimes it is beneficial to cross the transgenic mice on the C57BL/6 background to the other strain, such as FVB. Although this is a common strategy, the influence of crossing these different strains on homeostatic expression of cytokines is not known. Here we have investigated the differences in the expression of selected cytokines between C57BL/6J and C57BL/6JxFVB mice in serum and skeletal muscle. We have found that only few cytokines were altered by crossing of the strains. Concentrations of IL5, IL7, LIF, MIP-2, and IP-10 were higher in serum of C57BL/6J mice than in C57BL/6JxFVB mice, whereas concentration of G-CSF was lower in C57BL/6J. In the skeletal muscle only the concentration of VEGF was higher in C57BL/6J mice than in C57BL/6JxFVB mice. Concluding, the differences in cytokine expression upon crossing C57BL/6 and FVB strain in basal conditions are not profound.

  7. Kinome expression profiling and prognosis of basal breast cancers

    Directory of Open Access Journals (Sweden)

    Jacquemier Jocelyne

    2011-07-01

    Full Text Available Abstract Background Basal breast cancers (BCs represent ~15% of BCs. Although overall poor, prognosis is heterogeneous. Identification of good- versus poor-prognosis patients is difficult or impossible using the standard histoclinical features and the recently defined prognostic gene expression signatures (GES. Kinases are often activated or overexpressed in cancers, and constitute targets for successful therapies. We sought to define a prognostic model of basal BCs based on kinome expression profiling. Methods DNA microarray-based gene expression and histoclinical data of 2515 early BCs from thirteen datasets were collected. We searched for a kinome-based GES associated with disease-free survival (DFS in basal BCs of the learning set using a metagene-based approach. The signature was then tested in basal tumors of the independent validation set. Results A total of 591 samples were basal. We identified a 28-kinase metagene associated with DFS in the learning set (N = 73. This metagene was associated with immune response and particularly cytotoxic T-cell response. On multivariate analysis, a metagene-based predictor outperformed the classical prognostic factors, both in the learning and the validation (N = 518 sets, independently of the lymphocyte infiltrate. In the validation set, patients whose tumors overexpressed the metagene had a 78% 5-year DFS versus 54% for other patients (p = 1.62E-4, log-rank test. Conclusions Based on kinome expression, we identified a predictor that separated basal BCs into two subgroups of different prognosis. Tumors associated with higher activation of cytotoxic tumor-infiltrative lymphocytes harbored a better prognosis. Such classification should help tailor the treatment and develop new therapies based on immune response manipulation.

  8. Molecular characterization of Italian nevoid basal cell carcinoma syndrome patients.

    Science.gov (United States)

    Pastorino, L; Cusano, R; Nasti, S; Faravelli, F; Forzano, F; Baldo, C; Barile, M; Gliori, S; Muggianu, M; Ghigliotti, G; Lacaita, M G; Lo Muzio, L; Bianchi-Scarra, G

    2005-03-01

    Mutations in the PTCH gene, the human homolog of the Drosophila patched gene, have been found to lead to the autosomal dominant disorder termed Nevoid Basal Cell Carcinoma Syndrome (NBCCS, also called Gorlin Syndrome). Patients display an array of developmental anomalies and are prone to develop a variety of tumors, with multiple Basal Cell Carcinomas occurring frequently. We provide here the results of molecular testing of a set of Italian Nevoid Basal Cell Carcinoma Syndrome patients. Twelve familial patients belonging to 7 kindreds and 5 unaffected family members, 6 non-familial patients and an additional set of 7 patients with multiple Basal Cell Carcinoma but no other criteria for the disease were examined for mutations in the PTCH gene. All of the Nevoid Basal Cell Carcinoma Syndrome patients were found to carry variants of the PTCH gene. We detected nine novel mutations (1 of which occurring twice): 1 missense mutation (c.1436T>G [p.L479R]), 1 nonsense mutation (c.1138G>T [p.E380X]), 6 frameshift mutations (c.323_324ins2, c.2011_2012dup, c.2535_2536dup, c.2577_2583del, c.3000_3005del, c.3050_3051del), 1 novel splicing variant (c.6552A>T) and 3 mutations that have been previously reported (c.3168+5G>A, c.1526G>T [p.G509V], and c.3499G>A [p.G1167R]). None of the patients with multiple Basal Cell Carcinoma but no other criteria for the syndrome, carried germline coding region mutations.

  9. A review of stand basal area growth models

    Institute of Scientific and Technical Information of China (English)

    Sun Hong-gang; Zhang Jian-guo; Duan Ai-guo; He Cai-yun

    2007-01-01

    Growth and yield modeling has a long history in forestry. The methods of measuring the growth of stand basal area have evolved from those developed in the U.S.A. and Germany during the last century. Stand basal area modeling has progressed rapidly since the first widely used model was published by the U.S. Forest Service. Over the years, a variety of models have been developed for predicting the growth and yield of uneven/even-aged stands using stand-level approaches. The modeling methodology has not only moved from an empirical approach to a more ecological process-based approach but also accommodated a variety of techniques such as: 1) simultaneous equation methods, 2) difference models, 3) artificial neural network techniques, 4) linear/nonlinear regression models, and 5) matrix models. Empirical models using statistical methods were developed to reproduce accurately and precisely field observations. In contrast, process models have a shorter history, developed originally as research and education tools with the aim of increasing the understanding of cause and effect relationships. Empirical and process models can be married into hybrid models in which the shortcomings of both component approaches can, to some extent, be overcome. Algebraic difference forms of stand basal area models which consist of stand age, stand density and site quality can fully describe stand growth dynamics. This paper reviews the current literature regarding stand basal area models, discusses the basic types of models and their merits and outlines recent progress in modeling growth and dynamics of stand basal area. Future trends involving algebraic difference forms, good fitting variables and model types into stand basal area modeling strategies are discussed.

  10. Nevoid Basal Cell Carcinoma Syndrome : A Case Report

    Directory of Open Access Journals (Sweden)

    K Rajanikanth

    2004-01-01

    Full Text Available The nevoid basal cell carcinoma syndrome (NBCCS or Gorlin - Goltz syndrome is an autosomal disorder principally characterized by cutaneous basal cell carcinomas, multiple keratocysts, and skeletal anomalies. The major organ systems involved are skin, bones, central nervous system, eyes, gonads and endocrine. This particular syndrome is extensively described in the literature under different names. However, there are only few cases reported in the Indian literature. An unusual case of a 33-year old male with large odontogenic keratocyst involving impacted canine in the mandible, along with multiple cysts and impacted teeth in the maxilla; bifid rib and vertebral anomalies has been described.

  11. Immature osteoblastic MG63 cells possess two calcitonin gene-related peptide receptor subtypes that respond differently to [Cys(Acm)(2,7)] calcitonin gene-related peptide and CGRP(8-37).

    Science.gov (United States)

    Kawase, Tomoyuki; Okuda, Kazuhiro; Burns, Douglas M

    2005-10-01

    Calcitonin gene-related peptide (CGRP) is clearly an anabolic factor in skeletal tissue, but the distribution of CGRP receptor (CGRPR) subtypes in osteoblastic cells is poorly understood. We previously demonstrated that the CGRPR expressed in osteoblastic MG63 cells does not match exactly the known characteristics of the classic subtype 1 receptor (CGRPR1). The aim of the present study was to further characterize the MG63 CGRPR using a selective agonist of the putative CGRPR2, [Cys(Acm)(2,7)]CGRP, and a relatively specific antagonist of CGRPR1, CGRP(8-37). [Cys(Acm)(2,7)]CGRP acted as a significant agonist only upon ERK dephosphorylation, whereas this analog effectively antagonized CGRP-induced cAMP production and phosphorylation of cAMP response element-binding protein (CREB) and p38 MAPK. Although it had no agonistic action when used alone, CGRP(8-37) potently blocked CGRP actions on cAMP, CREB, and p38 MAPK but had less of an effect on ERK. Schild plot analysis of the latter data revealed that the apparent pA2 value for ERK is clearly distinguishable from those of the other three plots as judged using the 95% confidence intervals. Additional assays using 3-isobutyl-1-methylxanthine or the PKA inhibitor N-(2-[p-bromocinnamylamino]ethyl)-5-isoquinolinesulfonamide hydrochloride (H-89) indicated that the cAMP-dependent pathway was predominantly responsible for CREB phosphorylation, partially involved in ERK dephosphorylation, and not involved in p38 MAPK phosphorylation. Considering previous data from Scatchard analysis of [125I]CGRP binding in connection with these results, these findings suggest that MG63 cells possess two functionally distinct CGRPR subtypes that show almost identical affinity for CGRP but different sensitivity to CGRP analogs: one is best characterized as a variation of CGRPR1, and the second may be a novel variant of CGRPR2.

  12. Metastatic basal cell carcinoma caused by carcinoma misdiagnosed as acne - case report and literature review

    DEFF Research Database (Denmark)

    Aydin, Dogu; Hölmich, Lisbet Rosenkrantz; Jakobsen, Linda P

    2016-01-01

    Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis.......Basal cell carcinoma can be misdiagnosed as acne; thus, carcinoma should be considered in treatment-resistant acne. Although rare, neglected basal cell carcinoma increases the risk of metastasis....

  13. NMR investigations of structural and dynamics features of natively unstructured drug peptide - salmon calcitonin: implication to rational design of potent sCT analogs.

    Science.gov (United States)

    Rawat, Atul; Kumar, Dinesh

    2013-01-01

    Backbone dynamics and conformational properties of drug peptide salmon calcitonin have been studied in aqueous solution using nuclear magnetic resonance (NMR). Although salmon calcitonin (sCT) is largely unfolded in solution (as has been reported in several circular dichroism studies), the secondary H(α) chemical shifts and three bond H(N) -H(α) coupling constants indicated that most of the residues of the peptide are populating the α-helical region of the Ramachandran (ϕ, ψ) map. Further, the peptide in solution has been found to exhibit multiple conformational states exchanging slowly on the NMR timescale (10(2) -10(3)  s(-1) ), inferred by the multiple chemical shift assignments in the region Leu4-Leu12 and around Pro23 (for residues Gln20-Tyr22 and Arg24). Possibly, these slowly exchanging multiple conformational states might inhibit symmetric self-association of the peptide and, in part, may account for its reduced aggregation propensity compared with human calcitonin (which lacks this property). The (15) N NMR-relaxation data revealed (i) the presence of slow (microsecond-to-millisecond) timescale dynamics in the N-terminal region (Cys1-Ser5) and core residues His17 and Asn26 and (ii) the presence of high frequency (nanosecond-to-picosecond) motions in the C-terminal arm. Put together, the various results suggested that (i) the flexible C-terminal of sCT (from Thr25-Thr31) is involved in identification of specific target receptors, (ii) whereas the N-terminal of sCT (from Cys1-Gln20) in solution - exhibiting significant amount of conformational plasticity and strong bias towards biologically active α-helical structure - facilitates favorable conformational adaptations while interacting with the intermembrane domains of these target receptors. Thus, we believe that the structural and dynamics features of sCT presented here will be useful guiding attributes for the rational design of biologically active sCT analogs.

  14. 鲑鱼降钙素致不良反应的文献分析%A Literature Analysis of Adverse Drug Reactions Induced by Salmon Calcitonin

    Institute of Scientific and Technical Information of China (English)

    苏娜; 吴逢波; 徐珽

    2013-01-01

    Objective To study the characteristics and the general pattern of the adverse drug reaction (ADR) induced by salmon calcitonin. Methods ADR induced by salmon calcitonin reported in domestic medical journals during January 1994 to March 2012 were retrieved from CNKI and WanFang databases. Classification and statistical analysis were carried out according to patients' age, gender, route of administration, dosage, time of the occurrence of ADR, clinical symptoms, allergic history, treatment and recovery. Results Fifteen ADR cases involved the integumentary system , cardiovascular system, digestive system, nervous system and allergic reaction, with advanced age group and women showing the highest incidence. Conclusion Salmon calcitonin should be used with caution in the clinic for it may induce ADR.%目的 总结鲑鱼降钙素致不良反应的一般规律和特点.方法 检索中国期刊全文数据库(CNKI)、万方数据库(WanFang)1994年1月-2012年3月鲑鱼降钙素所致不良反应的个案报道,按患者年龄、性别、给药途径、用药剂量、不良反应发生时间、临床表现症状、有无过敏史、治疗与转归等进行分类统计分析.结果 15例不良反应包括皮肤系统、心血管系统、消化系统、神经系统和超敏反应,高年龄段和女性发生率较高.结论 临床上应重视鲑鱼降钙素可致不良反应,坚持合理用药.

  15. Role in diuresis of a calcitonin receptor (GPRCAL1 expressed in a distal-proximal gradient in renal organs of the mosquito Aedes aegypti (L..

    Directory of Open Access Journals (Sweden)

    Hyeogsun Kwon

    Full Text Available Evolution of anthropophilic hematophagy in insects resulted in the coordination of various physiological processes for survival. In female mosquitoes, a large blood meal provides proteins for egg production and as a trade-off, rapid elimination of the excess water and solutes (Na(+, Cl(- is critical for maintaining homeostasis and removing excess weight to resume flight and avoid predation. This post-prandial excretion is achieved by the concerted action of multiple hormones. Diuresis and natriuresis elicited by the calcitonin-like diuretic hormone 31 (DH(31 are believed to be mediated by a yet uncharacterized calcitonin receptor (GPRCAL in the mosquito Malpighian tubules (MTs, the renal organs. To contribute knowledge on endocrinology of mosquito diuresis we cloned GPRCAL1 from MT cDNA. This receptor is the ortholog of the DH(31 receptor from Drosophila melanogaster that is expressed in principal cells of the fruit fly MT. Immunofluorescence similarly showed AaegGPRCAL1 is present in MT principal cells in A. aegypti, however, exhibiting an overall gradient-like pattern along the tubule novel for a GPCR in insects. Variegated, cell-specific receptor expression revealed a subpopulation of otherwise phenotypically similar principal cells. To investigate the receptor contribution to fluid elimination, RNAi was followed by urine measurement assays. In vitro, MTs from females that underwent AaegGPRcal1 knock-down exhibited up to 57% decrease in the rate of fluid secretion in response to DH(31. Live females treated with AaegGPRcal1 dsRNA exhibited 30% reduction in fluid excreted after a blood meal. The RNAi-induced phenotype demonstrates the critical contribution of this single secretin-like family B GPCR to fluid excretion in invertebrates and highlights its relevance for the blood feeding adaptation. Our results with the mosquito AaegGPRCAL1 imply that the regulatory function of calcitonin-like receptors for ion and fluid transport in renal organs

  16. Role in diuresis of a calcitonin receptor (GPRCAL1) expressed in a distal-proximal gradient in renal organs of the mosquito Aedes aegypti (L.).

    Science.gov (United States)

    Kwon, Hyeogsun; Lu, Hsiao-Ling; Longnecker, Michael T; Pietrantonio, Patricia V

    2012-01-01

    Evolution of anthropophilic hematophagy in insects resulted in the coordination of various physiological processes for survival. In female mosquitoes, a large blood meal provides proteins for egg production and as a trade-off, rapid elimination of the excess water and solutes (Na(+), Cl(-)) is critical for maintaining homeostasis and removing excess weight to resume flight and avoid predation. This post-prandial excretion is achieved by the concerted action of multiple hormones. Diuresis and natriuresis elicited by the calcitonin-like diuretic hormone 31 (DH(31)) are believed to be mediated by a yet uncharacterized calcitonin receptor (GPRCAL) in the mosquito Malpighian tubules (MTs), the renal organs. To contribute knowledge on endocrinology of mosquito diuresis we cloned GPRCAL1 from MT cDNA. This receptor is the ortholog of the DH(31) receptor from Drosophila melanogaster that is expressed in principal cells of the fruit fly MT. Immunofluorescence similarly showed AaegGPRCAL1 is present in MT principal cells in A. aegypti, however, exhibiting an overall gradient-like pattern along the tubule novel for a GPCR in insects. Variegated, cell-specific receptor expression revealed a subpopulation of otherwise phenotypically similar principal cells. To investigate the receptor contribution to fluid elimination, RNAi was followed by urine measurement assays. In vitro, MTs from females that underwent AaegGPRcal1 knock-down exhibited up to 57% decrease in the rate of fluid secretion in response to DH(31). Live females treated with AaegGPRcal1 dsRNA exhibited 30% reduction in fluid excreted after a blood meal. The RNAi-induced phenotype demonstrates the critical contribution of this single secretin-like family B GPCR to fluid excretion in invertebrates and highlights its relevance for the blood feeding adaptation. Our results with the mosquito AaegGPRCAL1 imply that the regulatory function of calcitonin-like receptors for ion and fluid transport in renal organs arose early

  17. Analysis the effect of salmon calcitonin combined with azole phosphonic acid in the treatment of osteoporosis in elderly men%鲑鱼降钙素联合唑来膦酸治疗老年男性骨质疏松症的效果分析

    Institute of Scientific and Technical Information of China (English)

    冯缨缨; 钟远; 金俊

    2015-01-01

    ObjectiveTo explore the effect of salmon calcitonin combined with azole phosphonic acid in the treatment of osteoporosis in elderly men.Method173 cases of elderly male patients with osteoporosis were randomly divided into control group and experimental group, the two groups of patients were given oral calcium supplements, on the basis of the control group patients were given salmon calcitonin nasal spray, experimental group patients were given azole phosphonic acid injection, a course of 1 year. Compared the two groups of patients with clinical efifcacy, bone mineral density (BMD) before and after treatment, serum bone alkaline phosphatase (BAP), serum the C-terminal peptide (CTX) type I collagen levels and adverse reactions.ResultThere was no signiifcant difference of BMD between the two groups before treatment (P>0.05); BMD in both groups after treatment were higher than before treatment (P0.05).ConclusionSalmon calcitonin combined with azole phosphonic acid can effectively improve the elderly male patients with osteoporosis bone mineral density, curative effect is distinct, worth of clinical promotion.%目的:探究鲑鱼降钙素联合唑来膦酸治疗老年男性骨质疏松症的临床效果。方法将本院收治的173例老年男性骨质疏松症患者随机分为对照组及试验组,两组患者均给予口服钙补充剂,在此基础上对照组患者予以鲑鱼降钙素鼻喷剂,试验组患者予以唑来膦酸注射液,疗程均为1年。比较两组患者临床疗效,治疗前后骨密度(BMD),血清骨碱性磷酸酶(BAP)、血清I型胶原C端肽(CTX)水平及不良反应发生情况。结果两组患者治疗前BMD比较差异无显著性(P>0.05);治疗后两组患者BMD均高于治疗前(P<0.05),试验组明显高于对照组(P<0.05)。试验组患者治疗总有效率明显高于对照组(P<0.05)。两组患者治疗后BAP水平均较治疗前升高,CTX水

  18. 鲑鱼降钙素联合低钙透析液治疗血透患者高磷血症的临床研究%Clinical study of low calcium dialysate combined with salmon calcitonin in the treatment of hyperphosphatemia in hemodialysis patients

    Institute of Scientific and Technical Information of China (English)

    关毅标

    2014-01-01

    Objective To evaluate the effect of low calcium dialysate combined with salmon calcitonin in the treatment of hyper-phosphatemia in hemodialysis patients.Methods Forty hemodialysis patients with hyperphosphaemia were randomly divided into the treatment group (n=19) and the control group (n=21).Patients in the control group were treated with low calcium dialysate (with Ca+ concentration of 1.5 mmo1 )combined with calcium carbonate as well as vitamin D3 ,while those in the treatment group were treated with low calcium dialysate (with Ca2+ concentration of 1.25 mmo1)combined with salmon calcitonin,as well as calcium carbonate and vitamin D3.The Ca,phosphate product and iPTH were detected three and six months after treatment.Results In the control group, the serum phosphate and iPTH was significantly increased after treatment ( P0.05). Conclusion For hemodialysis patients with hyperphosphatemia ,low calcium dialysate combined with salmon calcitonin can effectively reduce serum phosphate level with no effect on iPTH.%目的:探讨低钙透析液联合鲑鱼降钙素对维持血透(Maintenance hemodialysis, MHD)患者高磷血症的影响。方法选取我院近期维持性血液透析患者中高磷血症患者40例,采用随机数字表法分为对照组21例,给予常规钙透析液+活性维生素D3治疗;试验组19例,给予低钙透析液联合鲑鱼降钙素注射液治疗。观察两组患者治疗后第3、6个月时血清钙磷代谢等指标有无差别。结果对照组治疗后血清钙较治疗前无明显变化(P>0.05),但血磷和甲状旁腺激素(iPTH)较透析前明显增加(P<0.05);试验组治疗后血清钙、iPTH无明显变化(P>0.05),血磷显著降低(P<0.05)。结论鲑鱼降钙素联合低钙透析液治疗MHD能有效降低患者血磷水平且不致影响iPTH。

  19. Chronic hypoxia increases TRPC6 expression and basal intracellular Ca2+ concentration in rat distal pulmonary venous smooth muscle.

