Central Precocious Puberty: Adult Height in Girls Treated with Quarterly or Monthly Gonadotropin-Releasing Hormone Analog Triptorelin.

PubMed

Bertelloni, Silvano; Massart, Francesco; Einaudi, Silvia; Wasniewska, Malgorzata; Miccoli, Mario; Baroncelli, Giampiero I

2015-01-01

Treatment with quarterly gonadotropin-releasing hormone (GnRH) analogs may improve compliance and optimize outcome in girls with central precocious puberty (CPP), but long-term comparative data between the new and the monthly formulations are very scarce. A group of girls with idiopathic CPP (n = 13; age 7.9 ± 0.6 years) were treated from the beginning with quarterly triptorelin (11.25 mg/90 days) and followed up to the achievement of adult height (AH). A group of girls with idiopathic CPP (n = 12; age 8.0 ± 0.6 years) treated with monthly triptorelin (3.75 mg/28 days) served as controls. The AH (157.1 ± 4.9 cm) of girls treated with quarterly triptorelin was not significantly different from their mid-parental height (159.7 ± 3.8 cm) and significantly increased in comparison with predicted AH (average tables) at the beginning of GnRH analog therapy. The AH of girls treated with quarterly triptorelin was not significantly different in comparison with that of girls treated with the monthly formulation (158.1 ± 6.6 cm; mid-parental height 158.4 ± 5.0 cm). Treatment with quarterly triptorelin formulation permitted to achieve an AH adequate for mid-parental height in girls with CPP. Significant differences of AH between girls with CPP treated with quarterly or monthly formulations were not found. © 2015 S. Karger AG, Basel.

Treatment of central precocious puberty with triptorelin 11.25 mg depot formulation.

PubMed

Martínez-Aguayo, A; Hernández, M I; Beas, F; Iñiguez, G; Avila, A; Sovino, H; Bravo, E; Cassorla, F

2006-08-01

A new triptorelin 11.25 mg long depot formulation is now available for the treatment of central precocious puberty (CPP). The aim of our study was to evaluate the efficacy of triptorelin 11.25 mg administered every 90 days to suppress gonadotropin and sex steroid secretion and pubertal signs in children with CPP during 2 years of treatment. Inclusion criteria were clinical pubertal development before the age of 8 years in girls or 9 years in boys, advanced bone age and a pubertal LH response (peak >5 mIU/ml) to GnRH. We studied 20 patients (19 girls and 1 boy), with a median age at entry into the study of 7.5 +/- 0.2 years for girls, and 9 years for the boy. The basal and GnRH-stimulated serum levels of LH and FSH decreased significantly from baseline to 3 months of therapy (p <0.0001). All patients had a GnRH-stimulated peak below 3 mIU/ml between 6 and 24 months of treatment. The pituitary-gonadal axis recovered adequately after discontinuation of therapy. These results suggest that 3-month depot triptorelin is a satisfactory alternative for the therapy of children with CPP. The longer interval between injections may increase acceptability and compliance with treatment.

Results of a second year of therapy with the 12-month histrelin implant for the treatment of central precocious puberty.

PubMed

Rahhal, Samar; Clarke, William L; Kletter, Gad B; Lee, Peter A; Neely, E Kirk; Reiter, Edward O; Saenger, Paul; Shulman, Dorothy; Silverman, Lawrence; Eugster, Erica A

2009-01-01

Background. Gonadotropin releasing hormone analogs (GnRHas) are standard of care for central precocious puberty (CPP). The histrelin subcutaneous implant is safe and effective in the treatment of CPP for one year. Objective. The study evaluates a second year of therapy in children with CPP who received a new implant after one year of treatment. Methods. A prospective one-year study following an initial 12-month treatment period was conducted. Results. Thirty-one patients (29 girls) aged 7.7 +/- 1.5 years received a second implant. Eighteen were naïve to GnRHa therapy at first implantation. Peak LH declined from 0.92 +/- 0.58 mIU/mL at 12 months to 0.51 +/- 0.33 mIU/mL at 24 months (P < .0001) in naïve subjects, and from 0.74 +/- 0.50 mIU/mL at 12 months to 0.45 +/- 0.35 mIU/mL at 24 months (P = .0081) in previously treated subjects. Predicted adult height increased by 5.1 cm at 24 months (P = .0001). Minor implant site reactions occurred in 61%, while minor difficulties with explantation occurred in 32.2% of subjects. Conclusion. The histrelin implant demonstrates profound hypothalamic-pituitary-gonadal axis suppression when a new implant is placed for a second year of treatment. Prospective follow-up of this therapeutic modality for the treatment of CPP is needed.