    Directory of Open Access Journals (Sweden)

    Lei Xu

    Full Text Available Hypoxia causes remodeling and contractile responses in both pulmonary artery (PA and pulmonary vein (PV. Here we explore the effect of hypoxia on PV and pulmonary venous smooth muscle cells (PVSMCs.Chronic hypoxic pulmonary hypertension (CHPH model was established by exposing rats to 10% O2 for 21 days. Rat distal PVSMCs were isolated and cultured for in vitro experiments. The fura-2 based fluorescence calcium imaging was used to measure the basal intracellular Ca2+ concentration ([Ca2+]i and store-operated Ca2+ entry (SOCE. Quantitative RT-PCR and western blotting were performed to measure the expression of mRNA and levels of canonical transient receptor potential (TRPC protein respectively.Hypoxia increased the basal [Ca2+]i and SOCE in both freshly dissociated and serum cultured distal PVSMCs. Moreover, hypoxia increased TRPC6 expression at mRNA and protein levels in both cultured PVSMCs exposed to prolonged hypoxia (4% O2, 60 h and distal PV isolated from CHPH rats. Hypoxia also enhanced proliferation and migration of rat distal PVSMCs.Hypoxia induces elevation of SOCE in distal PVSMCs, leading to enhancement of basal [Ca2+]i in PVSMCs. This enhancement is potentially correlated with the increased expression of TRPC6. Hypoxia triggered intracellular calcium contributes to promoted proliferation and migration of PVSMCs.

  20. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik; Møller, Søren; Schifter, S

    2001-01-01

    catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; padrenaline levels (r=-0.......001) and central circulation time (r=-0.49; padrenaline (-16%; p... to COMP(art) disappeared. The relation of COMP(art) to CGRP and circulatory variables remained unchanged. CONCLUSION: Elevated arterial compliance in cirrhosis is related to low adrenaline, high CGRP, and systemic hyperdynamics but not to indicators of the activated vasoconstrictor systems (noradrenaline...

  1. Localization of large conductance calcium-activated potassium channels and their effect on calcitonin gene-related peptide release in the rat trigemino-neuronal pathway

    DEFF Research Database (Denmark)

    Wulf-Johansson, H.; Amrutkar, D.V.; Hay-Schmidt, Anders;

    2010-01-01

    pathophysiology. Here we study the expression and localization of BK(Ca) channels and CGRP in the rat trigeminal ganglion (TG) and the trigeminal nucleus caudalis (TNC) as these structures are involved in migraine pain. Also the effect of the BK(Ca) channel blocker iberiotoxin and the BK(Ca) channel opener NS......Large conductance calcium-activated potassium (BK(Ca)) channels are membrane proteins contributing to electrical propagation through neurons. Calcitonin gene-related peptide (CGRP) is a neuropeptide found in the trigeminovascular system (TGVS). Both BK(Ca) channels and CGRP are involved in migraine...

  2. High arterial compliance in cirrhosis is related to low adrenaline and elevated circulating calcitonin gene related peptide but not to activated vasoconstrictor systems

    DEFF Research Database (Denmark)

    Henriksen, Jens Henrik Sahl; Møller, S; Schifter, S;

    2001-01-01

    , vasoactivity was manipulated by inhalation of oxygen. STUDY POPULATION AND METHODS: In 20 patients with alcoholic cirrhosis and 12 controls we determined COMP(art) (stroke volume relative to pulse pressure), cardiac output, plasma volume, systemic vascular resistance, central circulation time, plasma...... catecholamines, renin activity, endothelin-1, and calcitonin gene related peptide (CGRP) at baseline and during oxygen inhalation. RESULTS: COMP(art) was significantly increased in cirrhotic patients compared with controls (1.32 v 1.06 ml/mm Hg; p

  3. Calcitonin gene-related peptide in medullary thyroid carcinomas: characterization of molecular forms including the amidated C-terminus.

    Science.gov (United States)

    Schifter, S; Johnsen, A H

    1994-01-01

    CGRP was extracted from three familial and four sporadic medullary thyroid carcinomas (MTC) and was measured by an assay specific for the amidated C-terminus. The antibody showed equal affinity for alpha- and beta-CGRP. All tumors contained high concentrations of CGRP (range: 63-7889 pmol/g) compared to spinal cord (86 pmol/g), thyroid gland (4 pmol/g), and two small-cell lung carcinomas (4 and 1 pmol/g, respectively). The concentration of calcitonin (CT) was determined with an assay specific for an epitope involving the midportion and C-terminal end of the molecule. In six of the seven tumors investigated, concentrations of CT were found to be higher than for CGRP. Gel chromatography showed heterogeneity with respect to CGRP immunoreactivity. Thus, in all seven extracts, three peaks were seen with Kd values 0.37, 0.63, and 0.80, respectively. This profile of immunoreactive CGRP was similar to that obtained from human medulla spinalis, thereby indicating normal posttranslational processing of pro-CGRP in MTC tumors. Further characterization of the three main peaks identified by gel chromatography was performed on pooled fractions from one of the tumors using HPLC, sequencing, and mass spectrometry. The immunoreactive peak with Kd 0.37 was identified as human beta-CGRP, the peak with Kd 0.63 as 19-37 beta-CGRP, and the peak with Kd 0.80 as 25-37 beta-CGRP. No alpha-CGRP was identified in this tumor. This indicates selective expression of beta-CGRP, at least in the tumor investigated.

  4. Tryptophan-mPEGs: novel excipients that stabilize salmon calcitonin against aggregation by non-covalent PEGylation.

    Science.gov (United States)

    Mueller, Claudia; Capelle, Martinus A H; Arvinte, Tudor; Seyrek, Emek; Borchard, Gerrit

    2011-11-01

    Protein aggregation, which is triggered by various factors, is still one of the most prevalent problems encountered during all stages of protein formulation development. In this publication, we present novel excipients, tryptophan-mPEGs (Trp-mPEGs) of 2 and 5 kDa molecular weight and suggest their use in protein formulation. The synthesis and physico-chemical characterization of the excipients are described. Possible cytotoxic and hemolytic activities of the Trp-mPEGs were examined. Turbidity, 90° static light scatter, intrinsic fluorescence, fluorescence after staining the samples with Nile Red and fluorescence microscopy were used to study the inhibitory effect of the Trp-mPEGs on the aggregation of salmon calcitonin (sCT) in different buffer systems and at various molar ratios. Aggregation of sCT was reduced significantly with increasing concentrations of Trp-mPEG 2 kDa. A 10-fold molar excess of Trp-mPEG 2 kDa suppressed almost completely the aggregation of sCT in 10mM sodium citrate buffer (pH 6) for up to 70 h. Trp-mPEG 5 kDa also reduced the aggregation of sCT, though less pronounced than Trp-mPEG 2 kDa. Low aggregation of sCT was measured after approximately 10 days in 10mM sodium citrate buffer, pH 5, with a 10-fold molar excess of Trp-mPEG 2 kDa. This paper shows that Trp-mPEGs are potent excipients in reducing the aggregation of sCT. Trp-mPEGs are superior to dansyl-PEGs concerning the stabilization of sCT in a harsh environment, wherein sCT is prone to aggregation. Trp-mPEGs might therefore also be used for stabilization of other biopharmaceuticals prone to aggregation.

  5. Structural determinants of salmon calcitonin bioactivity: the role of the Leu-based amphipathic alpha-helix.

    Science.gov (United States)

    Andreotti, Giuseppina; Méndez, Blanca López; Amodeo, Pietro; Morelli, Maria A Castiglione; Nakamuta, Hiromichi; Motta, Andrea

    2006-08-25

    Salmon calcitonin (sCT) forms an amphipathic helix in the region 9-19, with the C-terminal decapeptide interacting with the helix (Amodeo, P., Motta, A., Strazzullo, G., Castiglione Morelli, M. A. (1999) J. Biomol. NMR 13, 161-174). To uncover the structural requirements for the hormone bioactivity, we investigated several sCT analogs. They were designed so as to alter the length of the central helix by removal and/or replacement of flanking residues and by selectively mutating or deleting residues inside the helix. The helix content was assessed by circular dichroism and NMR spectroscopies; the receptor binding affinity in human breast cancer cell line T 47D and the in vivo hypocalcemic activity were also evaluated. In particular, by NMR spectroscopy and molecular dynamics calculations we studied Leu(23),Ala(24)-sCT in which Pro(23) and Arg(24) were replaced by helix inducing residues. Compared with sCT, it assumes a longer amphipathic alpha-helix, with decreased binding affinity and one-fifth of the hypocalcemic activity, therefore supporting the idea of a relationship between a definite helix length and bioactivity. From the analysis of other sCT mutants, we inferred that the correct helix length is located in the 9-19 region and requires long range interactions and the presence of specific regions of residues within the sequence for high binding affinity and hypocalcemic activity. Taken together, the structural and biological data identify well defined structural parameters of the helix for sCT bioactivity.

  6. The role of the area postrema in the anorectic effects of amylin and salmon calcitonin: behavioral and neuronal phenotyping.

    Science.gov (United States)

    Braegger, Fiona E; Asarian, Lori; Dahl, Kirsten; Lutz, Thomas A; Boyle, Christina N

    2014-10-01

    Amylin reduces meal size by activating noradrenergic neurons in the area postrema (AP). Neurons in the AP also mediate the eating-inhibitory effects of salmon calcitonin (sCT), a potent amylin agonist, but the phenotypes of the neurons mediating its effect are unknown. Here we investigated whether sCT activates similar neuronal populations to amylin, and if its anorectic properties also depend on AP function. Male rats underwent AP lesion (APX) or sham surgery. Meal patterns were analysed under ad libitum and post-deprivation conditions. The importance of the AP in mediating the anorectic action of sCT was examined in feeding experiments of dose-response effects of sCT in APX vs. sham rats. The effect of sCT to induce Fos expression was compared between surgery groups, and relative to amylin. The phenotype of Fos-expressing neurons in the brainstem was examined by testing for the co-expression of dopamine beta hydroxylase (DBH) or tryptophan hydroxylase (TPH). By measuring the apposition of vesicular glutamate transporter-2 (VGLUT2)-positive boutons, potential glutamatergic input to amylin- and sCT-activated AP neurons was compared. Similar to amylin, an intact AP was necessary for sCT to reduce eating. Further, co-expression between Fos activation and DBH after amylin or sCT did not differ markedly, while co-localization of Fos and TPH was minor. Approximately 95% of neurons expressing Fos and DBH after amylin or sCT treatment were closely apposed to VGLUT2-positive boutons. Our study suggests that the hindbrain pathways engaged by amylin and sCT share many similarities, including the mediation by AP neurons.

  7. Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats.

    Science.gov (United States)

    Feigh, Michael; Hjuler, Sara T; Andreassen, Kim V; Gydesen, Sofie; Ottosen, Ida; Henriksen, Jan Erik; Beck-Nielsen, Henning; Christiansen, Claus; Karsdal, Morten A; Henriksen, Kim

    2014-08-15

    We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present study we hypothesized that oral sCT as pharmacological intervention 1) exerted anti-hyperglycemic efficacy, and 2) enhanced insulin action in DIO-streptozotocin (DIO-STZ) diabetic rats. Diabetic hyperglycemia was induced in male selectively bred DIO rats by a single low dose (30mg/kg) injection of STZ. Oral sCT by gavage was delivered as once-daily administration with lead-in (2mg/kg) and maintenance (0.5mg/kg) dose of oral sCT for a total of 21 days. Food intake, body weight, blood glucose, HbA1c, glucose and insulin tolerance test, and parameters of insulin sensitivity were investigated. Plasma glucoregulatory hormones and pancreatic insulin content were analyzed. Oral sCT treatment induced a pronounced anorectic action during the 7 days lead-in period and markedly reduced food intake and body weight in conjunction with improved glucose homeostasis. During the maintenance period, oral sCT normalized food intake and attenuated weight loss, albeit sustained glycemic control by reducing fasting blood glucose and HbA1c levels compared to those of vehicle-treated rats at the end of study. Notably, plasma levels of insulin, glucagon, leptin and adiponectin were unaltered, albeit insulin action was enhanced in conjunction with protection of pancreatic insulin content. The results of the present study indicate that oral sCT exerts a novel insulin-sensitizing effect to improve glucose metabolism in obesity and type 2 diabetes.

  8. Calcium, magnesium, and phosphorus metabolism, and parathyroid-calcitonin function during prolonged exposure to elevated CO2 concentrations on submarines.

    Science.gov (United States)

    Messier, A A; Heyder, E; Braithwaite, W R; McCluggage, C; Peck, A; Schaefer, K E

    1979-01-01

    Studies of calcium and phosphorus metabolism and acid-base balance were carried out on three Fleet Ballistic Missile (FBM) submarines during prolonged exposure to elevated concentrations of CO2. The average CO2 concentration in the submarine atmosphere during patrols ranged from 0.85% to 1% CO2. In the three studies, in which 9--15 subjects participated, the urinary excretion of calcium and phosphate fell during the first three weeks to a level commensurate with a decrease in plasma calcium and increase in phosphorus. In the fourth week of one patrol, a marked increase was found in urinary calcium excretion, associated with a rise in blood PCO2 and bicarbonate. Urinary calcium excretion decreased again during the 5th to 8th week, with a secondary decrease in blood pH and plasma calcium. During the third patrol, the time course of acid-base changes corresponded well with that found during the second patrol. There was a trend toward an increase in plasma calcium between the fourth and fifth week commensurate with the transient rise in pH and bicarbonate. Plasma parathyroid and calcitonin hormone activities were measured in two patrols and no significant changes were found. Hydroxyproline excretion decreased in the three-week study and remained unchanged in the second patrol, which lasted 57 days. It is suggested that during prolonged exposure to low levels of CO2 (up to 1% CO2), calcium metabolism is controlled by the uptake and release of CO2 in the bones. The resulting phases in bone buffering, rather than renal regulation, determine acid-base balance.

  9. The association of single nucleotide polymorphisms in the calcitonin gene with primary osteoarthritis of the knee in Mexican mestizo population.

    Science.gov (United States)

    Magaña, J J; Muñoz, B; Borgonio-Cuadra, V M; Razo-Estrada, C; González-Huerta, C; Cortés-González, S; Albores, A; Miranda-Duarte, A

    2013-10-01

    Primary osteoarthritis (OA) is a multifactorial disorder with several genetics factors involved. Calcitonin (CT) has been suggested to possess chondroprotective effects and could play an important role in the pathogenesis of OA. The aim of this study was to investigate whether genetic variations in or adjacent to the CT gene may be associated with primary OA of the knee in Mexican mestizo population. We conducted a case-control study to investigate the association between six single nucleotide polymorphisms at the CT locus and OA of the knee in 107 cases and 106 controls. Cases were patients >40 years of age, with a body mass index (BMI) ≤ 27 and a radiologic score for OA of the knee ≥ 2. Controls were subjects >40 years of age with a radiologic score <2. Non-conditional logistic regression was developed to evaluate risk magnitude. The G allele and GT genotype frequencies of the G-706T polymorphism and the C allele and CC genotype of the C-778T polymorphism were significantly higher in patients with OA than in control subjects. The GG genotype of the G-706T was associated with lower risk of the development of OA of the knee. According to the results, the G-706T and the C-778T polymorphisms were related to the Cdx1 and Mzf1 transcription factor binding sites, respectively. Therefore, these could be related to regulation sequences in the CT gene promoter. In conclusion, G-706T and C-778T polymorphisms in the CT gene are significantly associated with the development of primary OA of the knee.

  10. Calcitonin gene-related peptide promotes cellular changes in trigeminal neurons and glia implicated in peripheral and central sensitization

    Directory of Open Access Journals (Sweden)

    Cady Ryan J

    2011-12-01

    Full Text Available Abstract Background Calcitonin gene-related peptide (CGRP, a neuropeptide released from trigeminal nerves, is implicated in the underlying pathology of temporomandibular joint disorder (TMD. Elevated levels of CGRP in the joint capsule correlate with inflammation and pain. CGRP mediates neurogenic inflammation in peripheral tissues by increasing blood flow, recruiting immune cells, and activating sensory neurons. The goal of this study was to investigate the capability of CGRP to promote peripheral and central sensitization in a model of TMD. Results Temporal changes in protein expression in trigeminal ganglia and spinal trigeminal nucleus were determined by immunohistochemistry following injection of CGRP in the temporomandibular joint (TMJ capsule of male Sprague-Dawley rats. CGRP stimulated expression of the active forms of the MAP kinases p38 and ERK, and PKA in trigeminal ganglia at 2 and 24 hours. CGRP also caused a sustained increase in the expression of c-Fos neurons in the spinal trigeminal nucleus. In contrast, levels of P2X3 in spinal neurons were only significantly elevated at 2 hours in response to CGRP. In addition, CGRP stimulated expression of GFAP in astrocytes and OX-42 in microglia at 2 and 24 hours post injection. Conclusions Our results demonstrate that an elevated level of CGRP in the joint, which is associated with TMD, stimulate neuronal and glial expression of proteins implicated in the development of peripheral and central sensitization. Based on our findings, we propose that inhibition of CGRP-mediated activation of trigeminal neurons and glial cells with selective non-peptide CGRP receptor antagonists would be beneficial in the treatment of TMD.

  11. Effect of calcitonin gene-related peptide on the neurogenesis of rat adipose-derived stem cells in vitro.

    Directory of Open Access Journals (Sweden)

    Qin Yang

    Full Text Available Calcitonin gene-related peptide (CGRP promotes neuron recruitment and neurogenic activity. However, no evidence suggests that CGRP affects the ability of stem cells to differentiate toward neurogenesis. In this study, we genetically modified rat adipose-derived stem cells (ADSCs with the CGRP gene (CGRP-ADSCs and subsequently cultured in complete neural-induced medium. The formation of neurospheres, cellular morphology, and proliferative capacity of ADSCs were observed. In addition, the expression of the anti-apoptotic protein Bcl-2 and special markers of neural cells, such as Nestin, MAP2, RIP and GFAP, were evaluated using Western blot and immunocytochemistry analysis. The CGRP-ADSCs displayed a greater proliferation than un-transduced (ADSCs and Vector-transduced (Vector-ADSCs ADSCs (p<0.05, and lower rates of apoptosis, associated with the incremental expression of Bcl-2, were also observed for CGRP-ADSCs. Moreover, upon neural induction, CGRP-ADSCs formed markedly more and larger neurospheres and showed round cell bodies with more branching extensions contacted with neighboring cells widely. Furthermore, the expression levels of Nestin, MAP2, and RIP in CGRP-ADSCs were markedly increased, resulting in higher levels than the other groups (p<0.05; however, GFAP was distinctly undetectable until day 7, when slight GFAP expression was detected among all groups. Wnt signals, primarily Wnt 3a, Wnt 5a and β-catenin, regulate the neural differentiation of ADSCs, and CGRP gene expression apparently depends on canonical Wnt signals to promote the neurogenesis of ADSCs. Consequently, ADSCs genetically modified with CGRP exhibit stronger potential for differentiation and neurogenesis in vitro, potentially reflecting the usefulness of ADSCs as seed cells in therapeutic strategies for spinal cord injury.

  12. Coated minispheres of salmon calcitonin target rat intestinal regions to achieve systemic bioavailability: Comparison between intestinal instillation and oral gavage.

    Science.gov (United States)

    Aguirre, Tanira A S; Aversa, Vincenzo; Rosa, Mónica; Guterres, Sílvia S; Pohlmann, Adriana R; Coulter, Ivan; Brayden, David J

    2016-09-28

    Achieving oral peptide delivery is an elusive challenge. Emulsion-based minispheres of salmon calcitonin (sCT) were synthesized using single multiple pill (SmPill®) technology incorporating the permeation enhancers (PEs): sodium taurodeoxycholate (NaTDC), sodium caprate (C10), or coco-glucoside (CG), or the pH acidifier, citric acid (CA). Minispheres were coated with an outer layer of Eudragit® L30 D-55 (designed for jejunal release) or Surelease®/Pectin (designed for colonic release). The process was mild and in vitro biological activity of sCT was retained upon release from minispheres stored up to 4months. In vitro release profiles suggested that sCT was released from minispheres by diffusion through coatings due to swelling of gelatin and the polymeric matrix upon contact with PBS at pH6.8. X-ray analysis confirmed that coated minispheres dissolved at the intended intestinal region of rats following oral gavage. Uncoated minispheres at a dose of ~2000I.U.sCT/kg were administered to rats by intra-jejunal (i.j.) or intra-colonic (i.c.) instillation and caused hypocalcaemia. Notable sCT absolute bioavailability (F) values were: 5.5% from minispheres containing NaTDC (i.j), 17.3% with CG (i.c.) and 18.2% with C10 (i.c.). Coated minispheres administered by oral gavage at threefold higher doses also induced hypocalcaemia. A highly competitive F value of 2.7% was obtained for orally-administered sCT-minispheres containing CG (45μmol/kg) and coated with Eudragit®. In conclusion, the SmPill® technology is a potential dosage form for several peptides when formulated with PEs and coated for regional delivery. PK data from instillations over-estimates oral bioavailability and poorly predicts rank ordering of formulations.

  13. Basal Cell Carcinoma of the Umbilicus: A Comprehensive Literature Review

    Science.gov (United States)

    Cohen, Philip R

    2016-01-01

    Basal cell carcinoma (BCC) typically occurs in sun-exposed sites. Only 16 individuals with umbilical BCC have been described in the literature, and the characteristics of patients with umbilical BCC are summarized. PubMed was used to search the following terms: abdomen, basal cell carcinoma, basal cell nevus syndrome, and umbilicus. Papers with these terms and references cited within these papers were reviewed. BCC of the umbilicus has been reported in five men and 11 women; one man had two tumors. Two patients had basal cell nevus syndrome (BCNS). Other risk factors for BCC were absent. The tumor most commonly demonstrated nodular histology (64%, 9/14); superficial and fibroepithelioma of Pinkus variants were noted in three and two patients, respectively. The tumor was pigmented in eight individuals. Treatment was conventional surgical excision (87%, 13/15) or Mohs micrographic surgery (13%, 2/15); either adjuvant laser ablation or radiotherapy was performed in two patients. The prognosis after treatment was excellent with no recurrence or metastasis (100%, 16/16). In conclusion, BCC of the umbilicus is rare. It usually presents as a tumor with a non-aggressive histologic subtype in an individual with no risk factors for this malignancy. There has been no recurrence or metastasis following excision of the cancer. PMID:27738570

  14. Basal Cell Carcinoma Developing from Trichoepithelioma: Review of Three Cases

    Science.gov (United States)

    Satyanarayana, M. Ananta; Aryasomayajula, Sirish; Krishna, B.A. Rama

    2016-01-01

    Trichoepitheliomas (TE) are benign tumours but occasionally can undergo transformation to malignant neoplasms more commonly as Basal Cell Carcinoma (BCC). The correct diagnosis between these tumours is very important because basal cell carcinoma is locally aggressive neoplasm and requires total surgical excision with wide healthy margins while trichoepithelioma needs simple excision. We describe three patients who developed basal cell carcinoma with facial trichoepitheliomas. The only clinical feature that distinguished the carcinomas from the trichoepitheliomas was their larger size, in all three patients, one patient with recurrent, hyper pigmented swelling with surface ulceration and in another patient there are multiple trichoepitheliomas, and other family members are also affected. The history, clinical features and histopathological findings were suggestive of the evolution of basal cell carcinoma directly from trichoepithelioma in our first two cases, but in the third case TE and BCC were separate lesions on face and we are uncertain about whether the BCC developed independently or by transformation from a trichoepithelioma. Based on our clinicopathological observations in the three patients and reports in the recent literature, BCC with follicular differentiation and trichoepithelioma are considered to be highly related. PMID:27134936

  15. PERIANTH DEVELOPMENT IN THE BASAL MONOCOT TRIGLOCHIN MARITIMA (JUNCAGINACEAE)

    DEFF Research Database (Denmark)

    Buzgo, Matyas; Soltis, Douglas E.; Soltis, Pamela S.;

    2006-01-01

    Basal monocots exhibit considerable variation in inflorescence and floral structure. In some cases, such as Triglochin maritima, it is not clear whether the lateral and terminal structures of the inflores- cence are flowers or pseudanthia, or where the limits between flowers and inflorescence lie...

  16. Metacomprehension during Basal Reader Instruction: Do Teachers Promote It?

    Science.gov (United States)

    Schmitt, Maribeth Cassidy; Baumann, James F.

    1990-01-01

    Analyzes elementary teachers' interactions with students during guided reading of basal reader selections to determine the extent to which the interactions promote students' metacomprehension abilities. Finds that teachers assumed most of the responsibility for students' comprehension themselves rather than conducting the lessons in a manner that…

  17. Utilizing Psycholinguistic Insights in Teaching via the Basal Reader.

    Science.gov (United States)

    Newman, Harold

    Ideas of educational psycholinguists Frank Smith and Kenneth Goodman can be combined with the ideas presented in current basal reader manuals to help teachers teach reading more effectively. Since reading and speaking are parallel processes, teachers may invite children to "read" with them, hearing the melody of language as they point to…

  18. Saccade learning with concurrent cortical and subcortical basal ganglia loops

    Directory of Open Access Journals (Sweden)

    Steve eN'guyen

    2014-04-01

    Full Text Available The Basal Ganglia is a central structure involved in multiple cortical and subcortical loops. Some of these loops are believed to be responsible for saccade target selection. We study here how the very specific structural relationships of these saccadic loops can affect the ability of learning spatial and feature-based tasks.We propose a model of saccade generation with reinforcement learning capabilities based onour previous basal ganglia and superior colliculus models. It is structured around the interactions of two parallel cortico-basal loops and one tecto-basal loop. The two cortical loops separately deal with spatial and non-spatial information to select targets in a concurrent way. The subcortical loop is used to make the final target selection leading to the production of thesaccade. These different loops may work in concert or disturb each other regarding reward maximization. Interactions between these loops and their learning capabilities are tested on different saccade tasks.The results show the ability of this model to correctly learn basic target selection based on different criteria (spatial or not. Moreover the model reproduces and explains training dependent express saccades toward targets based on a spatial criterion. Finally, the model predicts that in absence of prefrontal control, the spatial loop should dominate.

  19. Mephedrone alters basal ganglia and limbic neurotensin systems.

    Science.gov (United States)

    German, Christopher L; Hoonakker, Amanda H; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-01

    Mephedrone (4-methylmethcathinone) is a synthetic cathinone designer drug that alters pre-synaptic dopamine (DA) activity like many psychostimulants. However, little is known about the post-synaptic dopaminergic impacts of mephedrone. The neuropeptide neurotensin (NT) provides inhibitory feedback for basal ganglia and limbic DA pathways, and post-synaptic D1 -like and D2 -like receptor activity affects NT tissue levels. This study evaluated how mephedrone alters basal ganglia and limbic system NT content and the role of NT receptor activation in drug consumption behavior. Four 25 mg/kg injections of mephedrone increased NT content in basal ganglia (striatum, substantia nigra and globus pallidus) and the limbic regions (nucleus accumbens core), while a lower dosage (5 mg/kg/injection) only increased striatal NT content. Mephedrone-induced increases in basal ganglia NT levels were mediated by D1 -like receptors in the striatum and the substantia nigra by both D1 -like and D2 -like receptors in the globus pallidus. Mephedrone increased substance P content, another neuropeptide, in the globus pallidus, but not in the dorsal striatum or substantia nigra. Finally, the NT receptor agonist PD149163 blocked mephedrone self-administration, suggesting reduced NT release, as indicated by increased tissue levels, likely contributing to patterns of mephedrone consumption.

  20. Basal ganglia play a crucial role in decision making

    OpenAIRE

    Thibaut, Florence

    2016-01-01

    Many studies have suggested that the striatum, located at the interface of the cortico-basal ganglia-thalamic circuit, consists of separate circuits that serve distinct functions It plays an important role in motor planning, value processing, and decision making.

  1. Normal sexual dimorphism in the human basal ganglia.

    NARCIS (Netherlands)

    Rijpkema, M.J.P.; Everaerd, D.S.; Pol, C.; Franke, B.; Tendolkar, I.; Fernandez, G.S.E.

    2012-01-01

    Male and female brains differ in both structure and function. Investigating this sexual dimorphism in healthy subjects is an important first step to ultimately gain insight into sex-specific differences in behavior and risk for neuropsychiatric disorders. The basal ganglia are among the main regions

  2. [Successful therapy of metastatic basal cell carcinoma with vismodegib].

    Science.gov (United States)

    Zutt, M; Mazur, F; Bergmann, M; Lemke, A J; Kaune, K M

    2014-11-01

    A 71-year-old man presented with giant basal cell carcinoma on the abdomen which had metastasized. He was treated with oral vismodegib. Both the primary ulcerated tumor on the abdomen and the metastases responded. Vismodegib was well tolerated without significant side effects. The tumor recurred promptly after vismodegib was discontinued, and then was resistant to therapy when vismodegib was re-administered.

  3. Polymorphism in SFTPD gene affects assembly and constitutional serum levels of surfactant protein D in a Lebanese population

    DEFF Research Database (Denmark)

    Fakih, Dalia; Chamat, Soulaima; Medlej-Hashim, Myrna;

    2014-01-01

    the distribution profile of serum constitutional SP-D in the Lebanese population and to investigate the genetic influence of single nucleotide polymorphism (SNP) rs721917 within SP-D gene (SFTPD) on its multimerization and its serum basal level. The C/T alleles at this SNP level lead respectively either...... to a threonine or methionine at position 11 of the SP-D protein. SP-D was measured by ELISA in serum taken from 97 healthy subjects. The p.Met11Thr SNP was genotyped. Different forms of SP-D were separated by gel filtration chromatography. Basal serum SP-D levels varied extensively, over a range of 108.3 ng...

  4. CALCIUM REGULATING HORMONES IN SERUM AND BONE MASS DENSITY IN PATIENTS WITH DIABETES MELLITUS

    Institute of Scientific and Technical Information of China (English)

    颜晓东; 黄忠; 胡映玉

    2003-01-01

    Objective To investigate the changes of calcium regulating hormones in serum and bone mass in patients with diabetes mellitus.Methods The levels of estradiol (E2), testosterone (T), total triiodthyronine (TT3), total thyroid hormone(TT4), parathyroid hormone (PTH-SP), calci-tonin (CT) were measured in serum of 227 patients with diabetes and 268 healthy controls by radioim-munoassay, and bone mass density (BMD) at lumbar vertebrae, hip, foream were measured by dual energy X-ray absorptiometry (DEXA). The subjects were divided into three age groups.Results T of male in three age subgroups of diabetes was significantly lower (P<0.01 or P<0.05) and PTH was significantly higher (P< 0.001 or P< 0.01) than that in controls. BMD at lumbar 3, lumbar 4 in diabetes was lower than that in controls but BMD at hip, foream was higher.Conclusion The level of T declines and PTH increases in diabetes. Bone mass loss mostly occurs at lumbar vertebrae in diabetes patients.

  5. Basal jawed vertebrate phylogenomics using transcriptomic data from Solexa sequencing.

    Directory of Open Access Journals (Sweden)

    Ming Chen

    Full Text Available The traditionally accepted relationships among basal jawed vertebrates have been challenged by some molecular phylogenetic analyses based on mitochondrial sequences. Those studies split extant gnathostomes into two monophyletic groups: tetrapods and piscine branch, including Chondrichthyes, Actinopterygii and sarcopterygian fishes. Lungfish and bichir are found in a basal position on the piscine branch. Based on transcriptomes of an armored bichir (Polypterus delhezi and an African lungfish (Protopterus sp. we generated, expressed sequences and whole genome sequences available from public databases, we obtained 111 genes to reconstruct the phylogenetic tree of basal jawed vertebrates and estimated their times of divergence. Our phylogenomic study supports the traditional relationship. We found that gnathostomes are divided into Chondrichthyes and the Osteichthyes, both with 100% support values (posterior probabilities and bootstrap values. Chimaeras were found to have a basal position among cartilaginous fishes with a 100% support value. Osteichthyes were divided into Actinopterygii and Sarcopterygii with 100% support value. Lungfish and tetrapods form a monophyletic group with 100% posterior probability. Bichir and two teleost species form a monophyletic group with 100% support value. The previous tree, based on mitochondrial data, was significantly rejected by an approximately unbiased test (AU test, p = 0. The time of divergence between lungfish and tetrapods was estimated to be 391.8 Ma and the divergence of bichir from pufferfish and medaka was estimated to be 330.6 Ma. These estimates closely match the fossil record. In conclusion, our phylogenomic study successfully resolved the relationship of basal jawed vertebrates based on transtriptomes, EST and whole genome sequences.

  6. Calving fluxes and basal melt rates of Antarctic ice shelves.

    Science.gov (United States)

    Depoorter, M A; Bamber, J L; Griggs, J A; Lenaerts, J T M; Ligtenberg, S R M; van den Broeke, M R; Moholdt, G

    2013-10-03

    Iceberg calving has been assumed to be the dominant cause of mass loss for the Antarctic ice sheet, with previous estimates of the calving flux exceeding 2,000 gigatonnes per year. More recently, the importance of melting by the ocean has been demonstrated close to the grounding line and near the calving front. So far, however, no study has reliably quantified the calving flux and the basal mass balance (the balance between accretion and ablation at the ice-shelf base) for the whole of Antarctica. The distribution of fresh water in the Southern Ocean and its partitioning between the liquid and solid phases is therefore poorly constrained. Here we estimate the mass balance components for all ice shelves in Antarctica, using satellite measurements of calving flux and grounding-line flux, modelled ice-shelf snow accumulation rates and a regional scaling that accounts for unsurveyed areas. We obtain a total calving flux of 1,321 ± 144 gigatonnes per year and a total basal mass balance of -1,454 ± 174 gigatonnes per year. This means that about half of the ice-sheet surface mass gain is lost through oceanic erosion before reaching the ice front, and the calving flux is about 34 per cent less than previous estimates derived from iceberg tracking. In addition, the fraction of mass loss due to basal processes varies from about 10 to 90 per cent between ice shelves. We find a significant positive correlation between basal mass loss and surface elevation change for ice shelves experiencing surface lowering and enhanced discharge. We suggest that basal mass loss is a valuable metric for predicting future ice-shelf vulnerability to oceanic forcing.

  7. The non-active stellar chromosphere: Ca II basal flux

    Science.gov (United States)

    Pérez Martínez, M. I.; Schröder, K.-P.; Hauschildt, P.

    2014-11-01

    We analyse high-resolution, high-s/n European Southern Observatories (ESO)-archive spectra (from UVES, the UV echelle spectrograph) of 76 inactive or modestly active stars of spectral type G to M, main sequence and giants. Using PHOENIX model photospheres with Ca II K lines that match the observed line profiles, we (i) revise the effective temperatures, (ii) obtain a precise surface flux scale for each star and (iii) directly determine the exact surface fluxes of each Ca II K chromospheric emission with respect to the photospheric line profile. We find that our stellar sample exhibits a lower boundary to its chromospheric surface flux distribution with an unprecedented definition. From a subsample of the 25 least active stars, we obtain a simple empirical formula for the basal Ca II flux as a function of effective temperature: log {F^basal_{Ca II(H+K)}} = 7.05(± 0.31) log {T_eff} - 20.86(± 1.15). This is in good agreement with the Mg II basal flux. In a direct comparison with the large body of Mt Wilson S-measurements of the chromospheric Ca II emission and its well-defined cut-off, excellent agreement is achieved as well. A new result, however, is the small scatter of the least active star's fluxes about the basal flux. It is about 25 per cent and equals the residual uncertainties of our approach. At the same time, we do not find any evidence for a gravity dependence within these limits. This strongly confirms the basal flux as a well-defined and universal phenomenon, which characterizes every inactive chromosphere.

  8. Effect of dietary feed additives on haematological and serum biochemical parameters of broiler chickens.

    Directory of Open Access Journals (Sweden)

    Alonge EO

    2016-08-01

    Full Text Available The effect of dietary feed additives on haematological and serum biochemical parameters of broiler chickens was evaluated. 180 day-old Arbor acre broiler chicks were weighed and randomly allotted to five dietary treatments with 3 replicates of 12 birds each. Broiler starter diet (2855.7 kcal/kg ME; 23.01% and finisher diet (2911 kcal/kg; 20.71% CP were formulated. Dietary treatments were control diet (basal diet without additives, OXYT diet (basal diet with oxytetracycline at 600 ppm as antibiotic, GRO-UP diet (basal diet with probiotic at 500 ppm, MOS-500 diet (basal diet with mannan oligosaccharide at 500 ppm and MOS-1000 diet (basal diet with mannan oligosaccharide at 1000 ppm. Feed and water were supplied ad libitum. At the end of weeks 4 and 8, blood samples were collected and analyzed. The haematological and serum biochemical parameters of broiler chickens fed diets containing feed additives at the starter phase were not statistically significant (P> 0.05. At the finisher phase, there were no significant (P> 0.05 differences in all the parameters measured except in the heterophils and eosinophils where birds fed the control diets had the lowest value among all treatments. Serum globulin values were significantly (P< 0.05 different as birds fed diets containing OXYT (antibiotics recorded the lowest value among all treatments. The inclusion of prebiotics and probiotics in the diets of broiler chickens elicited no adverse effect on haematological and serum biochemical parameters, thus, they can be used as replacement for antibiotics.

  9. Research Progress of Calcitonin as Treatment for Osteoporosis%降钙素治疗骨质疏松症的研究进展

    Institute of Scientific and Technical Information of China (English)

    连建强

    2011-01-01

    Osteoporosis treatment is mainly drug therapy,which can be preliminariely categorized into three major series of inhibiting bone absorption, promoting bone formation, and promoting bone calcification.Calcitonin treatment of osteoporosis effect, usage and dosage, and the combined use of other drugs are reviewed here, with the focus of the promoting fracture healing, elminiating pain function of calcitonin besides the inhibition of bone loss.%骨质疏松症的治疗主要以药物治疗为主,该类药物初步可分为抑制骨吸收、促进骨形成、促进骨钙化三大系列.现就降钙素(抑制骨吸收药)对骨质疏松症的治疗作用、用法、用量以及与其他类药物联合应用进行综述,重点阐述降钙素不仅可抑制骨丢失,还可促进骨折愈合、消除骨痛.

  10. The Dual Amylin- and Calcitonin-Receptor Agonist KBP-042 Increases Insulin Sensitivity and Induces Weight Loss in Rats with Obesity

    DEFF Research Database (Denmark)

    Hjuler, Sara Toftegaard; Gydesen, Sofie; Andreassen, Kim Vietz

    2016-01-01

    Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s.c. ad...... combines two highly relevant features, namely weight loss and insulin sensitivity, and is thus an excellent candidate for chronic treatment of obesity and insulin resistance....... a sustained weight loss of up to 20% without any significant weight reduction in the pair-fed groups. Decreases in adipose tissues and lipid deposition in the liver were observed, while plasma adiponectin was increased and plasma leptin levels were decreased. Acute administration of KBP-042 led to impaired......Objective: In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 μg/kg-10 μg/kg) compared with saline-treated and pair-fed controls. Methods: Rats with obesity received daily s...

  11. Developmental localization of calcitonin gene-related peptide in dorsal sensory axons and ventral motor neurons of mouse cervical spinal cord.

    Science.gov (United States)

    Kim, Jeongtae; Sunagawa, Masanobu; Kobayashi, Shiori; Shin, Taekyun; Takayama, Chitoshi

    2016-04-01

    Calcitonin gene-related peptide (CGRP) is a 37-amino-acid neuropeptide, synthesized by alternative splicing of calcitonin gene mRNA. CGRP is characteristically distributed in the nervous system, and its function varies depending on where it is expressed. To reveal developmental formation of the CGRP network and its function in neuronal maturation, we examined the immunohistochemical localization of CGRP in the developing mouse cervical spinal cord and dorsal root ganglion. CGRP immunolabeling (IL) was first detected in motor neurons on E13, and in ascending axons of the posterior funiculus and DRG neurons on E14. CGRP-positive sensory axon fibers entered Laminae I and II on E16, and Laminae I through IV on E18. The intensity of the CGRP-IL gradually increased in both ventral and dorsal horns during embryonic development, but markedly decreased in the ventral horn after birth. These results suggest that CGRP is expressed several days after neuronal settling and entry of sensory fibers, and that the CGRP network is formed in chronological and sequential order. Furthermore, because CGRP is markedly expressed in motor neurons when axons are vastly extending and innervating targets, CGRP may also be involved in axonal elongation and synapse formation during normal development.

  12. Serum and tissue iodine concentrations in rats fed diets supplemented with kombu powder or potassium iodide.

    Science.gov (United States)

    Yoshida, Munehiro; Mukama, Ayumi; Hosomi, Ryota; Fukunaga, Kenji; Nishiyama, Toshimasa

    2014-01-01

    Serum and tissue iodine concentration was measured in rats fed a diet supplemented with powdered kombu (Saccharina sculpera) or potassium iodide to evaluate the absorption of iodine from kombu. Eighteen male 5-wk-old Wistar rats were divided into three groups and fed a basal AIN93G diet (iodine content, 0.2 mg/kg) or the basal diet supplemented with iodine (183 mg/kg) either in the form of kombu powder or potassium iodine (KI) for 4 wk. There were no differences in weight gain or serum biochemistry tests (alanine aminotransferase and aspartate aminotransferase activity, and total serum cholesterol and triglyceride concentration) after iodine supplementation. In addition, serum levels of the thyroid hormones thyroxine and triiodothyronine, as well as thyroid-stimulating hormone, were not affected. On the other hand, serum and tissue (thyroid, liver and kidney) iodine concentrations were markedly elevated after iodine supplementation. There was no difference in thyroid iodine concentration between KI and kombu supplementation. However, there was a significant difference observed in the iodine concentrations of serum, liver and kidney between the two iodine sources; rats fed KI had iodine concentrations in these tissues 1.8 to 1.9 times higher than those in rats fed kombu powder. These results suggest that the absorption of iodine from kombu is reduced compared to that from potassium iodide.

  13. Effects of the Basal Boundary on Debris-flow Dynamics

    Science.gov (United States)

    Iverson, R. M.; Logan, M.; Lahusen, R. G.; Berti, M.