Assessment of Estradiol Response after Depot Triptorelin Administration in Girls with Central Precocious Puberty.

PubMed

Freire, Analía Verónica; Gryngarten, Mirta Graciela; Ballerini, María Gabriela; Arcari, Andrea Josefina; Escobar, María Eugenia; Bergadá, Ignacio; Ropelato, María Gabriela

2016-01-01

Estradiol at baseline or after a classical gonadotropin-releasing hormone test did not reflect ovarian steroidogenesis in central precocious puberty (CPP) girls. To evaluate estradiol response to depot triptorelin, both at start and during therapy to determine how active ovarian steroidogenesis is at pubertal stage and under therapy. A prospective study was performed in 43 CPP girls. Serum luteinizing hormone and follicle-stimulating hormone at 3 h (LH-3h, FSH-3h) and estradiol at 24 h (E2-24h) after injection of depot triptorelin 3.75 mg were measured, at first dose and at 3, 6, 12, 18 and 24 months of treatment. E2-24h after depot triptorelin was >100 pg/ml after the first dose. Estradiol response (E2-24h) fell to levels <14 pg/ml in 78 out of 82 follow-up visits along 2 years of therapy. Concomitantly, LH-3h and FSH-3h were <4.0 and <6.3 IU/l, respectively. In 4 patients with inadequate treatment, E2-24h, LH-3h and FSH-3h rose to pubertal values similar to those observed at first dose. Estradiol (<14 pg/ml) assessment 24 h after depot triptorelin administration is a reliable and simple manner to confirm ovarian suppression in CPP girls during treatment. © 2015 S. Karger AG, Basel.

Final height in central precocious puberty after long term treatment with a slow release GnRH agonist.

PubMed Central

Oostdijk, W; Rikken, B; Schreuder, S; Otten, B; Odink, R; Rouwé, C; Jansen, M; Gerver, W J; Waelkens, J; Drop, S

1996-01-01

OBJECTIVE: To study the resumption of puberty and the final height achieved in children with central precocious puberty (CPP) treated with the GnRH agonist triptorelin. PATIENTS: 31 girls and five boys with CPP who were treated with triptorelin 3.75 mg intramuscularly every four weeks. Girls were treated for a mean (SD) of 3.4 (1.0) years and were followed up for 4.0 (1.2) years after the treatment was stopped. RESULTS: The rate of bone maturation decreased during treatment and the predicted adult height increased from 158.2 (7.4) cm to 163.9 (7.5) cm at the end of treatment (p < 0.001). When treatment was stopped bone maturation accelerated, resulting in a final height of 161.6 (7.0) cm, which was higher than the predicted adult height at the start of treatment (p < 0.001). Height at the start of treatment was the most important factor positively influencing final height (r = 0.75, p < 0.001). Bone age at cessation of treatment negatively influenced final height (r = -0.52, p = 0.03). A negative correlation between bone age and height increment after discontinuation of treatment was observed (r = -0.85, p = 0.001). Residual growth capacity was optimal when bone age on cessation of treatment was 12 to 12.5 years. Body mass index increased during treatment and remained high on cessation. At final height, the ratio of sitting height to subischial leg length was normal. Menarche occurred at 12.3 (1.1) years, and at a median (range) of 1.1 (0.4 to 2.6) years after treatment was stopped. The ovaries were normal on pelvic ultrasonography. CONCLUSIONS: Treatment of CPP with triptorelin increases final height, with normal body proportions, and seems to increase body mass index. The best results were achieved in girls who were taller at the start of treatment. Puberty was resumed after treatment, without the occurrence of polycystic ovaries. PMID:8984913

Three-month sustained-release triptorelin (11.25 mg) in the treatment of central precocious puberty.

PubMed

Carel, Jean-Claude; Blumberg, Joëlle; Seymour, Christine; Adamsbaum, Catherine; Lahlou, Najiba

2006-01-01

Depot GnRH agonists are commonly used in the treatment of central precocious puberty (CPP). The triptorelin 11.25 mg 3-month depot, currently used in adult indications, had not previously been evaluated in CPP. This was a multicenter, open-label, 12 month trial conducted in 64 CPP children (54 girls and 10 boys), treated quarterly. Children with a clinical onset of pubertal development before the age of 8 years (girls) or 9 years (boys), pubertal response of LH to GnRH > or = 7 IU/l, advanced bone age > 1 year, enlarged uterus (> or = 36 mm) and testosterone level > or = 0.5 ng/ml (boys), were included. Suppression of gonadotropic activation, as determined from serum LH, FSH, estradiol or testosterone, and pubertal signs were assessed at Months 3, 6 and 12. GnRH-stimulated peak LH < or = 3 IU/l, the main efficacy criterion, was met in 53 out of 62 (85%), 60 out of 62 (97%) and 56 out of 59 (95%) of the children at Months 3, 6 and 12 respectively. Serum FSH and sex steroids were also significantly reduced, while pubertal development regressed in most patients. Mean residual triptorelin levels were stable from Month 3 through to Month 12. The triptorelin 3-month depot was well tolerated. Severe injection pain was experienced in only one instance. Five girls experienced mild-to-moderate or severe (one girl) withdrawal bleeding. The triptorelin 3-month depot efficiently suppresses the pituitary-gonadal axis and pubertal development in children with CPP. This formulation allows a 3-fold reduction, over the once-a-month depot, in the number of i.m. injections required each year.

Quantitative calcaneal ultrasound parameters and bone mineral density at final height in girls treated with depot gonadotrophin-releasing hormone agonist for central precocious puberty or idiopathic short stature.

PubMed

Kapteijns-van Kordelaar, Simone; Noordam, Kees; Otten, Barto; van den Bergh, Joop

2003-11-01

To evaluate the effect of gonadotrophin-releasing hormone (GnRH) agonist treatment on bone quality at final height, we studied girls with central precocious puberty (CPP) and with idiopathic short stature (ISS). A total of 25 Caucasian girls were included: group A (n=14) with idiopathic CPP (mean age at start 7.4 years) and group B (n=11) with ISS (mean age at start 11.7 years). Treatment duration was 3.8 and 1.7 years respectively. The quantitative ultrasound parameters (QUS) broadband ultrasound attenuation (BUA) and speed of sound (SOS) were measured at the calcaneus (UBIS 3000 device). Lumbar spine bone mineral density (BMD; L2-L4) was measured by dual energy X-ray absorptiometry (DXA) (Hologic QDR1000). Measurements were performed at final height and expressed as Z-scores corrected for bone age. Mean Z-scores of QUS parameters, areal BMD and volumetric BMD (BMDvol) were above -1 in both groups (group A: BUA Z-score -0.21, SOS Z-score -0.29, BMD Z-score 0.02, BMDvol Z-score 0.05, group B: BUA Z-score -0.93, SOS Z-score -0.40, BMD Z-score -0.86, BMDvol Z-score -0.68), although mean Z-scores of BUA and areal BMD in group B were significantly different from zero (P=0.03 and P=0.02 respectively). Mean Z-score BMDvol was not significantly different from zero (P=0.05), we found no significant difference between the groups for BMDvol (P=0.13). Although quantitative ultrasound parameters parameters and bone mineral density were normal in girls with central precocious puberty at final height after gonadotrophin-releasing hormone agonist treatment, mean Z-score for broadband ultrasound attenuation and areal bone mineral density were significantly different from zero and mean Z-score for volumetric bone mineral density was (just) not significantly different from zero in idiopathic short stature girls with normal puberty treated with gonadotrophin-releasing hormone agonists. Therefore we cannot say that this treatment is safe in these girls with regard to bone health.