    2006-12-01

    Data aggregated from 37 large-scale experiments reveal some counterintuitive effects of bed roughness on debris-flow dynamics. In each experiment 10 m3 of water-saturated sand and gravel, mixed with 1 to 12% silt and clay by dry weight, was abruptly released from a gate at the head of a 2-m wide, 1.2-m deep, 82.5-m long rectangular flume inclined 31° throughout most of its length and adjoined to a gently sloping, planar runout surface at its toe. The flume's basal boundary consisted of either a smooth, planar concrete surface or a concrete surface roughened with a grid of conical bumps. Tilt-table tests with dry debris-flow sediment showed that this roughness imparted a basal friction angle of 38°, comparable to the sediment's internal friction angle of 38-42°, whereas the smooth-bed friction angle was 28°. About 20 electronic sensors installed in the flume yielded data on flow speeds and depths as well as basal stresses and pore pressures. Behavior observed in all experiments included development of steep, unsaturated, coarse-grained debris-flow snouts and tapering, liquefied, fine-grained tails. Flows on the rough bed were typically about 50% thicker and 20% slower than flows on the smooth bed, although the rough bed caused snout steepening that enabled flow fronts to move faster than expected, given the increased bed friction. Moreover, flows on rough beds ran out further than flows on smooth beds owing to enhanced grain-size segregation and lateral levee formation. With the rough bed, measured basal stresses and pore pressures differed little from values expected from static gravitational loading of partially liquefied debris. With the smooth bed, however, measured basal stresses and pore pressures were nearly twice as large as expected values. This anomaly resulted from flow disturbance at the upstream lips of steel plates in which sensors were mounted. The lips produced barely visible ripples in otherwise smooth flow surfaces, yet sufficed to generate

  14. Low serum 25-hydroxyvitamin d concentrations are associated with increased risk for melanoma and unfavourable prognosis.

    Directory of Open Access Journals (Sweden)

    Benjamin Bade

    Full Text Available Low vitamin D status (serum 25(OHD concentration is associated with increased incidence and unfavourable outcome of various types of cancer. However, there are limited data on influence of serum 25(OHD on risk and prognosis of malignant melanoma.Basal serum 25(OHD concentrations were retrospectively analyzed in a cohort of melanoma patients (n = 324 and healthy controls (n = 141. We tested the hypothesis that serum 25(OHD concentrations are predictive of melanoma risk, thickness of primary melanomas, and overall survival (OS.Median serum 25(OHD concentrations were significantly lower (p = 0.004 in melanoma patients (median = 13.6 ng/ml as compared to controls (median = 15.6 ng/ml. Primary tumors of patients with low serum 25(OHD concentrations (20 ng/ml; median: 1.00 mm. Patients with 25(OHD serum concentrations in the lowest quartile had inferior overall survival (median: 80 months comparing with the highest quartile (median: 195 months; p = 0.049.Our data support the concept that serum 25(OHD concentrations are associated with risk and prognosis of melanoma. Whether normalizing serum 25(OHD concentrations in these patients improves outcomes will require testing in future clinical trials.

  15. Deformation Studies of NEEM, Greenland Basal Folded Ice

    Science.gov (United States)

    Keegan, K.; Dahl-Jensen, D.; Montagnat, M.; Weikusat, I.

    2015-12-01

    Deep Greenland ice cores and airborne radio echo sounding (RES) images have recently revealed that basal ice flow of the Greenland Ice Sheet is very unstable. In many locations, a basal layer of disturbed ice is observed. At the NEEM, Greenland site this folding occurs at the boundary between the Eemian and glacial ice regimes, indicating that differences in physical properties of the ice play a role in the disturbance. Past work in metallurgy and ice suggests that impurity content controls grain evolution and therefore deformation. We hypothesize that the differences in ice flow seen deep in the NEEM ice core are controlled by differences in the impurity content of the ice layers. Here we present results of fabric, grain size, impurity content, and deformation studies from samples above and below this unstable boundary in the ice sheet.

  16. MRI of germinomas arising from the basal ganglia and thalamus

    Energy Technology Data Exchange (ETDEWEB)

    Kim, D.I.; Yoon, P.H.; Ryu, Y.H.; Jeon, P.; Hwang, G.J. [Department of Diagnostic Radiology, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    1998-08-01

    We reviewed the MRI findings of germinomas originating from the basal ganglia, thalamus or deep white matter in 13 patients with 14 germinomas, excluding those in the suprasellar or pineal regions. Ten cases were confirmed as germinomas by stereotaxic biopsy, three by partial and one by total removal of the tumour. Analysis was focussed on the location and the signal characteristic of the tumour, haemorrhage, cysts within the tumour and any other associated findings. Thirteen of the tumours were in the basal ganglia and one in the thalamus. Haemorrhage was observed in seven patients, while twelve showed multiple cysts. Associated ipsilateral cerebral hemiatrophy was seen in three patients. The signal intensity of the parenchymal germinomas was heterogeneous on T1- and T2-weighted images due to haemorrhage, cysts and solid portions. We also report the MRI findings of germinomas in an early stage in two patients. (orig.) With 5 figs., 1 tab., 17 refs.

  17. Nevoid basal cell carcinoma syndrome (Gorlin-Goltz syndrome

    Directory of Open Access Journals (Sweden)

    N K Kiran

    2012-01-01

    Full Text Available The Gorlin-Goltz syndrome, also known as nevoid basal cell carcinoma syndrome (NBCCS, is an infrequent multisystemic disease inherited in a dominant autosomal way, which shows a high level of penetrance and variable expressiveness. It is characterized by odontogenic keratocysts in the jaw, multiple basal cell nevi carcinomas and skeletal abnormalities. This syndrome may be diagnosed early by a dentist by routine radiographic exams in the first decade of life, since the odontogenic keratocysts are usually one of the first manifestations of the syndrome. This case report presents a patient diagnosed as NBCCS by clinical, radiographic and histological findings in a 13-year-old boy. This paper highlights the importance of early diagnosis of NBCCS which can help in preventive multidisciplinary approach to provide a better prognosis for the patient.

  18. 基底节性失语%Basal Ganglia Aphasia

    Institute of Scientific and Technical Information of China (English)

    隆昱洲; 柳华; 艾青龙

    2008-01-01

    基底节病变常导致语言功能障碍,其表现彤式复杂,既可出现口语语言障碍,也可出现书面语语言障碍,几乎包括所有失语类型.文章就基底节解剖、基底节失语的定义、特点、机制以及病变部位对语言的影响做了综述.%Basal ganglion lesions often result in language impairment. Its patterns of manifestation are complicated. Patients may either have oral language disorders or written language disorders, which almost includes all types of aphasia, The article reviews the anatomy, definition, feature and mechanisms of basal ganglia aphasia as well as the effect of lesion sites on language.

  19. Idiopathic Basal Ganglia Calcification Presented with Impulse Control Disorder

    Science.gov (United States)

    Sahin, Cem; Levent, Mustafa; Akbaba, Gulhan; Kara, Bilge; Yeniceri, Emine Nese; Inanc, Betul Battaloglu

    2015-01-01

    Primary familial brain calcification (PFBC), also referred to as Idiopathic Basal Ganglia Calcification (IBGC) or “Fahr's disease,” is a clinical condition characterized by symmetric and bilateral calcification of globus pallidus and also basal ganglions, cerebellar nuclei, and other deep cortical structures. It could be accompanied by parathyroid disorder and other metabolic disturbances. The clinical features are dysfunction of the calcified anatomic localization. IBGC most commonly presents with mental damage, convulsion, parkinson-like clinical picture, and neuropsychiatric behavior disorders; however, presentation with impulse control disorder is not a frequent presentation. In the current report, a 43-year-old male patient who has been admitted to psychiatry policlinic with the complaints of aggressive behavior episodes and who has been diagnosed with impulse control disorder and IBGC was evaluated in the light of the literature. PMID:26246920

  20. Apical versus Basal Neurogenesis Directs Cortical Interneuron Subclass Fate

    Directory of Open Access Journals (Sweden)

    Timothy J. Petros

    2015-11-01

    Full Text Available Fate determination in the mammalian telencephalon, with its diversity of neuronal subtypes and relevance to neuropsychiatric disease, remains a critical area of study in neuroscience. Most studies investigating this topic focus on the diversity of neural progenitors within spatial and temporal domains along the lateral ventricles. Often overlooked is whether the location of neurogenesis within a fate-restricted domain is associated with, or instructive for, distinct neuronal fates. Here, we use in vivo fate mapping and the manipulation of neurogenic location to demonstrate that apical versus basal neurogenesis influences the fate determination of major subgroups of cortical interneurons derived from the subcortical telencephalon. Somatostatin-expressing interneurons arise mainly from apical divisions along the ventricular surface, whereas parvalbumin-expressing interneurons originate predominantly from basal divisions in the subventricular zone. As manipulations that shift neurogenic location alter interneuron subclass fate, these results add an additional dimension to the spatial-temporal determinants of neuronal fate determination.

  1. Basal autophagy is required for the efficient catabolism of sialyloligosaccharides.

    Science.gov (United States)

    Seino, Junichi; Wang, Li; Harada, Yoichiro; Huang, Chengcheng; Ishii, Kumiko; Mizushima, Noboru; Suzuki, Tadashi

    2013-09-13

    Macroautophagy is an essential, homeostatic process involving degradation of a cell's own components; it plays a role in catabolizing cellular components, such as protein or lipids, and damaged or excess organelles. Here, we show that in Atg5(-/-) cells, sialyloligosaccharides specifically accumulated in the cytosol. Accumulation of these glycans was observed under non-starved conditions, suggesting that non-induced, basal autophagy is essential for their catabolism. Interestingly, once accumulated in the cytosol, sialylglycans cannot be efficiently catabolized by resumption of the autophagic process, suggesting that functional autophagy is important for preventing sialyloligosaccharides from accumulating in the cytosol. Moreover, knockdown of sialin, a lysosomal transporter of sialic acids, resulted in a significant reduction of sialyloligosaccharides, implying that autophagy affects the substrate specificity of this transporter. This study thus provides a surprising link between basal autophagy and catabolism of N-linked glycans.

  2. Summary and Analysis of Adverse Drug Reactions Induced by Salmon Calcitonin for Injection%注射用鲑鱼降钙素不良反应汇总分析

    Institute of Scientific and Technical Information of China (English)

    苏娜; 吴斌; 徐?

    2013-01-01

    Objective To study the characteristics and the general pattern of adverse drug reactions ( ADR ) induced by salmon calcitonin. Methods The literatures of ADR induced by salmon calcitonin reported in the domestic medical journals during 1994-2012 were retrieved by means of CNKI,and a related database was established for statistical analysis. Results 15 cases of ADR induced by salmon calcitonin were retrieved,which including the integumentary system,cardiovascular system,digestive system,nervous system and allergic reaction. The advanced age group and women showed the higher incidence rate. Conclusion The adverse reactions caused by salmon calcitonin should arouse clinical attention to persist its rational use.%目的 探讨鲑鱼降钙素致不良反应的一般规律和特点.方法 检索(CNKI)1994年至2012年鲑鱼降钙素所致不良反应文献,并进行统计分析.结果 共检索到不良反应病例15例,包括皮肤系统、心血管系统、消化系统、神经系统和变态反应.在高年龄段和女性患者中发生率较高.结论 临床上应重视鲑鱼降钙素的不良反应,坚持合理用药.

  3. A Critical Review of Habit Learning and the Basal Ganglia

    OpenAIRE

    Seger, Carol A.; Spiering, Brian J.

    2011-01-01

    The current paper briefly outlines the historical development of the concept of habit learning and discusses its relationship to the basal ganglia. Habit learning has been studied in many different fields of neuroscience using different species, tasks, and methodologies, and as a result it has taken on a wide range of definitions from these various perspectives. We identify five common but not universal, definitional features of habit learning: that it is inflexible, slow or incremental, unco...

  4. Prospects for cannabinoid therapies in basal ganglia disorders

    OpenAIRE

    Fernández-Ruiz, Javier; Moreno-Martet, Miguel; Rodríguez-Cueto, Carmen; Palomo-Garo, Cristina; Gómez-Cañas, María; Valdeolivas, Sara; Guaza, Carmen; Romero, Julián; Guzmán, Manuel; Mechoulam, Raphael; Ramos, José A

    2011-01-01

    Cannabinoids are promising medicines to slow down disease progression in neurodegenerative disorders including Parkinson's disease (PD) and Huntington's disease (HD), two of the most important disorders affecting the basal ganglia. Two pharmacological profiles have been proposed for cannabinoids being effective in these disorders. On the one hand, cannabinoids like Δ9-tetrahydrocannabinol or cannabidiol protect nigral or striatal neurons in experimental models of both disorders, in which oxid...

  5. The proprioception and neuromuscular stability of the basal thumb joint

    OpenAIRE

    Mobargha, Nathalie

    2015-01-01

    OBJECTIVES The basal thumb joint, or the first carpometacarpal joint (CMC1) is an enigmatic construction. The concavo-convex shape of the CMC1 and wide range of movement, allows for both precision and power grips and is particularly susceptible to the development of osteoarthritis. Previous theories regarding the development of CMC1 osteoarthritis have focused on the role of gender, excessive joint load and ligament laxity as causative factors. An emerging theory is the role o...

  6. Translating structure to clinical properties of an ideal basal insulin.

    Science.gov (United States)

    Unnikrishnan, A G; Bantwal, Ganapathi; Sahay, R K

    2014-01-01

    There is a need for ideal basal insulin which can overcome the unmet need of a truly once daily insulin, with a flat peakless profile. Useful for all types of patients Insulin degludec is next generation insulin with a unique mode of protraction of forming soluble multi-hexamers and slow continuous absorption giving it a flat profile compared to the existing basal insulin. In patients with type 1 diabetes or with type 2 diabetes, at steady-state, the mean terminal half-life of insulin degludec was 25 hours, i.e., approximately twice as long as for insulin glargine (half-life of 12.1 hours). In once-daily dosing regimen it reaches steady state after approximately 3 days. The duration of action of insulin degludec was estimated to be beyond 42 hours in euglycaemic clamp studies and this gives the unique opportunity of flexible time dosing which is not an available option with the existing basal insulin. The glucose-lowering effect is evenly distributed across a 24-hour dosing interval with insulin degludec having 4 times lower variability than insulin glargine. This is an important attribute given the narrow therapeutic window of insulin and the goal of achieving night time and inter-prandial glycaemic control without increasing the risk for hypoglycaemia, a goal that is challenging given the variability of absorption and lower PK half-lives of current basal insulin products. The combination of the ultra-long, flat and stable profile with an improved hour-to-hour and day-to-day variability could present an improved risk-benefit trade-off with the lower risk of hypoglycaemia, allowing for targeting improved levels of glycaemic control.

  7. Pluronic F68 enhanced the conformational stability of salmon calcitonin in both aqueous solution and lyophilized solid form.

    Science.gov (United States)

    Lee, Ting-Huei; Lin, Shan-Yang

    2011-11-01

    The effects of different surfactants on the conformational stability and structural similarity of salmon calcitonin (sCT) in aqueous solution and lyophilized forms were investigated by using microscopic Fourier transform infrared (FTIR) spectroscopy with second-derivative spectral analysis. Six surfactants, HCO-60, sodium dodecyl sulfate (SDS), Tween 80, PEG 400, Pluronic 68, and F127 were selected. The sCT aqueous solution with or without different surfactants was, respectively, incubated at 40°C for up to 35 h. sCT films were casted on the CaF(2) plates and IR spectra were collected as a function of incubation time. Second derivative analysis showed that the native sCT having a major α-helical structure was gradually changed to the combination of α-helix, random coil, and β-sheet conformations in aqueous solution at 40°C. Similar conformational changes with delayed β-sheet formation were obtained for sCT after co-incubation with all the surfactants except Pluronic F68. When the native sCT was freeze-dried alone, a marked conformational alteration was found as illustrated by a poor spectral correlation coefficient (r) value of 0.823 as compared to that of the unlyophilized native sCT. This r value was significantly deviated from 1, strongly indicating the influence of lyophilization stress on the surfactant-free sCT. The r value for sCT after lyophilizing with HCO-60, Pluronic F127, PEG 400, or Pluronic F68 was >0.9, suggesting the possible stabilization of these surfactants in the lyophilization process. The sCT sample after lyophilizing with Pluronic F68 showed a highest r value (>0.968), indicating the most optimal stabilization effect of Pluronic F68 for sCT sample via lyophilization. Pluronic F68 was found to be the preferential surfactant for preventing the secondary structure changes in aqueous solution at 40°C as well as in lyophilized powder.

  8. Youth hypertension cerebral hemorrhage in basal ganglia surgery operation analysis

    Institute of Scientific and Technical Information of China (English)

    Qi-Hua Wang; Da-Shuang Lu; Jie Cui; Bo-Lin Qiao; Jing-Chun Wang

    2016-01-01

    Objective:Discuss surgical treatment of youth hypertension cerebral hemorrhage in basal ganglia.Methods:Retrospective analysis from January 2012 to April 2015 were adopted to bone flap craniotomy decompression for removal of hematoma and drainage drilling two kinds of surgical treatment of 46 cases of young patients with hypertension cerebral hemorrhage in basal ganglia.Results:Surgical operation, 28 patients postoperative review head CT, no further hemorrhage cases, residual hematoma volume 2-6 mL. Drilling drainage in the treatment of 18 patients, 1 case was bleeding again given surgical operation to remove the hematoma and the rest of the 17 cases without bleeding again, after 3 d, 17 cases of patients of postoperative hematoma drainage thoroughly. After 6 months, 46 cases of patients with postoperative review, GOS score light disability 9 cases, moderate disability 33 cases, 4 cases were severely disabled, curative effect is satisfied.Conclusions:Two kinds of operative methods each have advantages and disadvantages, young patients with hypertension cerebral hemorrhage in basal ganglia should according to patients' disease progression after speed, on admission patient's state of consciousness and head CT measured on admission hematoma volume, respectively.

  9. Movement Disorders Following Cerebrovascular Lesion in the Basal Ganglia Circuit.

    Science.gov (United States)

    Park, Jinse

    2016-05-01

    Movement disorders are primarily associated with the basal ganglia and the thalamus; therefore, movement disorders are more frequently manifest after stroke compared with neurological injuries associated with other structures of the brain. Overall clinical features, such as types of movement disorder, the time of onset and prognosis, are similar with movement disorders after stroke in other structures. Dystonia and chorea are commonly occurring post-stroke movement disorders in basal ganglia circuit, and these disorders rarely present with tremor. Rarer movement disorders, including tic, restless leg syndrome, and blepharospasm, can also develop following a stroke. Although the precise mechanisms underlying the pathogenesis of these conditions have not been fully characterized, disruptions in the crosstalk between the inhibitory and excitatory circuits resulting from vascular insult are proposed to be the underlying cause. The GABA (gamma-aminobutyric acid)ergic and dopaminergic systems play key roles in post-stroke movement disorders. This review summarizes movement disorders induced by basal ganglia and thalamic stroke according to the anatomical regions in which they manifest.

  10. Effects of aging on basal fat oxidation in obese humans

    DEFF Research Database (Denmark)

    Solomon, Thomas; Marchetti, Christine M; Krishnan, Raj K

    2008-01-01

    Basal fat oxidation decreases with age. In obesity, it is not known whether this age-related process occurs independently of changes in body composition and insulin sensitivity. Therefore, body composition, resting energy expenditure, basal substrate oxidation, and maximal oxygen consumption (VO(2......)max) were measured in 10 older (age, 60 +/- 4 years; mean +/- SEM) and 10 younger (age, 35 +/- 4 years) body mass index-matched, obese, normal glucose-tolerant individuals. Fasting blood samples were also collected. Older subjects had slightly elevated fat mass (32.2 +/- 7.1 vs 36.5 +/- 6.7 kg, P...... = .16); however, waist circumference was not different between groups (104.3 +/- 10.3 vs 102.1 +/- 12.6 cm, P = .65). Basal fat oxidation was 22% lower (1.42 +/- 0.14 vs 1.17 +/- 0.22 mg/kg fat-free mass per minute, P = .03) in older subjects. The VO(2)max was also decreased in older individuals (44...

  11. Photodynamic therapy for basal cell skin cancer ENT-organs

    Directory of Open Access Journals (Sweden)

    V. N. Volgin

    2014-01-01

    Full Text Available Results of photodynamic therapy in 96 patients with primary and recurrent basal cell skin cancer of ENT-organs are represented. For photodynamic therapy the Russian-made photosensitizer Photoditazine at dose of 0.6–1.4 mg/kg was used. Parameters were selected taking into account type and extent of tumor and were as follows: output power – 0.1–3.0 W, power density – 0.1–1.3 W/cm2, light dose – 100–400 J/cm2. The studies showed high efficacy of treatment for primary and recurrent basal cell skin cancer of nose, ear and external auditory canal – from 87.5 to 94.7% of complete regression. Examples of efficacy of the method are represented in the article. High efficacy and good cosmetic effects allowed to make a conclusion about perspectivity of photodynamic therapy for recurrent basal cell skin cancer of ENT-organs. 

  12. Bacterial diversity of oil palm Elaeis guineensis basal stems

    Science.gov (United States)

    Amran, Afzufira; Jangi, Mohd Sanusi; Aqma, Wan Syaidatul; Yusof, Nurul Yuziana Mohd; Bakar, Mohd Faizal Abu; Isa, Mohd Noor Mat

    2016-11-01

    Oil palm, Elaeis guineensis is one of the major industrial production crops in Malaysia. Basal stem rot, caused by the white fungus, Ganoderma boninense, is a disease that reduces oil palm yields in most production areas of the world. Understanding of bacterial community that is associated with Ganoderma infection will shed light on how this bacterial community contributes toward the severity of the infection. In this preliminary study, we assessed the bacterial community that inhabit the basal stems of E. guineensis based on 16S rRNA gene as a marker using next generation sequencing platform. This result showed that a total of 84,372 operational taxonomic-units (OTUs) were identified within six samples analyzed. A total 55,049 OTUs were assigned to known taxonomy whereas 29,323 were unassigned. Cyanobacteria, Bacteroidetes, Firmicutes and Proteobacteria were the most abundant phyla found in all six samples and the unique taxonomy assigned for each infected and healthy samples were also identified. The findings from this study will further enhance our knowledge in the interaction of bacterial communities against Ganoderma infection within the oil palm host plant and for a better management of the basal stems rot disease.

  13. Proactive selective response suppression is implemented via the basal ganglia.

    Science.gov (United States)

    Majid, D S Adnan; Cai, Weidong; Corey-Bloom, Jody; Aron, Adam R

    2013-08-14

    In the welter of everyday life, people can stop particular response tendencies without affecting others. A key requirement for such selective suppression is that subjects know in advance which responses need stopping. We hypothesized that proactively setting up and implementing selective suppression relies on the basal ganglia and, specifically, regions consistent with the inhibitory indirect pathway for which there is scant functional evidence in humans. Consistent with this hypothesis, we show, first, that the degree of proactive motor suppression when preparing to stop selectively (indexed by transcranial magnetic stimulation) corresponds to striatal, pallidal, and frontal activation (indexed by functional MRI). Second, we demonstrate that greater striatal activation at the time of selective stopping correlates with greater behavioral selectivity. Third, we show that people with striatal and pallidal volume reductions (those with premanifest Huntington's disease) have both absent proactive motor suppression and impaired behavioral selectivity when stopping. Thus, stopping goals are used to proactively set up specific basal ganglia channels that may then be triggered to implement selective suppression. By linking this suppression to the striatum and pallidum, these results provide compelling functional evidence in humans of the basal ganglia's inhibitory indirect pathway.

  14. Pigmented basal cell carcinoma of the eyelid in Hispanics

    Directory of Open Access Journals (Sweden)

    Lily Koo Lin

    2008-10-01

    Full Text Available Lily Koo Lin1, Han Lee2, Eli Chang11Department of Oculoplastics, Doheny Eye Institute, Los Angeles, CA, USA; 2Department of Dermatology, Keck School of Medicine of the University of Southern California, Los Angeles, CA, USABackground: Pigmented basal cell carcinoma (PBCC of the eyelid has not been well cited in the literature, and is often overlooked in the differential diagnosis of pigmented eyelid lesions. We aim to describe PBCC of the eyelid in Hispanic patients.Methods: Retrospective review of patients with eyelid skin cancer who presented to the Department of Dermatology at the Keck School of Medicine of the University of Southern California and the Doheny Eye Institute from January 2002 to November 2005.Results: Sixty-nine of the 79 patients with eyelid skin cancer had basal cell carcinoma. Eight of these patients were Hispanic. Four of the eight Hispanic patients had PBCC.Conclusions: Although eyelid PBCC is regarded as a rare condition, it may occur more commonly in the Hispanic population and should be remembered in the differential diagnosis of pigmented eyelid lesions.Keywords: pigmented basal cell carcinoma, eyelid, skin cancer, lesions

  15. Lixisenatide as add-on therapy to basal insulin

    Directory of Open Access Journals (Sweden)

    Brown DX

    2013-12-01

    Full Text Available Dominique Xavier Brown, Emma Louise Butler, Marc Evans Diabetes Department, University Hospital Llandough, Cardiff, UK Abstract: Many patients with type 2 diabetes mellitus do not achieve target glycosylated hemoglobin A1c levels despite optimally titrated basal insulin and satisfactory fasting plasma glucose levels. Current evidence suggests that HbA1c levels are dictated by both basal glucose and postprandial glucose levels. This has led to a consensus that postprandial glucose excursions contribute to poor glycemic control in these patients. Lixisenatide is a once-daily, prandial glucagon-like peptide 1 (GLP-1 receptor agonist with a four-fold affinity for the GLP-1 receptor compared with native GLP-1. Importantly, lixisenatide causes a significant delay in gastric emptying time, an important determinant of the once-daily dosing regimen. An exendin-4 mimetic with six lysine residues removed at the C-terminal, lixisenatide has pronounced postprandial glucose-lowering effects, making it a novel incretin agent for use in combination with optimally titrated basal insulin. Lixisenatide exerts profound effects on postprandial glucose through established mechanisms of glucose-dependent insulin secretion and glucagon suppression in combination with delayed gastric emptying. This review discusses the likely place that lixisenatide will occupy in clinical practice, given its profound effects on postprandial glucose and potential to reduce glycemic variability. Keywords: lixisenatide, add-on therapy, insulin, GLP-1 receptor agonist, postprandial glucose, pharmacodynamics

  16. A Case of Basal Cell Adenoma of the Upper Lip

    Directory of Open Access Journals (Sweden)

    Masanori Kudoh

    2014-01-01

    Full Text Available Basal cell adenoma is a rare type of benign salivary gland tumor found most commonly in the parotid gland. We present a rare case of basal cell adenoma arising in the minor salivary gland of the upper lip. The patient was a 59-year-old Japanese man who visited our department in December 2012 with a chief complaint of a mass in the upper lip, which had increased in size over several years. A mobile, elastic, and relatively soft mass without tenderness was palpable in the upper lip region. The mucosa of the upper lip covering the mass was normal. Tumor extirpation was performed under local anesthesia. Histologically, the tumor had a capsule and was composed of islands of relatively uniform, monotonous cells. Immunohistochemically, the inner tumor comprised tubuloductal structures that showed strong staining for CK7, while the outer tumor showed weak staining for CK7. The outer tumor cells also stained positively for CD10 and p63. The MIB-1 (Ki-67 labeling index was extremely low. Basal cell adenoma was diagnosed based on these results. The postoperative course was uneventful 12 months after surgery and there has been no recurrence.

  17. The human serum metabolome.

    Directory of Open Access Journals (Sweden)

    Nikolaos Psychogios

    Full Text Available Continuing improvements in analytical technology along with an increased interest in performing comprehensive, quantitative metabolic profiling, is leading to increased interest pressures within the metabolomics community to develop centralized metabolite reference resources for certain clinically important biofluids, such as cerebrospinal fluid, urine and blood. As part of an ongoing effort to systematically characterize the human metabolome through the Human Metabolome Project, we have undertaken the task of characterizing the human serum metabolome. In doing so, we have combined targeted and non-targeted NMR, GC-MS and LC-MS methods with computer-aided literature mining to identify and quantify a comprehensive, if not absolutely complete, set of metabolites commonly detected and quantified (with today's technology in the human serum metabolome. Our use of multiple metabolomics platforms and technologies allowed us to substantially enhance the level of metabolome coverage while critically assessing the relative strengths and weaknesses of these platforms or technologies. Tables containing the complete set of 4229 confirmed and highly probable human serum compounds, their concentrations, related literature references and links to their known disease associations are freely available at http://www.serummetabolome.ca.

  18. Prospective investigation of serum anti-Müllerian hormone concentration in ovulatory intrauterine insemination patients: a preliminary study

    DEFF Research Database (Denmark)

    Freiesleben, N la Cour; Rosendahl, Mikkel; Johannsen, Trine Holm;

    2010-01-01

    This preliminary prospective study investigated serum anti-Müllerian hormone (AMH) through correlations to other basal parameters (123 patients) and according to ovarian response to 75 IU recombinant follicle-stimulating hormone (rFSH)/day (62 patients) in ovulatory patients' first rFSH treatment...

  19. Field measurement of basal forces generated by erosive debris flows

    Science.gov (United States)

    McCoy, S.W.; Tucker, G.E.; Kean, J.W.; Coe, J.A.

    2013-01-01

    It has been proposed that debris flows cut bedrock valleys in steeplands worldwide, but field measurements needed to constrain mechanistic models of this process remain sparse due to the difficulty of instrumenting natural flows. Here we present and analyze measurements made using an automated sensor network, erosion bolts, and a 15.24 cm by 15.24 cm force plate installed in the bedrock channel floor of a steep catchment. These measurements allow us to quantify the distribution of basal forces from natural debris‒flow events that incised bedrock. Over the 4 year monitoring period, 11 debris‒flow events scoured the bedrock channel floor. No clear water flows were observed. Measurements of erosion bolts at the beginning and end of the study indicated that the bedrock channel floor was lowered by 36 to 64 mm. The basal force during these erosive debris‒flow events had a large‒magnitude (up to 21 kN, which was approximately 50 times larger than the concurrent time‒averaged mean force), high‒frequency (greater than 1 Hz) fluctuating component. We interpret these fluctuations as flow particles impacting the bed. The resulting variability in force magnitude increased linearly with the time‒averaged mean basal force. Probability density functions of basal normal forces were consistent with a generalized Pareto distribution, rather than the exponential distribution that is commonly found in experimental and simulated monodispersed granular flows and which has a lower probability of large forces. When the bed sediment thickness covering the force plate was greater than ~ 20 times the median bed sediment grain size, no significant fluctuations about the time‒averaged mean force were measured, indicating that a thin layer of sediment (~ 5 cm in the monitored cases) can effectively shield the subjacent bed from erosive impacts. Coarse‒grained granular surges and water‒rich, intersurge flow had very similar basal force distributions despite

  20. The efficacy of Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin in the treatment for the patients with osteoporosis%仙灵骨葆胶囊联合阿仑膦酸钠片、鲑降钙素对骨质疏松症患者的治疗作用

    Institute of Scientific and Technical Information of China (English)

    曾文丛; 何伟

    2015-01-01

    Objective: To discuss the efficacy of Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin in the treatment of the patients with osteoporosis. Methods: Seventy-nine outpatients and inpatients with osteoporosis in our hospital from May, 2013 to May, 2014 were selected and divided into a control group (n=39, received alendronate sodium tablets and salmon calcitonin treatment) and an observation group (n=40, received Xianlinggubao capsule on the basis of the control group) by digital randomized method. The clinical efficacy was compared between two groups. Results:The efficiency and treatment effectiveness of the observation group were significantly higher than those of the control group (P0.05). The BMD of the observation group was significantly higher 3 ~ 12 months after treatment than before, and that of the control group. The S-P, S-Ca and BGP levels of all patients were significantly higher while the serum ALP was significantly lower after treatment than before (P0.05). Conclusion: Xianlinggubao capsule combined with alendronate sodium tablets and salmon calcitonin shows an obvious therapeutic effect in the treatment of the patients with osteoporosis and can improve bone metabolism index.%目的:探讨仙灵骨葆胶囊联合阿仑膦酸钠片、鲑降钙素对骨质疏松症患者的治疗作用。方法:选取2013年5月-2014年5月期间我院门诊和住院部就诊的骨质疏松症患者79例,采用随机数字表法将患者分为对照组(n=39,阿仑膦酸钠片联合鲑降钙素药物治疗)和观察组(n=40,在对照组基础上采用仙灵骨葆胶囊治疗),比较两组临床疗效。结果:观察组显效率和治疗有效率均明显高于对照组(P <0.05)。治疗前,两组患者骨密度值(BMD)、血磷(S-P)、血钙(S-Ca)、血清碱性磷酸酶(ALP)和血骨钙素(BGP)水平比较差异无统计学意义(P >0.05)。治疗3~12个月后,观察组 BMD 值

  1. Effects of salmon calcitonin on gene and protein expression of OPG and RANKL in bone marrow cells from ovariectomized rats%鲑鱼降钙素对去卵巢大鼠骨髓细胞OPG、RANKL基因和蛋白表达的影响

    Institute of Scientific and Technical Information of China (English)

    王键; 魏劲松; 龚颜; 曾荣

    2013-01-01

    [目的]观察鲑鱼降钙素(sCT)对去卵巢大鼠骨密度(BMD)、血清Ⅰ型胶原交联羧基末端肽(ICTP)变化的影响,以及骨髓细胞骨保护素(OPG)和核因子κB受体活化因子配体(RANKL)的基因表达和两者在胫骨骨骺端蛋白含量的变化.[方法]取3个月龄雌性SD大鼠24只,随机平均分3组:假手术组(Sham)、鲑鱼降钙素处理组(sCT)、安慰剂组(OVX).采用双侧卵巢切除术复制骨质疏松大鼠模型.术后2周CT组予鲑鱼降钙素皮下注射12周,应用双能X线吸收仪法(DXA)测BMD,ELISA法测量血清ICTP浓度,qRT-PCR法定量骨髓细胞OPG和RANKL的mRNA表达量,免疫组织化学染色法测定胫骨干骺端OPG和RANKL蛋白表达量.[结果]与OVX组比较,sCT组的腰椎BMD上升显著(P<0.05),但股骨BMD改变不明显(P>0.05);血清ICTP含量显著降低(P<0.05);骨髓细胞RANKL的mRNA表达量变化不大(P>0.05),但OPG的mRNA表达量升高(P<0.05),OPG/RANKL的比率升高(P<0.05);胫骨干骺端也呈现出RANKL蛋白改变不明显(P>0.05),而OPG的蛋白分泌增加(P<0.05),从而OPG/RANKL的比率高于OVX组(P<0.05)的现象.[结论]降钙素可以预防腰椎BMD的丢失,降低血清ICTP水平,在体内可能主要通过上调OPG的mRNA表达和蛋白分泌,影响OPG/RANKL/RANK系统,影响破骨细胞功能,抑制骨吸收,进而达到预防绝经后骨质疏松的目的.%[Objective] To observe the effects of salmon calcitonin on bone mineral density (BMD) , serum procollagen type I collagen cross - linked telopeptide ( ICTP) , gene expression of receptor activator of NF - tcB ligand ( RANKL) and os-teopretegerin (OPG) in bone marrow cells, as well as protein expression of OPG and RANKL in tibial metaphysis from ovariec-tomized rats. [Methods] Twenty -four healthy female SD rats, 3 months old, were randomly divided into three groups ( 8 in each) : the sham -operated control group (Sham) , the ovariectomized group (OVX) and the salmon calcitonin treated group

  2. Effects of salmon calcitonin on postmenopausal osteoporosis%鲑鱼降钙素治疗绝经后骨质疏松症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    熊萍; 董刚强; 李世云; 林勇; 饶进; 杜春; 苟晓琴; 李龙英

    2012-01-01

    目的 观察鲑鱼降钙素和凯思立D治疗绝经后骨质疏松症的疗效.方法 将128例绝经后骨质疏松症患者随机分为对照组和治疗组各64例,对照组口服凯思立D,1片/d;治疗组则在此基础上加用鲑鱼降钙素肌肉注射,50IU/次,1次/周,两组疗程均为6个月.治疗结束后,比较两组患者的疗效及不良反应情况.结果 治疗组总有效率为92.2%,明显高于对照组53.1%,差异有统计学意义(P<0.05);治疗组的骨密度较治疗前明显提高(P<0.05),而对照组的骨密度则无明显变化,差异无统计学意义(P>0.5).结论 鲑鱼降钙素联合凯思立D治疗绝经后骨质疏松症疗效好,可明显改善症状,增加骨密度.%Objective To evaluate the effect of salmon calcitonin on postmenopausal osteoporosis patients. Methods 128 cases of postmenopausal osteoporosis were randomly divided into treatment group (n = 64) and the control group (n = 64). The cases in control group were given orally Kaisili D, 1 slice per day. On this basis,the treatment group were intramuscularly injected salmon calcitonin 50IU once a week for 6 months continuously. Results The total efficacy was 92. 2% in treatment group higher than that of control group. Bone mineral density (BMD) in treatment group increased significantly after treatments(P0. 05). Conclusion Salmon calcitonin combined with Kaisili D in treatment of postmenopausal osteoporosis has a good effect, can obviously improve symptoms and increase the bone density.

  3. Diet affects resting, but not basal metabolic rate of normothermic Siberian hamsters acclimated to winter.

    Science.gov (United States)

    Gutowski, Jakub P; Wojciechowski, Michał S; Jefimow, Małgorzata

    2011-12-01

    We examined the effect of different dietary supplements on seasonal changes in body mass (m(b)), metabolic rate (MR) and nonshivering thermogenesis (NST) capacity in normothermic Siberian hamsters housed under semi-natural conditions. Once a week standard hamster food was supplemented with either sunflower and flax seeds, rich in polyunsaturated fatty acids (FA), or mealworms, rich in saturated and monounsaturated FA. We found that neither of these dietary supplements affected the hamsters' normal winter decrease in m(b) and fat content nor their basal MR or NST capacity. NST capacity of summer-acclimated hamsters was lower than that of winter-acclimated ones. The composition of total body fat reflected the fat composition of the dietary supplements. Resting MR below the lower critical temperature of the hamsters, and their total serum cholesterol concentration were lower in hamsters fed a diet supplemented with mealworms than in hamsters fed a diet supplemented with seeds. These results indicate that in mealworm-fed hamsters energy expenditure in the cold is lower than in animals eating a seed-supplemented diet, and that the degree of FA unsaturation of diet affects energetics of heterotherms, not only during torpor, but also during normothermy.

  4. 肝硬化患者血清钙磷及钙调节激素的检测及意义%Significance of detecting serum calcium, serum phosphorus and calcium-regulating hormones in patients with hepatic cirrhosis

    Institute of Scientific and Technical Information of China (English)

    王瑜

    2016-01-01

    目的:探讨检测肝硬化患者血清钙磷及钙调节激素包括甲状旁腺激素(PTH)、降钙素(CT)及25-羟维生素D3[25-(OH)D3]的临床意义。方法釆集83例肝硬化患者及66例正常人的血清,血清钙测定用偶氮砷Ⅲ比色法,血清磷测定用磷钼酸盐法;甲状旁腺激素、降钙素及2-羟维生素D3的测定采用电化学发光法。结果 Child- pugh C级肝功能患者与对照组、A级及B级比较血清钙降低(<0.05),血磷的变化在4组患者之间差异无统计学意义。C级肝功能患者与对照组、A级及B级比较CT(<0.05)及25-(OH)D3(<0.01)降低,PTH升高(<0.01)。结论肝硬化患者存在血清钙及其调节激素的代谢紊乱,并随病情发展而加重。监测肝硬化血清钙及相关激素水平的变化可能有助于判断肝功能损害程度。%Objective To evaluate clinical significance of detecting serum calcium, serum phosphorus and calcium-regulating hormones, including parathyroid hormone (PTH), calcitonin (CT) and 25-hydroxyvitamin D3 [25-(OH)D3] in patients with hepatic cirrhosis. Methods We collected serum samples of 83 patients with hepatic cirrhosis and 66 normal people. Serum calcium was detected by Arsenazo Ⅲ colorimetric method and serum phosphorus by molybdophosphate photometric method; Electrochemiluminescence method was used to detect parathyroid hormone, calcitonin and 25-hydroxyvitamin D3. Results In Child-pugh class C patients, serum calcium levels was significantly lower than in control group and in class A and B patients ( <0.05). Serum phosphorus level was no significantly different in the four groups. Child-pugh class C patients had significantly lower 25-(OH) D3 (P< 0.01) and CT ( <0.05) level, but higher PTH ( <0.01) level compared with control group and with class A and B. Conclusions In patients with hepatic cirrhosis, there were disturbances of serum calcium and calcium-regulating hormone, which deteriorate with

  5. Expression of stromelysin 3 in basal cell carcinomas.

    Science.gov (United States)

    Cribier, B; Noacco, G; Peltre, B; Grosshans, E

    2001-01-01

    Stromelysin 3 is a member of the metalloproteinase family, which is expressed in various remodelling processes. The prognosis of breast cancers and squamous cell carcinomas is correlated to the level of expression of this protein. The purpose of the present work was to evaluate the expression of stromelysin 3 in the major types of basal cell carcinomas. We selected cases of primary tumours that were fully excised, without previous biopsy: 40 Pinkus tumors, 40 superficial, 40 nodular, 38 morpheiform basal cell carcinomas and 10 cases showing deep subcutaneous or muscular invasion. Immunohistochemistry was carried out using monoclonal anti-ST3 antibodies (MC Rio, IGBMC Strasbourg), and evaluated on a semi-quantitative scale from 0 to 3. Positively stained cells were restricted to the periphery of the epithelial cells, which, by contrast, never expressed stromelysin 3. The global rate of expression was 27% in Pinkus tumors, 65% in superficial, 72.5% in nodular, 87% in morpheiform and 100% in deeply invasive carcinomas. The rates of tumours showing the highest number of positively stained cells (class 2 or 3) were respectively 7.5%, 20%, 45%, 63% and 100%. This systematic study of stromelysin3 expression in basal cell carcinomas confirms that it is a marker of poor prognosis, because the rate of positive tumours was much higher in aggressive carcinomas. Moreover, the majority of tumours showing an intense expression (i.e. the highest number of positively stained cells in their stroma) were of the morpheiform and deeply invasive types, which are of poor prognosis. Altogether, the studies performed on cutaneous tumours are consistent with the theory of stromelysin 3 playing an active role in tumour progression.

  6. Basal salivary cortisol secretion and susceptibility to upper respiratory infection.

    Science.gov (United States)

    Janicki-Deverts, Denise; Cohen, Sheldon; Turner, Ronald B; Doyle, William J

    2016-03-01

    The immunosuppressive effects of glucocorticoids (GCs) are well-established. However, whether the net effect of GC-elicited alterations in immune function is sufficient to influence a clinically relevant outcome in healthy adults has yet to be shown. The aim of the present study was to investigate whether inter-individual differences in basal salivary cortisol production are associated with increased risk and severity of infection and subsequent illness following experimental exposure to a virus that causes the common cold. The present analyses combine archival data from three viral-challenge studies. Participants were 608 healthy adults, aged 18 to 55 years (49.2% female; 65.8% white), who each completed a three-day saliva collection protocol; was subsequently exposed to a virus that causes the common cold; and monitored for 5 days for objective signs of infection (presence of challenge virus in nasal secretions) and clinical illness (mucus weight, mucociliary clearance time). Basal cortisol production (operationalized as the calculated area-under-the-curve averaged across the 3 days) showed a graded association with infection risk, with those producing higher levels of cortisol being at greater risk. Cortisol also showed a continuous association with duration of viral shedding, an indicator of viral replication and continuing infection, such that higher cortisol concentrations predicted more days of shedding. Cortisol was not, however, related to severity of objective illness. These findings are the first to demonstrate in healthy adults an association between basal cortisol production and an objectively measured and clinically relevant infectious disease outcome.