[Hand and wrist bone maturation in children with central precocious puberty and idiopathic short stature].

PubMed

Wang, Anru; Yang, Fangling; Yu, Baosheng; Shan, Ye; Gao, Lanying; Zhang, Xiaoxiao; Peng, Ya

2013-07-01

To investigate the maturation of individual bones on the hand and wrist in children with central precocious puberty (CPP) and idiopathic short stature (ISS). Hand and wrist films of 25 children with CPP, 29 children with ISS and 21 normal controls were evaluated by conventional Greulich-Pyle (GP) atlas method and individual bone assessment method, in which all twenty bones of the hand and wrist were evaluated based on GP atlas, including 2 radius and ulna, 7 carpal bones, 11 metacarpal and phalangeal bones, the average bone age (BA) was calculated. The differences in groups were analyzed by independent samples t test. The differences between the two methods were analyzed by paired sample t test. The differences between BA and chronological age (CA) were analyzed by ROC with SPSS 17.0. Compared with the normal control group, the advance of BA in the CPP group was 0.70-2.26 y (1.48 ±0.78) by the GP atlas method, while that was 0.28-2.00 y(1.14 ±0.86) by the individual bone evaluation method. In all twenty bones, the advance of metacarpal and phalangeal BA was the greatest [0.34-2.06 y(1.2±0.86)]. In the ISS group,the delay of BA was 0.47-2.91 y(-1.69±1.22) by the GP atlas method, while that was 0.48-2.50 y (-1.49±1.01) by individual bone evaluation method.The delay of carpal BA was the greatest [0.59-2.73 y(-1.66±1.07)] in all twenty bones. In the ISS group and the normal control group, there were no statistic differences between the two methods. In the CPP group, statistic difference was found between two methods. There were no statistic differences for the areas under ROC curves between two methods. The advance of metacarpal and phalangeal BA is the greatest in CPP group and the delay of carpal BA is the greatest in ISS group.Both methods provide diagnostic information for bone age in CPP and ISS children.

Body mass index and body composition in adolescents treated with gonadotropin-releasing hormone analogue triptorelin depot for central precocious puberty: data at near final height.

PubMed

Chiocca, Elena; Dati, Eleonora; Baroncelli, Giampiero I; Mora, Stefano; Parrini, Donatella; Erba, Paola; Bertelloni, Silvano

2009-01-01

In children with central precocious puberty (CPP), gonadotropin-releasing hormone (GnRH) analogue treatment has been associated with an increase in body mass index (BMI). We evaluated BMI and body composition in adolescents treated with GnRH analogue at their near final height to assess the long-term effects of therapy on these parameters. We studied 20 patients (14.8 +/- 1.6 years; 17 females) previously treated with triptorelin depot for CPP (3.75 mg/28 days) from 8.1 +/- 0.8 to 11.5 +/- 0.8 years. 23 healthy adolescents with normal onset of puberty (14.7 +/- 2.1 years, 19 females) were the controls. BMI and body composition (dual-energy x-ray absorptiometry) were assessed. Patients reached their near adult height (-0.5 +/- 1.1 standard deviation score (SDS)); the girls were menstruating and the majority (15/17) had regular cycles, the boys showed normal testicular function. BMI was unchanged from the start of GnRH analogue therapy (0.4 +/- 1.0 SDS) to near adult height (0.2 +/- 1.0 SDS, p = NS vs. 0). Total fat mass (TFM) was significantly increased (16,144 +/- 8,065 g; controls 10,712.1 +/- 4,120.4 g, p < 0.02); glucose homeostasis and lipid profile corresponded to reference ranges. GnRH analogue therapy did not show long-term detrimental effects on BMI, but it may increase TFM, suggesting that body composition should be monitored till adulthood. Copyright 2009 S. Karger AG, Basel.

Use of a potent, long acting agonist of gonadotropin-releasing hormone in the treatment of precocious puberty.