  7. A phylogenomic approach to resolve the basal pterygote divergence.

    Science.gov (United States)

    Simon, Sabrina; Strauss, Sascha; von Haeseler, Arndt; Hadrys, Heike

    2009-12-01

    One of the most fascinating Bauplan transitions in the animal kingdom was the invention of insect wings, a change that also contributed to the success and enormous diversity of this animal group. However, the origin of insect flight and the relationships of basal winged insect orders are still controversial. Three hypotheses have been proposed to explain the phylogeny of winged insects: 1) the traditional Palaeoptera hypothesis (Ephemeroptera + Odonata, Neoptera), 2) the Metapterygota hypothesis (Ephemeroptera, Odonata + Neoptera), and 3) the Chiastomyaria hypothesis (Odonata, Ephemeroptera + Neoptera). Neither phylogenetic analyses of single genes nor even multiple marker systems (e.g., molecular markers + morphological characters) have yet been able to conclusively resolve basal pterygote divergences. A possible explanation for the lack of resolution is that the divergences took place in the mid-Devonian within a short period of time and attempts to solve this problem have been confounded by the major challenge of finding molecular markers to accurately track these short ancient internodes. Although phylogenomic data are available for Neoptera and some wingless (apterygote) orders, they are lacking for the crucial Odonata and Ephemeroptera orders. We adopt a multigene approach including data from two new expressed sequence tag projects-from the orders Ephemeroptera (Baetis sp.) and Odonata (Ischnura elegans)-to evaluate the potential of phylogenomic analyses in clarifying this unresolved issue. We analyzed two data sets that differed in represented taxa, genes, and overall sequence lengths: maxspe (15 taxa, 125 genes, and 31,643 amino acid positions) and maxgen (8 taxa, 150 genes, and 42,541 amino acid positions). Maximum likelihood and Bayesian inference analyses both place the Odonata at the base of the winged insects. Furthermore, statistical hypotheses testing rejected both the Palaeoptera and the Metapterygota hypotheses. The comprehensive molecular data set

  8. Correlation transfer from basal ganglia to thalamus in Parkinson's disease.

    Science.gov (United States)

    Reitsma, Pamela; Doiron, Brent; Rubin, Jonathan

    2011-01-01

    Spike trains from neurons in the basal ganglia of parkinsonian primates show increased pairwise correlations, oscillatory activity, and burst rate compared to those from neurons recorded during normal brain activity. However, it is not known how these changes affect the behavior of downstream thalamic neurons. To understand how patterns of basal ganglia population activity may affect thalamic spike statistics, we study pairs of model thalamocortical (TC) relay neurons receiving correlated inhibitory input from the internal segment of the globus pallidus (GPi), a primary output nucleus of the basal ganglia. We observe that the strength of correlations of TC neuron spike trains increases with the GPi correlation level, and bursty firing patterns such as those seen in the parkinsonian GPi allow for stronger transfer of correlations than do firing patterns found under normal conditions. We also show that the T-current in the TC neurons does not significantly affect correlation transfer, despite its pronounced effects on spiking. Oscillatory firing patterns in GPi are shown to affect the timescale at which correlations are best transferred through the system. To explain this last result, we analytically compute the spike count correlation coefficient for oscillatory cases in a reduced point process model. Our analysis indicates that the dependence of the timescale of correlation transfer is robust to different levels of input spike and rate correlations and arises due to differences in instantaneous spike correlations, even when the long timescale rhythmic modulations of neurons are identical. Overall, these results show that parkinsonian firing patterns in GPi do affect the transfer of correlations to the thalamus.

  9. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia;

    2015-01-01

    INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... defects than standard excisions with 4 or 6 mm margins. Closure of skin defects was achieved by side-to-side closure in 49% and by local flaps in 40%. There were no relapses during the observation time. The safety, cosmetic and functional outcome were excellent. CONCLUSIONS: We recommend that MMS...

  10. Delayed Diagnosis: Giant Basal Cell Carcinoma of Scalp

    Directory of Open Access Journals (Sweden)

    Didem Didar Balcı,

    2008-07-01

    Full Text Available Although basal cell carcinoma (BCC is the most common form of skin cancer, the scalp lesions of BCC have been rarely reported. Giant BCC is defined as a tumor larger than 5 cm in diameter and only 0.5-1 % of all BCCs achieve this size. We report a case of giant BCC on the scalp that was treated with topical coticosteroids and antifungal shampoo for five years. BCC should be considered in the differential diagnosis in erythematous plaque type lesions resistant to therapy with long duration localized on the scalp.

  11. The basal ganglia: an overview of circuits and function.

    Science.gov (United States)

    Utter, Amy A; Basso, Michele A

    2008-01-01

    The technique of electrical stimulation of brain tissue-known clinically as deep brain stimulation (DBS)-is at the fore of treatment of human neurological disease. Here we provide a general overview highlighting the anatomy and circuitry of the basal ganglia (BG). We introduce common disease states associated with BG dysfunction and current hypotheses of BG function. Throughout this introductory review we direct the reader to other reviews in this special issue of Neuroscience and Biobehavioral Reviews highlighting the interaction between basic science and clinical investigation to more fully understand the BG in both health and disease.

  12. Basal cell carcinomas in elderly patients treated by cryotherapy

    OpenAIRE

    Chiriac A.; Mihaila D.; Foia L; Solovan C

    2013-01-01

    Anca Chiriac,1 Doina Mihaila,2 Liliana Foia,3, Caius Solovan4 1Department of Dermatology, Nicolina Medical Center, 2Department of Pathology, St Maria Children's Hospital, 3Surgical Department, Grigore T Popa University of Medicine and Pharmacy, Iaşi, Romania; 4Victor Babe University of Medicine, Timişoara, Romania Abstract: Basal cell carcinoma is a malignant skin tumor with high incidence in our country, especially in rural areas, on sun-exposed skin (particularly on the face) in ...

  13. Basal Forebrain Cholinergic System and Orexin Neurons: Effects on Attention

    Science.gov (United States)

    Villano, Ines; Messina, Antonietta; Valenzano, Anna; Moscatelli, Fiorenzo; Esposito, Teresa; Monda, Vincenzo; Esposito, Maria; Precenzano, Francesco; Carotenuto, Marco; Viggiano, Andrea; Chieffi, Sergio; Cibelli, Giuseppe; Monda, Marcellino; Messina, Giovanni

    2017-01-01

    The basal forebrain (BF) cholinergic system has an important role in attentive functions. The cholinergic system can be activated by different inputs, and in particular, by orexin neurons, whose cell bodies are located within the postero-lateral hypothalamus. Recently the orexin-producing neurons have been proved to promote arousal and attention through their projections to the BF. The aim of this review article is to summarize the evidence showing that the orexin system contributes to attentional processing by an increase in cortical acetylcholine release and in cortical neurons activity. PMID:28197081

  14. Fish protein intake induces fast-muscle hypertrophy and reduces liver lipids and serum glucose levels in rats.

    Science.gov (United States)

    Kawabata, Fuminori; Mizushige, Takafumi; Uozumi, Keisuke; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kishida, Taro

    2015-01-01

    In our previous study, fish protein was proven to reduce serum lipids and body fat accumulation by skeletal muscle hypertrophy and enhancing basal energy expenditure in rats. In the present study, we examined the precise effects of fish protein intake on different skeletal muscle fiber types and metabolic gene expression of the muscle. Fish protein increased fast-twitch muscle weight, reduced liver triglycerides and serum glucose levels, compared with the casein diet after 6 or 8 weeks of feeding. Furthermore, fish protein upregulated the gene expressions of a fast-twitch muscle-type marker and a glucose transporter in the muscle. These results suggest that fish protein induces fast-muscle hypertrophy, and the enhancement of basal energy expenditure by muscle hypertrophy and the increase in muscle glucose uptake reduced liver lipids and serum glucose levels. The present results also imply that fish protein intake causes a slow-to-fast shift in muscle fiber type.

  15. Interpreting serum risperidone concentrations.

    Science.gov (United States)

    Boerth, Joel M; Caley, Charles F; Goethe, John W

    2005-02-01

    Risperidone is an atypical antipsychotic commonly used for treatment of schizophrenia and other psychotic disorders. Although therapeutic drug monitoring is not routine for any of the atypical antipsychotics, serum antipsychotic concentrations are measured routinely to assess treatment nonadherence. In humans, risperidone is metabolized by cytochrome P450 2D6 to 9-hydroxyrisperidone; together these constitute the active moiety. Dose-proportional increases in serum concentrations have not been reported for the parent drug, but have been reported for 9-hydroxyrisperidone and the active moiety (i.e., the combined concentrations of risperidone and 9-hydroxyrisperidone). We describe a 34-year-old Caucasian man of Sicilian descent with a history of schizophrenia, disorganized type. He was suspected to be noncompliant with his risperidone therapy. Initially, active moiety risperidone concentrations increased linearly with prescribed dosage increases. However, with continued increases, active moiety concentrations adjusted downward and remained 17-36% below anticipated levels. We propose a method for estimating target active moiety concentrations of risperidone based on dosage-a method that may be used to guide clinicians in assessing nonadherence to risperidone treatment.

  16. The calcitonin receptor gene is a candidate for regulation of susceptibility to herpes simplex type 1 neuronal infection leading to encephalitis in rat.

    Directory of Open Access Journals (Sweden)

    Nada Abdelmagid

    Full Text Available Herpes simplex encephalitis (HSE is a fatal infection of the central nervous system (CNS predominantly caused by Herpes simplex virus type 1. Factors regulating the susceptibility to HSE are still largely unknown. To identify host gene(s regulating HSE susceptibility we performed a genome-wide linkage scan in an intercross between the susceptible DA and the resistant PVG rat. We found one major quantitative trait locus (QTL, Hse1, on rat chromosome 4 (confidence interval 24.3-31 Mb; LOD score 29.5 governing disease susceptibility. Fine mapping of Hse1 using recombinants, haplotype mapping and sequencing, as well as expression analysis of all genes in the interval identified the calcitonin receptor gene (Calcr as the main candidate, which also is supported by functional studies. Thus, using unbiased genetic approach variability in Calcr was identified as potentially critical for infection and viral spread to the CNS and subsequent HSE development.

  17. Safety and efficacy of ALD403, an antibody to calcitonin gene-related peptide, for the prevention of frequent episodic migraine

    DEFF Research Database (Denmark)

    Dodick, David W; Goadsby, Peter J; Silberstein, Stephen D

    2014-01-01

    to treatment allocation during the study. The primary objective was to assess safety at 12 weeks after infusion. The primary efficacy endpoint was the change from baseline to weeks 5-8 in the frequency of migraine days, as recorded in patient electronic diaries. Patients were followed up until 24 weeks...... and one had one serious adverse event, and in the placebo group, one patient had one serious adverse event. There were no differences in vital signs or laboratory safety data between the two treatment groups. The mean change in migraine days between baseline and weeks 5-8 was -5·6 (SD 3·0) for the ALD403......BACKGROUND: Calcitonin gene-related peptide (CGRP) is crucial in the pathophysiology of migraine. We assessed the safety, tolerability, and efficacy of ALD403, a genetically engineered humanised anti-CGRP antibody, for migraine prevention. METHODS: In this randomised, double-blind, placebo...

  18. Calcitonin gene-related peptide in blood: is it increased in the external jugular vein during migraine and cluster headache? A review

    DEFF Research Database (Denmark)

    Tfelt-Hansen, Peer; Le, Han

    2009-01-01

    The involvement of calcitonin gene-related peptide (CGRP) in migraine pathophysiological mechanisms is shown by the facts that CGRP can induce migraine and that two CGRP antagonists, olcegepant and telcagepant, are effective in the treatment of migraine attacks. Increase of the neuropeptide CGRP...... during migraine and cluster headache attacks in the extracerebral circulation as measured in the external jugular vein (EJV) has been regarded as an established fact. Then in 2005, a study, using the migraine patients as their own controls, showed; however, no changes of CGRP in EJV. For migraine...... there is thus some uncertainty as to whether CGRP is increased in all migraine patients and more research is needed. In contrast, there are three 'positive' studies in cluster headache in which both sumatriptan, O(2) and spontaneous resolution normalized CGRP. The source of an increase of CGRP in EJV is most...

  19. Effect of Chinese Herbal Fumigation Combined with Tuina on Vertigo and Concentrations of Endothelin and Calcitonin Gene-related Peptide in Patients with Vertebral Artery Cervical Spondylosis

    Institute of Scientific and Technical Information of China (English)

    Zhao Cheng-fei; Liu Xiao-an; Ding Yun

    2014-01-01

    Objective:To observe the effect of Chinese herbal fumigation combined with three-step tuina manipulation on concentration of endothelin (ET) and calcitonin gene-related peptide (CGRP) and vertigo in patients with vertebral artery cervical spondylosis (VACS). Methods:A total of 120 eligible cases were randomly allocated into an observation group and a control group, 60 in each group. Cases in the observation group were treated with Chinese herbal fumigation combined with three-step tuina manipulation, whereas cases in the control group were treated with oral Flunarizine Hydrochloride Capsules. Results: After treatment, vertigo in both groups was alleviated; there were intra-group significant differences in ET decrease and CGRP increase (P Conclusion: Chinese herbal fumigation combined with three-step tuina manipulation can regulate the levels of ET and CGRP and improve vertigo in patients with VACS. Its therapeutic efficacy is superior to oral Flunarizine Hydrochloride Capsules.

  20. Expression of calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in differing physiological states and following misoprostol administration.

    Science.gov (United States)

    Goharkhay, Nina; Lu, Jing; Felix, Juan C; Wing, Deborah A

    2007-09-01

    Our objective was to assess relative expression levels of mRNA for calcitonin gene-related peptide-receptor component protein (CGRP-RCP) in human myometrium in various physiological states. Using semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR), we analyzed myometrial samples from 46 women (10 menopausal, 10 nongravid premenopausal, 19 gravidae, and 7 premenopausal misoprostol-treated nongravid women) for the specific expression of CGRP-RCP mRNA. The expression of CGRP-RCP was significantly increased in gravid compared with nongravid myometrium ( P RCP expression were found among the other study groups. We concluded that the increased mRNA expression CGRP-RCP in gravid myometrium supports the possibility of involvement of CGRP in the control of myometrial contractility. Additional studies are necessary to evaluate the exact mechanism of action of CGRP and CGRP-RCP in human myometrium.

  1. Do sensory calcitonin gene-related peptide nerve fibres in the rat pelvic plexus supply autonomic neurons projecting to the uterus and cervix?

    Science.gov (United States)

    Houdeau, E; Barranger, E; Rossano, B

    2002-10-25

    Sensory nerve fibres containing calcitonin gene-related peptide (CGRP) innervate neurons of the paracervical ganglion (PCG) in the female rat pelvic plexus. We have combined retrograde tracing with immunocytochemistry to investigate whether CGRP-immunoreactive (-IR) fibres supply neurons targeting the genital tract. Of the total neurons projecting to either the uterine horns or the cervix, 38 and 41% received CGRP-IR innervation, respectively. All these neurons displayed choline acetyltransferase-IR, thus are cholinergic. They were found throughout the PCG and other pelvic plexus ganglia, namely accessory ganglia (AG) and hypogastric plexus (HP). Pelvic nerve section showed that afferent fibres in these nerves provided most of the CGRP-IR fibres supplying uterine- or cervical-related neurons in the PCG/AG, none in HP. It is suggested that such sensory-motor network may provide a local pathway for reflex control of genital tract activity, acting through cholinergic nerve projections.

  2. Calcitonin gene-related peptide (CGRP) and its receptor components in human and rat spinal trigeminal nucleus and spinal cord at C1-level

    DEFF Research Database (Denmark)

    Eftekhari, Sajedeh; Edvinsson, Lars

    2011-01-01

    was expressed in fibers of laminae I and II. The CGRP staining was similar in rat, except for CGRP positive neurons that were found close to the central canal. In C1, the receptor components were detected in laminae I and II, however these fibers were distinct from fibers expressing CGRP as verified by confocal...... to regions in the brainstem with Aδ- and C-fibers; this constitutes an essential part of the pain pathways activated in migraine attacks. Therefore it is of importance to identify the regions within the brainstem that processes nociceptive information from the trigeminovascular system, such as the spinal...... trigeminal nucleus (STN) and the C1-level of the spinal cord. Immunohistochemistry was used to study the distribution and relation between CGRP and its receptor components - calcitonin receptor-like receptor (CLR) and receptor activity modifying protein 1 (RAMP1) - in human and rat STN and at the C1-level...

  3. Role of Calcitonin Original Level Testing in Identifying Strains of Bloodstream Infections of Patients in ICU%降钙素原水平检测对鉴别重症监护病房血流感染患者菌种的作用

    Institute of Scientific and Technical Information of China (English)

    龚剑锋; 向镜芬; 杨祥; 孟启勇; 雷伟健

    2015-01-01

    目的:探讨PCT水平对鉴别重症监护病房血流感染患者菌种的价值。方法:选择2011年3月-2014年1月本院ICU患者131例作为研究对象,按照其菌种将其分为G-组、G+组及真菌组,比较各组PCT水平差异,并根据其ROC曲线判断血清PCT的诊断性能。结果:三组血清PCT中位数水平差异具有统计学意义(P<0.05);血清PCT水平对G-菌与G+菌及真菌所致的血流感染鉴别诊断性能较高。结论:血清PCT水平对于鉴别G-菌与G+菌或真菌引起的血流感染有一定的临床鉴别价值,但是对于G+菌与真菌引起的感染鉴别意义尚不明确。%Objective:To investigate the value of calcitonin original level in identifying bacterial bloodstream infections of patients in intensive care unit. Method:131 patients in ICU of our hospital from March 2011 to January 2014 were selected as the objects.They were divided into group G-,group G+and group fungi according to different strains.Differences in PCT levels were compared among the three groups and diagnostic performance of serum PCT was determined according to its ROC curve. Result:Differences in median serum PCT levels of the three groups were statistically significant.Serum PCT level has a higher diagnostic capacity in differentiating bloodstream infections caused by G-bacteria and G+bacteria or fungi.Conclusion:Serum PCT level plays a certain role in differentiating bloodstream infections caused by G-bacteria and G+bacteria or fungi,but it plays an uncertain role in differentiating infections caused by G+bacteria and fungi.

  4. Calcitonin blood test

    Science.gov (United States)

    ... skin is broken) References Bringhurst FR, Demay MB, Kronenberg HM. Hormones and disorders of mineral metabolism. In: Melmed S, Polonsky KS, Larsen PR, Kronenberg HM, eds. Williams Textbook of Endocrinology . 13th ed. ...

  5. Precore/basal core promoter mutants and hepatitis B viral DNA levels as predictors for liver deaths and hepatocellular carcinoma

    Institute of Scientific and Technical Information of China (English)

    Myron J Tong; Lawrence M Blatt; Jia-Horng Kao; Jason Tzuying Cheng; William G Corey

    2006-01-01

    AIM: To conduct a retrospective study in 400 chronic hepatitis B patients in order to identify hepatitis B viral factors associated with complications of liver disease or development of hepatocellular carcinoma.METHODS: The mean follow-up time was 83.6 ± 39.6mo. Alpha-fetoprotein test and abdominal ultrasound were used for cancer surveillance. Hepatitis B basal core promoter mutants, precore mutants, genotypes,hepatitis B viral DNA (HBV DNA) level and hepatitis B e antigen (HBeAg) were measured. Univariate analysis and logistic regression were used to assess odds ratios for viral factors related to liver deaths and hepatocellular carcinoma development.RESULTS: During follow-up, 38 patients had liver deaths not related to hepatocellular carcinoma. On multivariate analysis, older age [odds ratio: 95.74 (12.13-891.31);P < 0.0001], male sex [odds ratio: 7.61 (2.20-47.95);P = 0.006], and higher log10 HBV DNA [odds ratio:4.69 (1.16-20.43); P < 0.0001] were independently predictive for these liver related deaths. Also, 31 patients developed hepatocellular carcinoma. Multivariate analysis showed that older age [odds ratio: 26.51 (2.36-381.47);P = 0.007], presence of precore mutants [odds ratio:4.23 (1.53-19.58); P = 0.02] and presence of basal core promoter mutants [odds ratio: 2.93 (1.24-7.57); P =0.02] were independent predictors for progression to hepatocellular carcinoma.CONCLUSION: Our results show that high levels of baseline serum HBV DNA are associated with nonhepatocellular carcinoma-related deaths of liver failure,while genetic mutations in the basal core promoter and precore regions are predictive for development of hepatocellular carcinoma.

  6. Decreased serum hepcidin concentration correlates with brain iron deposition in patients with HBV-related cirrhosis.

    Directory of Open Access Journals (Sweden)

    Dong Lin

    Full Text Available PURPOSE: Excessive brain iron accumulation contributes to cognitive impairments in hepatitis B virus (HBV-related cirrhotic patients. The underlying mechanism remains unclear. Hepcidin, a liver-produced, 25-aminoacid peptide, is the major regulator of systemic iron metabolism. Abnormal hepcidin level is a key factor in some body iron accumulation or deficiency disorders, especially in those associated with liver diseases. Our study was aimed to explore the relationship between brain iron content in patients with HBV-related cirrhosis and serum hepcidin level. METHODS: Seventy HBV-related cirrhotic patients and forty age- sex-matched healthy controls were enrolled. Brain iron content was quantified by susceptibility weighted phase imaging technique. Serum hepcidin as well as serum iron, serum transferrin, ferritin, soluble transferrin receptor, total iron binding capacity, and transferrin saturation were tested in thirty cirrhotic patients and nineteen healthy controls. Pearson correlation analysis was performed to investigate correlation between brain iron concentrations and serum hepcidin, or other iron parameters. RESULTS: Cirrhotic patients had increased brain iron accumulation compared to controls in the left red nuclear, the bilateral substantia nigra, the bilateral thalamus, the right caudate, and the right putamen. Cirrhotic patients had significantly decreased serum hepcidin concentration, as well as lower serum transferring level, lower total iron binding capacity and higher transferrin saturation, compared to controls. Serum hepcidin level negatively correlated with the iron content in the right caudate, while serum ferritin level positively correlated with the iron content in the bilateral putamen in cirrhotic patients. CONCLUSIONS: Decreased serum hepcidin level correlated with excessive iron accumulation in the basal ganglia in HBV-related cirrhotic patients. Our results indicated that systemic iron overload underlined regional

  7. Clinical observation of Qianggu capsules combined with salmon calcitonin injection in the treatment of osteoporotic compression fractures in the elderly%强骨胶囊联合鲑鱼降钙素针剂辅助治疗老年骨质疏松性压缩骨折临床观察

    Institute of Scientific and Technical Information of China (English)

    杨国志; 李振武; 尹锐峰; 李志安

    2014-01-01

    Objective To investigate the clinical efficacy and the influence of Qianggu capsules combined with salmon calcitonin injection in the treatment of osteoporotic compression fractures in the elderly.Methods Two hundred and fifty-seven patients with osteoporotic thoracolumbar vertebral fractures were randomly divided into 3 groups.Patients in the observation group took oral medication of Qianggu capsules, combined with an intramuscular injection of salmon calcitonin injection.Patients in control group I took oral medication of Qianggu capsules only, and patients in control group II were intramuscularly injected with salmon calcitonin injection only.The clinical efficacy was observed.Bone mineral density (BMD) and the serum levels of osteocalcin (BGP), calcium, phosphorus, and alkaline phosphatase were detected before and after the treatment.Urinary contents of calcium, hydroxyproline, and creatinine were also detected.The calcium/creatinine ratio and hydroxyproline/creatinine ratio in urine were calculated.Results The total effective rate in the observation group was significantly higher than that in the control group I and the control group II ( P 0.05).After the treatment, no significant changes of serum phosphorus and urinary calcium/creatinine in 3 groups were observed, and no significant difference among 3 groups was observed (P>0.05).Conclusion The efficacy of Qianggu capsules combined with salmon calcitonin in the treatment of osteoporotic fractures in the elderly is assured.It can relieve pain, promote fracture healing, reduce the recurrence of fractures, and has no obvious adverse reaction.%目的:探讨强骨胶囊联合鲑鱼降钙素针剂辅助治疗老年骨质疏松性压缩骨折临床疗效及影响。方法257例胸腰椎骨质疏松性骨折患者随机分为3组,观察组口服强骨胶囊同时肌肉注射鲑鱼降钙素注射液,对照I组口服强骨胶囊,对照Ⅱ组肌肉注射鲑鱼降钙素针剂。观察临床疗效,测定治

  8. Basal Complex and Basal Venation of Odonata Wings: Structural Diversity and Potential Role in the Wing Deformation

    Science.gov (United States)

    Rajabi, H.; Ghoroubi, N.; Malaki, M.; Darvizeh, A.; Gorb, S. N.

    2016-01-01

    Dragonflies and damselflies, belonging to the order Odonata, are known to be excellent fliers with versatile flight capabilities. The ability to fly over a wide range of speeds, high manoeuvrability and great agility are a few characteristics of their flight. The architecture of the wings and their structural elements have been found to play a major role in this regard. However, the precise influence of individual wing components on the flight performance of these insects remains unknown. The design of the wing basis (so called basal complex) and the venation of this part are responsible for particular deformability and specific shape of the wing blade. However, the wing bases are rather different in representatives of different odonate groups. This presumably reflects the dimensions of the wings on one hand, and different flight characteristics on the other hand. In this article, we develop the first three-dimensional (3D) finite element (FE) models of the proximal part of the wings of typical representatives of five dragonflies and damselflies families. Using a combination of the basic material properties of insect cuticle, a linear elastic material model and a nonlinear geometric analysis, we simulate the mechanical behaviour of the wing bases. The results reveal that although both the basal venation and the basal complex influence the structural stiffness of the wings, it is only the latter which significantly affects their deformation patterns. The use of numerical simulations enabled us to address the role of various wing components such as the arculus, discoidal cell and triangle on the camber formation in flight. Our study further provides a detailed representation of the stress concentration in the models. The numerical analysis presented in this study is not only of importance for understanding structure-function relationship of insect wings, but also might help to improve the design of the wings for biomimetic micro-air vehicles (MAVs). PMID:27513753

  9. Clinical variants, stages, and management of basal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Lyubomir A Dourmishev

    2013-01-01

    Full Text Available Basal cell carcinoma (BCC is the most common paraneoplastic disease among human neoplasms. The tumor affects mainly photoexposed areas, most often in the head and seldom appears on genitalia and perigenital region. BCC progresses slowly and metastases are found in less than 0.5% of the cases; however, a considerable local destruction and mutilation could be observed when treatment is neglected or inadequate. Different variants as nodular, cystic, micronodular, superficial, pigment BCC are described in literature and the differential diagnosis in some cases could be difficult. The staging of BCC is made according to Tumor, Node, Metastasis (TNM classification and is essential for performing the adequate treatment. Numerous therapeutic methods established for treatment of BCC, having their advantages or disadvantages, do not absolutely dissolve the risk of relapses. The early diagnostics based on the good knowledge and timely organized and adequate treatment is a precondition for better prognosis. Despite the slow progress and numerous therapeutic methods, the basal cell carcinoma should not be underestimated.

  10. Basal autophagy protects cardiomyocytes from doxorubicin-induced toxicity.

    Science.gov (United States)

    Pizarro, Marcela; Troncoso, Rodrigo; Martínez, Gonzalo J; Chiong, Mario; Castro, Pablo F; Lavandero, Sergio

    2016-08-31

    Doxorubicin (Doxo) is one of the most effective anti-neoplastic agents but its cardiotoxicity has been an important clinical limitation. The major mechanism of Doxo-induced cardiotoxicity is associated to its oxidative capacity. However, other processes are also involved with significant consequences for the cardiomyocyte. In recent years, a number of studies have investigated the role of autophagy on Doxo-induced cardiotoxicity but to date it is not clear how Doxo alters that process and its consequence on cardiomyocytes viability. Here we investigated the effect of Doxo 1uM for 24h of stimulation on cultured neonatal rat cardiomyocytes. We showed that Doxo inhibits basal autophagy. This inhibition is due to both Akt/mTOR signaling pathway activation and Beclin 1 level decrease. To assess the role of autophagy on Doxo-induced cardiomyocyte death, we evaluated the effects 3-methyladenine (3-MA), bafilomycin A1 (BafA), siRNA Beclin 1 (siBeclin 1) and rapamycin (Rapa) on cell viability. Inhibition of autophagy with 3-MA, BafA and siBeclin 1 increased lactate dehydrogenase (LDH) release but, when autophagy was induced by Rapa, Doxo-induced cardiomyocyte death was decreased. These results suggest that Doxo inhibits basal autophagy and contributes to cardiomyocyte death. Activation of autophagy could be used as a strategy to protect the heart against Doxo toxicity.

  11. The evolution of floral biology in basal angiosperms.

    Science.gov (United States)

    Endress, Peter K

    2010-02-12

    In basal angiosperms (including ANITA grade, magnoliids, Choranthaceae, Ceratophyllaceae) almost all bisexual flowers are dichogamous (with male and female functions more or less separated in time), and nearly 100 per cent of those are protogynous (with female function before male function). Movements of floral parts and differential early abscission of stamens in the male phase are variously associated with protogyny. Evolution of synchronous dichogamy based on the day/night rhythm and anthesis lasting 2 days is common. In a few clades in Magnoliales and Laurales heterodichogamy has also evolved. Beetles, flies and thrips are the major pollinators, with various degrees of specialization up to large beetles and special flies in some large-flowered Nymphaeaceae, Magnoliaceae, Annonaceae and Aristolochiaceae. Unusual structural specializations are involved in floral biological adaptations (calyptras, inner staminodes, synandria and food bodies, and secretory structures on tepals, stamens and staminodes). Numerous specializations that are common in monocots and eudicots are absent in basal angiosperms. Several families are poorly known in their floral biology.

  12. Morphological elucidation of basal ganglia circuits contributing reward prediction

    Directory of Open Access Journals (Sweden)

    Fumino eFujiyama

    2015-02-01

    Full Text Available Electrophysiological studies in monkeys have shown that dopaminergic neurons respond to the reward prediction error. In addition, striatal neurons alter their responsiveness to cortical or thalamic inputs in response to the dopamine signal, via the mechanism of dopamine-regulated synaptic plasticity. These findings have led to the hypothesis that the striatum exhibits synaptic plasticity under the influence of the reward prediction error and conduct reinforcement learning throughout the basal ganglia circuits.The reinforcement learning model is useful; however, the mechanism by which such a process emerges in the basal ganglia needs to be anatomically explained. The actor–critic model has been previously proposed and extended by the existence of role sharing within the striatum, focusing on the striosome/matrix compartments. However, this hypothesis has been difficult to confirm morphologically, partly because of the complex structure of the striosome/matrix compartments. Here, we review recent morphological studies that elucidate the input/output organization of the striatal compartments.

  13. Coordinated Beating of Algal Flagella is Mediated by Basal Coupling

    Science.gov (United States)

    Wan, Kirsty; Goldstein, Raymond

    Cilia or flagella often exhibit synchronized behavior. This includes phase-locking, as seen in Chlamydomonas, and metachronal wave formation in the respiratory cilia of higher organisms. Since the observations by Gray and Rothschild of phase synchrony of nearby swimming spermatozoa, it has been a working hypothesis that synchrony arises from hydrodynamic interactions between beating filaments. Recent work on the dynamics of physically separated pairs of flagella isolated from the multicellular alga Volvox has shown that hydrodynamic coupling alone is sufficient for synchrony. However, the situation is more complex when considering multiple flagella on a single cell. We suggest that a mechanism, internal to the cell, provides an additional flagellar coupling. For instance, flagella of Chlamydomonas mutants deficient in filamentary connections between basal bodies are found to display markedly different synchronization from the wildtype. Diverse flagellar coordination strategies found in quadri-, octo- and hexadecaflagellates reveal further evidence that intracellular couplings between flagellar basal bodies compete with hydrodynamic interactions to determine the precise form of flagellar synchronization in unicellular algae.

  14. Carcinogenesis of basal cell carcinomas: genetics and molecular mechanisms.

    Science.gov (United States)

    Lacour, J P

    2002-04-01

    Basal cell carcinoma (BCC) of the skin is the most common type of cancer in humans. Like squamous cell carcinomas, they are also believed to be ultraviolet (UV)-induced, but several data suggest that some differences might exist in the mechanisms of their UV induction. The originating cells may arise from interfollicular basal cells, hair follicles or sebaceous glands, thus from a deeper zone than the SCC ones, which probably means exposure to different doses or wavelengths of UV. The p53 gene and the patched gene (PTCH) are major targets of UV for BCC induction. Mutations in p53 are present in about 56% of human BCC, even small early lesions. The "UV signature" is observed in 65% of them. Mutations in the PTCH play also a major role in BCC development, being responsible for hereditary BCCs in Gorlin's syndrome, sporadic BCC, and BCCs isolated from xeroderma pigmentosum, although with a lower incidence of "UV signature". Smoothened-activating mutations and PTCH2 mutations are also involved in BCC formation. Transgenic mice overexpressing Smoothened or Sonic hedgehog in the skin spontaneously produce skin lesions resembling human BCCs, but contrary to findings in the hairless albino mouse and with SCC, no data on experimental UV induction of BCCs are available.

  15. Treatment of nevoid basal cell carcinoma syndrome: a case report

    Science.gov (United States)

    2016-01-01

    Nevoid basal cell carcinoma syndrome (NBCCS), also known as Gorlin syndrome, is characterized by various embryological deformities and carcinoma formation. It is caused by PTCHI gene mutations and is autosomal dominantly inherited. Some of the main symptoms of NBCCS are multiple basal cell carcinomas, multiple keratocystic odontogenic tumors (KCOTs) of the mandible, hyperkeratosis of the palmar and plantar, skeletal deformity, calcification of the falx cerebri, and facial defomity. Recurrent KCOT is the main symptom of NBCCS and is present in approximately 90% of patients. In NBCCS, KCOTs typically occur in multiples. KCOTs can be detected in patients under the age of 10, and new and recurring cysts develop until approximately the age of 30. The postoperation recurrence rate is approximately 60%. This case report presents a 14-year-old female patient with a chief complaint of a cyst found in the maxilla and mandible. The patient was diagnosed with NBCCS, and following treatment of marsupialization and enucleation, the clinical results were satisfactory. PMID:27847737

  16. Mephedrone alters basal ganglia and limbic dynorphin systems.

    Science.gov (United States)

    German, Christopher L; Alburges, Mario E; Hoonakker, Amanda J; Fleckenstein, Annette E; Hanson, Glen R

    2014-08-25

    Mephedrone (4-methymethcathinone) is a synthetic cathinone designer drug that disrupts central nervous system (CNS) dopamine (DA) signaling. Numerous central neuropeptide systems reciprocally interact with dopaminergic neurons to provide regulatory counterbalance, and are altered by aberrant DA activity associated with stimulant exposure. Endogenous opioid neuropeptides are highly concentrated within dopaminergic CNS regions and facilitate many rewarding and aversive properties associated with drug use. Dynorphin, an opioid neuropeptide and kappa receptor agonist, causes dysphoria and aversion to drug consumption through signaling within the basal ganglia and limbic systems, which is affected by stimulants. This study evaluated how mephedrone alters basal ganglia and limbic system dynorphin content, and the role of DA signaling in these changes. Repeated mephedrone administrations (4 × 25 mg/kg/injection, 2-h intervals) selectively increased dynorphin content throughout the dorsal striatum and globus pallidus, decreased dynorphin content within the frontal cortex, and did not alter dynorphin content within most limbic system structures. Pretreatment with D1 -like (SCH-23380) or D2 -like (eticlopride) antagonists blocked mephedrone-induced changes in dynorphin content in most regions examined, indicating altered dynorphin activity is a consequence of excessive DA signaling. Synapse, 2014. © 2014 Wiley Periodicals, Inc.

  17. Familial idiopathic basal ganglia calcification (Fahr’s disease)

    Science.gov (United States)

    Mufaddel, Amir A.; Al-Hassani, Ghanem A.

    2014-01-01

    Familial idiopathic basal ganglia calcification (Fahr’s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr’s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr’s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr’s disease. PMID:24983277

  18. Familial idiopathic basal ganglia calcification (Fahr`s disease).

    Science.gov (United States)

    Mufaddel, Amir A; Al-Hassani, Ghanem A

    2014-07-01

    Familial idiopathic basal ganglia calcification (Fahr`s disease) is a rare neurodegenerative disorder characterized by symmetrical and bilateral calcification of the basal ganglia. Calcifications may also occur in other brain regions such as dentate nucleus, thalamus, and cerebral cortex. Both familial and non-familial cases of Fahr`s disease have been reported, predominantly with autosomal-dominant fashion. The disease has a wide range of clinical presentations, predominantly with neuropsychiatric features and movement disorders. Psychiatric features reported in the literature include: cognitive impairment, depression, hallucinations, delusions, manic symptoms, anxiety, schizophrenia-like psychosis, and personality change. Other clinical features include: Parkinsonism, ataxia, headache, seizures, vertigo, stroke-like events, orthostatic hypotension, tremor, dysarthria, and paresis. Fahr`s disease should be considered in the differential diagnosis of psychiatric symptoms, particularly when associated with movement disorder. The disease should be differentiated from other conditions that can cause intracranial calcification. No specific treatment is currently available. Further research is needed to bridge the gap existing in our current knowledge of the prevalence, etiology, symptoms, and treatment of Fahr`s disease.

  19. 不同产家鲑鱼降钙素治疗绝经后骨质疏松症的疗效与经济比较%Thecurativeeffectandtheeconomiccomparisonofdifferentproducers of salmon calcitonin in the treatment of patients with postmenopausal osteoporosis

    Institute of Scientific and Technical Information of China (English)

    赖习科

    2013-01-01

    Objective To compare the curative effect and economy of domestic and imported salmon calcitonin injection in the treatment of patients with postmenopausal osteoporosis. Methods 60 cases of postmenopausal osteoporosis were randomly divided into two groups,the control group were given imported salmon calcitonin injection treatment,while the observation group were given domestic salmon calcitonin injection treatment. Results There was no significant difference in the clinical effect and the bone density of patients with postmenopausal osteoporosis between the two groups(P>0.05).The price of domestic salmon calcitonin injection was lower than that of the import of salmon calcitonin injection. Conclusion Domestic salmon calcitonin injection combined with caltrate with vitamin D300 chewing tablets in the treatment of postmenopausal osteoporosis patients curative effect is reliable,and economical and practical.%目的比较国产与进口鲑鱼降钙素注射液治疗绝经后骨质疏松症的疗效与经济。方法60例绝经后骨质疏松症患者,分成观察组与对照组。对照组采用进口鲑鱼降钙素注射液治疗;观察组采用国产鲑鱼降钙素注射液治疗。结果两组疗效及绝经后骨质疏松症患者骨密度比较,差异均无统计学意义(P>0.05)。国产鲑鱼降钙素注射液价格低于进口鲑鱼降钙素注射液。结论国产鲑鱼降钙素注射液联合钙尔奇D300咀嚼片治疗绝经后骨质疏松症患者疗效可靠,而且经济实惠。

  20. Triple-negative breast cancer with brain metastases: a comparison between basal-like and non-basal-like biological subtypes

    NARCIS (Netherlands)

    A. Niwińska (Anna); W. Olszewski (Wojciech); M. Murawska (Magdalena); K. Pogoda (Katarzyna)

    2011-01-01

    textabstractThe aim of this study was to divide the group of triple-negative breast cancer patients with brain metastases into basal-like and non-basal-like biological subtypes in order to compare clinical features and survival rates in those two groups. A comprehensive analysis of 111 consecutive t

  1. Marine ice sheet model performance depends on basal sliding physics and sub-shelf melting

    Science.gov (United States)

    Gladstone, Rupert Michael; Warner, Roland Charles; Galton-Fenzi, Benjamin Keith; Gagliardini, Olivier; Zwinger, Thomas; Greve, Ralf

    2017-01-01

    Computer models are necessary for understanding and predicting marine ice sheet behaviour. However, there is uncertainty over implementation of physical processes at the ice base, both for grounded and floating glacial ice. Here we implement several sliding relations in a marine ice sheet flow-line model accounting for all stress components and demonstrate that model resolution requirements are strongly dependent on both the choice of basal sliding relation and the spatial distribution of ice shelf basal melting.Sliding relations that reduce the magnitude of the step change in basal drag from grounded ice to floating ice (where basal drag is set to zero) show reduced dependence on resolution compared to a commonly used relation, in which basal drag is purely a power law function of basal ice velocity. Sliding relations in which basal drag goes smoothly to zero as the grounding line is approached from inland (due to a physically motivated incorporation of effective pressure at the bed) provide further reduction in resolution dependence.A similar issue is found with the imposition of basal melt under the floating part of the ice shelf: melt parameterisations that reduce the abruptness of change in basal melting from grounded ice (where basal melt is set to zero) to floating ice provide improved convergence with resolution compared to parameterisations in which high melt occurs adjacent to the grounding line.Thus physical processes, such as sub-glacial outflow (which could cause high melt near the grounding line), impact on capability to simulate marine ice sheets. If there exists an abrupt change across the grounding line in either basal drag or basal melting, then high resolution will be required to solve the problem. However, the plausible combination of a physical dependency of basal drag on effective pressure, and the possibility of low ice shelf basal melt rates next to the grounding line, may mean that some marine ice sheet systems can be reliably simulated at

  2. Combined effect of Lactobacillus acidophilus and β-cyclodextrin on serum cholesterol in pigs.

    Science.gov (United States)

    Alonso, L; Fontecha, J; Cuesta, P

    2016-01-14

    A total of twenty-four Yorkshire gilt pigs of 6-7 weeks of age were used in a 2×2 factorial experiment to determine the individual and combined effects of the inclusion of two dietary factors (cholesterol rich, 3% β-cyclodextrin (BCD) and Lactobacillus acidophilus cultures) on total cholesterol and LDL-cholesterol levels in blood serum. Pigs were assigned randomly to treatment groups (n 6). Total serum cholesterol concentrations decreased after 3 weeks in all the experimental treatment groups, including diets with BCD, L. acidophilus or both. Similar trends were observed for serum LDL-cholesterol concentrations among the experimental treatments. No statistically significant differences from the control group were observed in either total serum cholesterol or LDL-cholesterol concentrations (Pacidophilus. However, significant differences in total serum cholesterol concentrations were observed when comparing the combined treatment group (BCD and L. acidophilus) with the control group, which consisted of a basal diet and sterile milk. The combined treatment group exhibited 17·9% lower total serum cholesterol concentration after 3 weeks. Similar significant differences were observed when comparing the combined effect experimental group with the control group after 3 weeks. The combined treatment group exhibited 27·9% lower serum LDL-cholesterol concentrations.