PubMed

Boepple, P A; Mansfield, M J; Wierman, M E; Rudlin, C R; Bode, H H; Crigler, J F; Crawford, J D; Crowley, W F

1986-02-01

Studies utilizing the administration of GnRH in various GnRH-deficient models have revealed the critical importance of the dose and mode of delivery of this releasing factor in determining the subsequent pituitary response. Chronic administration of long acting GnRH agonists (GnRHa), like continuous infusion of high doses of the native peptide, results in suppression of pituitary gonadotropin secretion. This selective and reversible suppression of gonadotropin secretion suggested several therapeutic applications for these analogs, particularly in the treatment of central precocious puberty (CPP), a disorder for which the previously available therapies lacked uniform efficacy and were associated with potential side effects. In our series, 74 children with CPP have been treated during the last 5 yr with the potent GnRH agonist, [D-Trp6, Pro9-ethylamide(NEt)]GnRH. Having selected a dose and route of administration that produced uniform suppression of spontaneous and stimulated pituitary gonadotropin secretion, GnRHa therapy resulted in a fall of gonadal sex steroid levels into the prepubertal range, a halting or regression of secondary sexual development, and a complete cessation of menses. Growth velocity slowed during therapy, with this slowing more pronounced during prolonged treatment periods and among those patients with more advanced chronological and skeletal ages. Skeletal maturation was retarded to a greater degree than linear growth, with resultant increases in the predictions for adult stature. Moreover, these benefits have been achieved in the absence of significant side effects. Complete reversal of the suppression of gonadarche has followed discontinuation of therapy; however, patterns of growth and skeletal maturation after discontinuation of GnRHa administration remain to be characterized. Thus, the impact of GnRHa therapy on final height must await further longitudinal study. The selective nature of GnRHa suppression of gonadarche also permits an investigation of the natural history of adrenarche and its discrete influences upon skeletal growth and maturation. In addition, GnRHa therapy of CPP provides a unique opportunity to study the effects of gonadal sex steroids on GH secretion and somatomedin-C (Sm-C) generation during sexual maturation. Finally, the detailed characterization of children with precocious puberty has helped to define more precisely a subset of patients whose precocity occurs in the absence of demonstrable gonadotropin secretion.(ABSTRACT TRUNCATED AT 400 WORDS)

BIRD’S-EYE VIEW OF GnRH ANALOG USE IN A PEDIATRIC ENDOCRINOLOGY REFERRAL CENTER

PubMed Central

Watson, Sara E.; Greene, Ariana; Lewis, Katherine; Eugster, Erica A.

2017-01-01

Objective Gonadotropin-releasing hormone analogs (GnRHa) are standard of care for the treatment of central precocious puberty (CPP). GnRHa have also been prescribed in other clinical settings with the hope of increasing adult stature, although evidence to support this practice is lacking. The degree to which GnRHa are being prescribed for indications other than CPP in routine clinical care has not been described. We sought to systematically examine GnRHa prescribing practices among the pediatric endocrinologists at our academic medical center. Methods We reviewed medical records of children treated with GnRHa during a 6-year interval. Variables analyzed included gender, age at start of treatment, indication for therapy, and use of growth hormone as adjunctive treatment. Nonparametric analyses were utilized to compare treatment characteristics of those with CPP versus those without. Results A total of 260 patients (82% female) aged 8.06 ± 2.68 years were identified. Of these, 191 (73.5%) were treated for CPP, whereas 69 (26.5%) were treated for normally timed puberty in the context of idiopathic short stature/poor predicted height (n = 37), growth hormone deficiency (n = 17), congenital adrenal hyperplasia (n = 10), primary hypothyroidism (n = 4), and developmental delay (n = 1). Of the 161 girls with CPP, GnRHa therapy was initiated at ≥8 years of age in 62 (39%). Conclusion Whereas most patients were treated for CPP, ~27% were treated for other indications. Of girls with CPP, 39% were treated at an age when benefit in terms of height is unlikely. This highlights the need for rigorous studies of GnRHa use for indications beyond CPP. PMID:25667370

Change in body mass index and insulin resistance after 1-year treatment with gonadotropin-releasing hormone agonists in girls with central precocious puberty.

PubMed

Park, Jina; Kim, Jae Hyun

2017-03-01

Gonadotropin-releasing hormone agonist (GnRHa) is used as a therapeutic agent for central precocious puberty (CPP); however, increased obesity may subsequently occur. This study compared body mass index (BMI) and insulin resistance during the first year of GnRHa treatment for CPP. Patient group included 83 girls (aged 7.0-8.9 years) with developed breasts and a peak luteinizing hormone level of ≥5 IU/L after GnRH stimulation. Control group included 48 prepubertal girls. BMI and insulin resistance-related indices (homeostasis model assessment of insulin resistance [HOMA-IR] and quantitative insulin sensitivity check index [QUICKI]) were used to compare the groups before treatment, and among the patient group before and after GnRHa treatment. No statistical difference in BMI z -score was detected between the 2 groups before treatment. Fasting insulin and HOMA-IR were increased in the patient group; fasting glucose-to-insulin ratio and QUICKI were increased in the control group (all P <0.001). In normal-weight subjects in the patient group, BMI z -score was significantly increased during GnRHa treatment (-0.1±0.7 vs. 0.1±0.8, P <0.001), whereas HOMA-IR and QUICKI exhibited no differences. In overweight subjects in the patient group; BMI z -score and HOMA-IR were not significantly different, whereas QUICKI was significantly decreased during GnRHa treatment (0.35±0.03 vs. 0.33±0.02, P =0.044). Girls with CPP exhibited increased insulin resistance compared to the control group. During GnRHa treatment, normal-weight individuals showed increased BMI z -scores without increased insulin resistance; the overweight group demonstrated increased insulin resistance without significantly altered BMI z -scores. Long-term follow-up of BMI and insulin resistance changes in patients with CPP is required.

A 6-Month Trial of the Efficacy and Safety of Triptorelin Pamoate (11.25 mg) Every 3 Months in Children with Precocious Puberty: A Retrospective Comparison with Triptorelin Acetate.

PubMed

Zenaty, Delphine; Blumberg, Joelle; Liyanage, Nilani; Jacqz-Aigrain, Evelyne; Lahlou, Najiba; Carel, Jean-Claude

2016-01-01

To evaluate the efficacy and safety of a triptorelin pamoate (11.25 mg) 3-month formulation in the management of central precocious puberty (CPP) (TP Study) and to retrospectively compare it with a triptorelin acetate (11.25 mg) 3-month formulation (TA Study). We conducted two phase III, multicentre, single-stage, non-comparative, open-label studies. In the TP Study, patients with CPP received an intramuscular injection of triptorelin pamoate 11.25 mg at baseline and 3 months after baseline. Hormonal changes as well as safety and efficacy endpoints were measured at baseline, 3 months, and 6 months. The baseline characteristics of the 37 patients in the TP Study were similar to those of the TA Study population. A suppressed luteinising hormone (LH) response (LH peak ≤3 IU/l) to the gonadotrophin-releasing hormone test at 3 months (primary endpoint) occurred in 83.8 and 82.8% of the cases in the TP and the TA Study, respectively. At 6 months, a suppressed LH response occurred in 86.5 and 96.8% of the cases in the TP and the TA Study, respectively. Pubertal development was slowed in both studies. Adverse events were mild to moderate and resolved without sequelae in the TP Study. Triptorelin pamoate 11.25 mg administered at 3-month intervals is an effective and well-tolerated treatment in patients with CPP. The efficacy and safety profiles appear similar to those reported in the literature for triptorelin acetate 11.25 mg. © 2016 S. Karger AG, Basel.

Genetics Home Reference: familial male-limited precocious puberty

MedlinePlus

... male-limited precocious puberty Familial male-limited precocious puberty Printable PDF Open All Close All Enable Javascript ... expand/collapse boxes. Description Familial male-limited precocious puberty is a condition that causes early sexual development ...

Nocturnal Urinary Excretion of FSH and LH in Children and Adolescents With Normal and Early Puberty.