  3. Basal Cell Carcinoma in Type 2 Segmental Darier's Disease

    Directory of Open Access Journals (Sweden)

    Lynne Robertson

    2012-01-01

    Full Text Available Background. Darier's disease (DD, also known as Keratosis Follicularis or Darier-White disease, is a rare disorder of keratinization. DD can present as a generalized autosomal dominant condition as well as a localized or segmental postzygotic condition (Vázquez et al., 2002. Clinical features of DD include greasy, warty papules and plaques on seborrheic areas, dystrophic nails, palmo-plantar pits, and papules on the dorsum of the hands and feet. Objective. We report a case of basal cell carcinoma developing in a patient with type 2 segmental DD. Conclusion. According to the current literature, Type 2 segmental disease is a rare presentation of Darier's disease with only 8 previous cases reported to date. In addition, nonmelanoma skin cancer (NMSC arising from DD is rarely reported; however, there may be an association between DD and risk of carcinogenesis.

  4. Genomic analysis of smoothened inhibitor resistance in basal cell carcinoma.

    Science.gov (United States)

    Sharpe, Hayley J; Pau, Gregoire; Dijkgraaf, Gerrit J; Basset-Seguin, Nicole; Modrusan, Zora; Januario, Thomas; Tsui, Vickie; Durham, Alison B; Dlugosz, Andrzej A; Haverty, Peter M; Bourgon, Richard; Tang, Jean Y; Sarin, Kavita Y; Dirix, Luc; Fisher, David C; Rudin, Charles M; Sofen, Howard; Migden, Michael R; Yauch, Robert L; de Sauvage, Frederic J

    2015-03-09

    Smoothened (SMO) inhibitors are under clinical investigation for the treatment of several cancers. Vismodegib is approved for the treatment of locally advanced and metastatic basal cell carcinoma (BCC). Most BCC patients experience significant clinical benefit on vismodegib, but some develop resistance. Genomic analysis of tumor biopsies revealed that vismodegib resistance is associated with Hedgehog (Hh) pathway reactivation, predominantly through mutation of the drug target SMO and to a lesser extent through concurrent copy number changes in SUFU and GLI2. SMO mutations either directly impaired drug binding or activated SMO to varying levels. Furthermore, we found evidence for intra-tumor heterogeneity, suggesting that a combination of therapies targeting components at multiple levels of the Hh pathway is required to overcome resistance.

  5. Basal Secretion of Lysozyme from Human Airways in Vitro

    Directory of Open Access Journals (Sweden)

    Patricia Roger

    1999-01-01

    Full Text Available The aim of this study was to examine the basal release of lysozyme from isolated human lung tissues. Measurements of lysozyme in the fluids derived from lung preparations were performed using a rate-of-lysis assay subsequent to acidification of the biological samples. Lysozyme released from bronchial preparations into fluids was greater than that observed for parenchymal tissues. The lysozyme quantities detected in bronchial fluids were not modified by removal of the surface epithelium. Furthermore, the quantities of lysozyme in bronchial fluids was correlated with the size of the bronchial preparations. These results suggest that the lysozyme was principally secreted by the human bronchi (submucosal layer rather than by parenchyma tissues and that a greater release was observed in the proximal airways.

  6. Petrophysical evaluation methods: basal quartz formation, Manyberries Area , Alberta

    Energy Technology Data Exchange (ETDEWEB)

    Davis, B.W.

    1980-01-01

    Hydrocarbons, both oil and gas, have been discovered in the basal quartz formation in the Manyberries area of SE Alberta. Estimation of producible fluids and hydrocarbons in place has been difficult due to the very shaly nature of the reservoir rock. Calculations of water saturation with no corrections for clay conductivity underestimates the hydrocarbons in place. The Waxman-Smits evaluation technique, which provides a method to account for clay conductivities, was used to estimate water saturation based on total porosity. Work of other authors provides a technique to correlate total and effective porosities. This was used to estimate effective porosity and subsequently water saturation based on the effective porosity. Error analysis was undertaken to estimate the uncertainty in the calculated water saturations.

  7. Desalination of Basal Water by Mesoporous Carbons Nanocomposite Membrane.

    Science.gov (United States)

    Choi, Jeongdong; Ahn, Youngho; Gamal El-Din, Mohamed; Kim, Eun-Sik

    2016-02-01

    The hydro-transportation process used to obtain bitumen from the Alberta oil sands produces large volume of basal depressurization water (BDW), which contains high salt concentrations. In this research, thin-film nanocomposite (TFN) membrane technology applied to treat BDW in lab-scale, and evaluated water properties before and after the treatment. The average rejection ratios of ionic species were 95.2% and 92.8% by TFN membrane (with ordered mesoporous carbons (OMCs)) and thin-film composite (TFC) (without OMCs) membrane, respectively. The turbidity and total dissolved solids (TDS) were completely rejected in all treatment conditions. Interestingly, the water flux of TFN membrane was dramatically increased compared to TFC membrane. The increase of water flux was believed to be caused by the increased membrane surface hydrophilicity and nano-pore effects by the OMCs.

  8. Redefinition and global estimation of basal ecosystem respiration rate

    DEFF Research Database (Denmark)

    Yuan, Wenping; Luo, Yiqi; Li, Xianglan;

    2011-01-01

    Basal ecosystem respiration rate (BR), the ecosystem respiration rate at a given temperature, is a common and important parameter in empirical models for quantifying ecosystem respiration (ER) globally. Numerous studies have indicated that BR varies in space. However, many empirical ER models still...... use a global constant BR largely due to the lack of a functional description for BR. In this study, we redefined BR to be ecosystem respiration rate at the mean annual temperature. To test the validity of this concept, we conducted a synthesis analysis using 276 site-years of eddy covariance data...... use efficiency GPP model (i.e., EC-LUE) was applied to estimate global GPP, BR and ER with input data from MERRA (Modern Era Retrospective-Analysis for Research and Applications) and MODIS (Moderate resolution Imaging Spectroradiometer). The global ER was 103 Pg C yr −1, with the highest respiration...

  9. Basal ganglia calcification as a putative cause for cognitive decline

    Directory of Open Access Journals (Sweden)

    João Ricardo Mendes de Oliveira

    Full Text Available ABSTRACT Basal ganglia calcifications (BGC may be present in various medical conditions, such as infections, metabolic, psychiatric and neurological diseases, associated with different etiologies and clinical outcomes, including parkinsonism, psychosis, mood swings and dementia. A literature review was performed highlighting the main neuropsychological findings of BGC, with particular attention to clinical reports of cognitive decline. Neuroimaging studies combined with neuropsychological analysis show that some patients have shown progressive disturbances of selective attention, declarative memory and verbal perseveration. Therefore, the calcification process might represent a putative cause for dementia syndromes, suggesting a probable link among calcinosis, the aging process and eventually with neuronal death. The increasing number of reports available will foster a necessary discussion about cerebral calcinosis and its role in determining symptomatology in dementia patients

  10. A basal tyrannosauroid dinosaur from the Late Jurassic of China.

    Science.gov (United States)

    Xu, Xing; Clark, James M; Forster, Catherine A; Norell, Mark A; Erickson, Gregory M; Eberth, David A; Jia, Chengkai; Zhao, Qi

    2006-02-01

    The tyrannosauroid fossil record is mainly restricted to Cretaceous sediments of Laurasia, although some very fragmentary Jurassic specimens have been referred to this group. Here we report a new basal tyrannosauroid, Guanlong wucaii gen. et sp. nov., from the lower Upper Jurassic of the Junggar Basin, northwestern China. G. wucaii is the oldest known tyrannosauroid and shows several unexpectedly primitive pelvic features. Nevertheless, the limbs of G. wucaii share several features with derived coelurosaurs, and it possesses features shared by other coelurosaurian clades. This unusual combination of character states provides an insight into the poorly known early radiation of the Coelurosauria. Notably, the presumed predatory Guanlong has a large, fragile and highly pneumatic cranial crest that is among the most elaborate known in any non-avian dinosaur and could be comparable to some classical exaggerated ornamental traits among vertebrates.

  11. Favourable results of Mohs micrographic surgery for basal cell carcinoma

    DEFF Research Database (Denmark)

    Gniadecki, Robert; Glud, Martin; Mortensen, Kia

    2015-01-01

    was 66.1 years. The most common localisations were the forehead (31.3%), the nose (31.0%) and the cheek (14.7%). Primary BCC comprised 54.0%; the remaining cases were relapses, most frequently after curettage (36.9%), radiotherapy (18.9%) and photodynamic therapy (11.7%). MMS leads to 40% smaller skin......INTRODUCTION: Basal cell carcinoma (BCC) is the most common malignant neoplasm with an annual incidence approaching 200/100,000 person-years. Mohs micrographic surgery (MMS) is widely used in North America and in Europe for treatment of BCC. This technique ensures radical tumour removal, sparing...... of the surrounding healthy skin, and it also offers higher cure rates than standard tumour excision with a predefined margin of healthy skin. The superiority of MMS relies on the fact that the entire (100%) margin of the excised tissue is examined microscopically for residual tumour in contrast to the traditional...

  12. Basal lamina structural alterations in human asymmetric aneurismatic aorta

    Directory of Open Access Journals (Sweden)

    M Cotrufo

    2009-06-01

    Full Text Available Basal lamina (BL is a crucial mechanical and functional component of blood vessels, constituting a sensor of extracellular microenvironment for endothelial cells and pericytes. Recently, an abnormality in the process of matrix microfibrillar component remodeling has been advocated as a mechanism involved in the development of aortic dilation.We focused our attention on BL composition and organization and studied some of the main components of the Extracellular Matrix such as Tenascin, Laminins, Fibronectin, type I, III and IV Collagens.We used surgical fragments from 27 patients, submitted to operation because of aortic root aneurysm and 5 normal aortic wall specimens from heart donors without any evidence for aneurysmal or atherosclerotic diseases of the aorta. Two samples of aortic wall were harvested from each patient, proximal to the sinotubular junction at the aortic convexity and concavity. Each specimen was processed both for immunohistochemical examination and molecular biology study.We compared the convexity of each aortic sample with the concavity of the same vessel, and both of them with the control samples. The synthesis of mRNA and the levels of each protein were assessed, respectively, by RTPCR and Western Blot analysis. Immunohistochemistry elucidated the organization of BL, whose composition was revealed by molecular biology. All pathological samples showed a wall thinner than normal ones. Basal lamina of the aortic wall evidentiated important changes in the tridimensional arrangement of its major components which lost their regular arrangement in pathological specimens. Collagen I, Laminin a2 chain and Fibronectin amounts decreased in pathological samples, while type IV Collagen and Tenascin synthesis increased. Consistently with the common macroscopic observation that ascending aorta dilations tend to expand asymmetrically, with prevalent involvement of the vessel convexity and relative sparing of the concavity, Collagen type

  13. Auditory cortex basal activity modulates cochlear responses in chinchillas.

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    Alex León

    Full Text Available BACKGROUND: The auditory efferent system has unique neuroanatomical pathways that connect the cerebral cortex with sensory receptor cells. Pyramidal neurons located in layers V and VI of the primary auditory cortex constitute descending projections to the thalamus, inferior colliculus, and even directly to the superior olivary complex and to the cochlear nucleus. Efferent pathways are connected to the cochlear receptor by the olivocochlear system, which innervates outer hair cells and auditory nerve fibers. The functional role of the cortico-olivocochlear efferent system remains debated. We hypothesized that auditory cortex basal activity modulates cochlear and auditory-nerve afferent responses through the efferent system. METHODOLOGY/PRINCIPAL FINDINGS: Cochlear microphonics (CM, auditory-nerve compound action potentials (CAP and auditory cortex evoked potentials (ACEP were recorded in twenty anesthetized chinchillas, before, during and after auditory cortex deactivation by two methods: lidocaine microinjections or cortical cooling with cryoloops. Auditory cortex deactivation induced a transient reduction in ACEP amplitudes in fifteen animals (deactivation experiments and a permanent reduction in five chinchillas (lesion experiments. We found significant changes in the amplitude of CM in both types of experiments, being the most common effect a CM decrease found in fifteen animals. Concomitantly to CM amplitude changes, we found CAP increases in seven chinchillas and CAP reductions in thirteen animals. Although ACEP amplitudes were completely recovered after ninety minutes in deactivation experiments, only partial recovery was observed in the magnitudes of cochlear responses. CONCLUSIONS/SIGNIFICANCE: These results show that blocking ongoing auditory cortex activity modulates CM and CAP responses, demonstrating that cortico-olivocochlear circuits regulate auditory nerve and cochlear responses through a basal efferent tone. The diversity of the

  14. The nervous systems of basally branching nemertea (palaeonemertea.

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    Patrick Beckers

    Full Text Available In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  15. The nervous systems of basally branching nemertea (palaeonemertea).

    Science.gov (United States)

    Beckers, Patrick; Loesel, Rudi; Bartolomaeus, Thomas

    2013-01-01

    In recent years, a lot of studies have been published dealing with the anatomy of the nervous system in different spiralian species. The only nemertean species investigated in this context probably shows derived characters and thus the conditions found there are not useful in inferring the relationship between nemerteans and other spiralian taxa. Ingroup relationships within Nemertea are still unclear, but there is some agreement that the palaeonemerteans form a basal, paraphyletic grade. Thus, palaeonemertean species are likely the most informative when comparing with other invertebrate groups. We therefore analyzed the nervous system of several palaeonemertean species by combining histology and immunostaining. 3D reconstructions based on the aligned slices were performed to get an overall impression of the central nervous system, and immunohistochemistry was chosen to reveal fine structures and to be able to compare the data with recently published results. The insights presented here permit a first attempt to reconstruct the primary organization of the nemertean nervous system. This comparative analysis allows substantiating homology hypotheses for nerves of the peripheral nervous system. This study also provides evidence that the nemertean brain primarily consists of two lobes connected by a strong ventral commissure and one to several dorsal commissures. During nemertean evolution, the brain underwent continuous compartmentalization into a pair of dorsal and ventral lobes interconnected by commissures and lateral tracts. Given that this conclusion can be corroborated by cladistic analyses, nemerteans should share a common ancestor with spiralians that primarily have a simple brain consisting of paired medullary, frontally commissurized and reinforced cords. Such an organization resembles the situation found in presumably basally branching annelids or mollusks.

  16. COMPARATIVE ANATOMICAL STUDIES ABOUT CHICKEN SUB-BASAL CONNECTIONS

    Directory of Open Access Journals (Sweden)

    CARMEN BERGHES

    2013-07-01

    Full Text Available The studies aimed to describe the nervous formations from the base of the cranium in the hen and domestic duck. These clarifications are necessary in order to disclose some unknown facts regarding this region in the poultry species used preponderantly in laboratory studies of the aviary flu. The vegetative connections from the base of the skull have been studied on 10 poultry specimens, 5 hens and 5 ducks. The animals have been euthanatized using chloroform and a special dye has been injected through the heart in order to achieve a better differentiation of the nervous formations. Dissection was performed under a magnifying glass using instruments adequate to highly fine dissections. Photos and sketches of the dissected pieces have been taken. Nomina Anatomica (2003 was used to describe the observed formations.The studies showed that the cranial cervical ganglia around which is the sub-basal nervous tissue, is located on the border of the occipital hole, at the basis of the temporal pyramid, much deeper than in mammalians; it is better developed in the duck (3-4 mm than in the hen (1-2 mm; the cranial cervical ganglia has the shape of a globe in gallinaceans and it is long in shape in the ducks. A multitude of connecting branches were observed around the lymph node, linking it to the vague nerve, to the hypoglossal nerve, to the glossopharyngeal nerve and to the transversal paravertebral chain which is specific to poultry; an obvious branch detaches from the cranial pole, which is the sub-basal connective, while the cervical connective detaches from the caudal pole, connecting it to the cervical-thoracic lymph node.

  17. Effect of genistein on basal jejunal chloride secretion in R117H CF mice is sex and route specific

    Directory of Open Access Journals (Sweden)

    Rayyan E

    2015-01-01

    -mediated difference among the groups. Serum levels of genistein were significantly elevated, compared to respective controls, by either 600Gd (equally elevated in males and females or 600Gi (elevated more in females versus males. These data suggest a sex-dependent increase in basal Isc of R117H mice and that the increase is also specific for route of administration.Keywords: genistein, intestine, secretion, CFTR, R117H

  18. Clinical observation on treating vertebral compression fractures by magnetic therapy plus salmon calcitonin%磁疗法配合鲑降钙素治疗腰椎压缩性骨折的临床疗效

    Institute of Scientific and Technical Information of China (English)

    甘春正

    2015-01-01

    目的:探讨磁疗法配合鲑降钙素治疗腰椎压缩性骨折的临床疗效。方法:选取我院骨科门诊2013年4月-2014年2月收治的腰椎压缩性骨折患者100例,均采用磁疗法配合鲑降钙素治疗,并对其疗效进行观察和分析。结果:接受磁疗法配合鲑降钙素治疗的100例患者治疗15d,89例痊愈,11例好转,有效率为100%。因此采用磁疗法配合鲑降钙素治疗腰椎压缩性骨折,疗效显著,患者安全有效、易推广,与手术相比,避免了由于手术带来的风险及并发症,减轻患者的痛苦和负担,值得在临床推广应用。%Objective: To discuss clinical effects of magnetic therapy plus salmon calcitonin on vertebral compression fractures. Methods: 100 patients were given magnetic therapy plus salmon calcitonin, and clinical effects were observed and analyzed. Results: After 15 days of treatment, in 100 patients, 89 cases were cured, 11 cases were improved, the efficiency was 100%. Clinical efficacy of magnetic therapy plus salmon calcitonin was confirmed and safe. Compared with operation, magnetic therapy plus salmon calcitonin could avoid the risks and complications, reduce patient pain and burden, and were worthy of clinical application.

  19. A Novel Basal Body Protein That Is a Polo-like Kinase Substrate Is Required for Basal Body Segregation and Flagellum Adhesion in Trypanosoma brucei.

    Science.gov (United States)

    Hu, Huiqing; Zhou, Qing; Li, Ziyin

    2015-10-01

    The Polo-like kinase (PLK) in Trypanosoma brucei plays multiple roles in basal body segregation, flagellum attachment, and cytokinesis. However, the mechanistic role of TbPLK remains elusive, mainly because most of its substrates are not known. Here, we report a new substrate of TbPLK, SPBB1, and its essential roles in T. brucei. SPBB1 was identified through yeast two-hybrid screening with the kinase-dead TbPLK as the bait. It interacts with TbPLK in vitro and in vivo, and is phosphorylated by TbPLK in vitro. SPBB1 localizes to both the mature basal body and the probasal body throughout the cell cycle, and co-localizes with TbPLK at the basal body during early cell cycle stages. RNAi against SPBB1 in procyclic trypanosomes inhibited basal body segregation, disrupted the new flagellum attachment zone filament, detached the new flagellum, and caused defective cytokinesis. Moreover, RNAi of SPBB1 confined TbPLK at the basal body and the bilobe structure, resulting in constitutive phosphorylation of TbCentrin2 at the bilobe. Altogether, these results identified a basal body protein as a TbPLK substrate and its essential role in promoting basal body segregation and flagellum attachment zone filament assembly for flagellum adhesion and cytokinesis initiation.

  20. Oral Zinc Supplementation Decreases the Serum Iron Concentration in Healthy Schoolchildren: A Pilot Study

    Directory of Open Access Journals (Sweden)

    Naira Josele Neves de Brito

    2014-09-01

    Full Text Available The recognized antagonistic actions between zinc and iron prompted us to study this subject in children. A convenience sample was used. Thirty healthy children between 8 and 9 years of age were studied with the aim of establishing the effect of a 3-mo oral zinc supplementation on iron status. Fifteen individuals were given a placebo (control group, and 15 were given 10 mg Zn/day (experimental group. Blood samples were collected at 0, 60, 120, 180 and 210 min after a 12-h overnight fast, before and after placebo or zinc supplementation. This supplementation was associated with significant improvements in energy, protein, fat, carbohydrate, fiber, calcium, iron, and zinc intake in accordance with the recommendations for age and sex. The basal serum zinc concentration significantly increased after oral zinc supplementation (p < 0.001. However, basal serum iron concentrations and area under the iron curves significantly decreased in the experimental group (p < 0.0001 and remained at the same level throughout the 210-min study. The values obtained for hemoglobin, mean corpuscular volume, ferritin, transferrin, transferrin saturation, ceruloplasmin and total protein were within normal reference ranges. In conclusion, the decrease in serum iron was likely due to the effects of chronic zinc administration, and the decrease in serum iron was not sufficient to cause anemia.