PubMed

Kolby, Nanna; Busch, Alexander S; Aksglaede, Lise; Sørensen, Kaspar; Petersen, Jorgen Holm; Andersson, Anna-Maria; Juul, Anders

2017-10-01

Clinical use of single serum gonadotropin measurements in children is limited by the pulsatile secretion of follicle-stimulating hormone (FSH) and luteinizing hormone (LH). However, first morning voided (FMV) urine may integrate the fluctuating gonadotropin serum levels. We aimed to evaluate urinary and serum gonadotropin levels according to age, sex, and pubertal stage in healthy children and to assess the clinical use of FMV urinary gonadotropins in children with disordered puberty. Cross-sectional part of the COPENHAGEN Puberty Study and longitudinal study of patients. Population-based and outpatient clinic. Eight hundred forty-three healthy children from the COPENHAGEN Puberty Study and 25 girls evaluated for central precocious puberty (CPP). Clinical pubertal staging, including serum and urinary gonadotropin levels. Urinary gonadotropins increased with advancing age and pubertal development and were detectable in FMV urine before physical signs of puberty. FMV urinary LH correlated strongly with basal (r = 0.871, P < 0.001) and gonadotropin-releasing hormone (GnRH)-stimulated serum LH (r = 0.82, P < 0.001). Urinary LH was superior to urinary FSH in differentiating the pubertal stage. Receiver operating curve analysis revealed that a cut-off standard deviation (SD) score of 2 for urinary LH (IU/L) gave a sensitivity of 75% and a specificity of 92% in predicting a positive GnRH stimulation test (LHmax > 5 IU/L). Urinary concentrations of LH decreased after 3 months of GnRH treatment to levels below +2 SDs. Urinary gonadotropin levels increased before the onset of puberty and were elevated in girls with CPP. We suggest urinary LH as an alternative noninvasive method to improve diagnosing and therapeutic management of children with disordered puberty. Copyright © 2017 Endocrine Society

True Precocious Puberty Following Treatment of a Leydig Cell Tumor: Two Case Reports and Literature Review.

PubMed

Verrotti, Alberto; Penta, Laura; Zenzeri, Letizia; Lucchetti, Laura; Giovenali, Paolo; De Feo, Pierpaolo

2015-01-01

Leydig cell testicular tumors are a rare cause of precocious pseudopuberty in boys. Surgery is the main therapy and shows good overall prognosis. The physical signs of precocious puberty are expected to disappear shortly after surgical removal of the mass. We report two children, 7.5 and 7.7 year-old boys, who underwent testis-sparing surgery for a Leydig cell testicular tumor causing precocious pseudopuberty. During follow-up, after an immediate clinical and laboratory regression, both boys presented signs of precocious puberty and ultimately developed central precocious puberty. They were successfully treated with gonadotropin-releasing hormone (GnRH) analogs. Only six other cases have been described regarding the development of central precocious puberty after successful treatment of a Leydig cell tumor causing precocious pseudopuberty. Gonadotropin-dependent precocious puberty should be considered in children treated for a Leydig cell tumor presenting persistent or recurrent physical signs of puberty activation. In such cases, therapy with GnRH analogs appears to be the most effective medical treatment.

Disorders of childhood growth and development: precocious puberty.

PubMed

Chauhan, Alia; Grissom, Maureen

2013-07-01

Precocious puberty is defined as pubertal development that begins at an earlier age than expected; most US pediatric endocrinology subspecialists use cutoff ages of 8 years for girls and 9 years for boys. Early activation and maturation of the hypothalamic-pituitary-gonadal axis leads to hormonal changes, physical signs of puberty, and acceleration of linear growth. Factors affecting puberty include race/ethnicity, obesity, and endocrine disruptors. The 2 forms of precocious puberty are central (gonadotropin-dependent precocious puberty) and peripheral (gonadotropin-independent precocious puberty). Most cases of the former have no identifiable etiology, whereas the latter is caused by increased secretion of sex hormones by the gonads or adrenal glands. It is important to differentiate progressive from nonprogressive precocious puberty to avoid unnecessary treatment for the latter; if diagnosis is uncertain, the child should be reassessed within several months. Evaluation begins with a detailed history and physical examination followed by an x-ray for bone age; in precocious puberty, bone age is greater than chronologic age. If indicated, additional serum testing (basal luteinizing hormone) and imaging studies should be obtained. Patients should be referred to a pediatric endocrinology subspecialist for treatment. It is essential to manage underlying etiologies. Gonadotropin-releasing hormone agonists should be considered only for children with progressive central precocious puberty to prevent short stature. For children with apparent nonprogressive precocious puberty, follow-up every 3 to 6 months between ages 6 and 7 years is recommended to assess for progression. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

Meta-Analysis of Paediatric Patients with Central Precocious Puberty Treated with Intramuscular Triptorelin 11.25 mg 3-Month Prolonged-Release Formulation
.

PubMed

Durand, Adélaïde; Tauber, Maithé; Patel, Bharat; Dutailly, Pascale

2017-01-01

A meta-analysis was undertaken to assess the effect of triptorelin 11.25 mg 3-month prolonged-release formulation in central precocious puberty (CPP). All available clinical studies with triptorelin 11.25 mg were included. The primary outcome was the proportion of children with suppressed luteinising hormone (LH) response (peak LH ≤3 IU/L) to the gonadotrophin-releasing hormone (GnRH) test 3 months after triptorelin 11.25 mg injection. Secondary outcomes included: the proportion with suppressed peak LH response at 6 months and the proportion with suppressed peak follicle-stimulating hormone (FSH) response (≤3 IU/L), suppressed oestradiol (≤20 pmol/L) in girls or suppressed testosterone (≤30 ng/dL) in boys at 3 months. 153 children (13 boys, 140 girls) were included. The proportion with a suppressed peak LH response to the GnRH test was 87.6% (95% CI: 81.3-92.4, p < 0.0001, for a proportion >70%) and 92.8% (95% CI: 87.5-96.4, p < 0.0001, for a proportion >70%) at 3 and 6 months, respectively. FSH peak, oestradiol, and testosterone were suppressed in 86.7% (95% CI: 79.1-92.4), 97.1% (95% CI: 91.6-99.4), and 72.7% (95% CI: 39.0-94.0) of children at 3 months, respectively. Triptorelin 11.25 mg 3-month formulation is efficacious in suppressing LH peak and other gonadal hormones and in slowing the progression of CPP in children.
. © 2017 S. Karger AG, Basel.

Familial central precocious puberty suggests autosomal dominant inheritance.

PubMed

de Vries, Liat; Kauschansky, Arieh; Shohat, Mordechai; Phillip, Moshe

2004-04-01

The prevalence of precocious puberty is higher in certain ethnic groups, and some cases may be familial. The aim of this study was to investigate the mode of inheritance of familial precocious puberty and to identify characteristics that distinguish familial from isolated precocious puberty. Of the 453 children referred to our center for suspected precocious puberty between January 1, 1997, and December 31, 2000, 156 (147 girls and 9 boys) were found to have idiopathic central precocious puberty, which was familial in 43 (42 girls and 1 boy) (27.5%). Data of the familial and sporadic cases were compared. The familial group was characterized by a significantly lower maternal age at menarche than the sporadic group (mean, 11.47 +/- 1.96 vs. 12.66 +/- 1.18 yr; P = 0.0001) and more advanced puberty at admission (Tanner stage 2, 56.5% vs. 78.1%; P = 0.006). Segregation analysis was used to study the mode of inheritance. The segregation ratio for precocious puberty was 0.38 (0.45 after exclusion of young siblings) assuming incomplete penetrance and 0.58 (0.65 after exclusion of young siblings) assuming complete ascertainment. These results suggest autosomal dominant transmission with incomplete, sex-dependent penetrance.

Predictors of bone maturation, growth rate and adult height in children with central precocious puberty treated with depot leuprolide acetate.

PubMed

Klein, Karen O; Dragnic, Sanja; Soliman, Ahmed M; Bacher, Peter

2018-05-11

Children with central precocious puberty (CPP) are treated with gonadotropin-releasing hormone agonists (GnRHa) to suppress puberty. Optimizing treatment outcomes continues to be studied. The relationships between growth, rate of bone maturation (bone age/chronological age [ΔBA/ΔCA]), luteinizing hormone (LH), predicted adult stature (PAS), as well as variables influencing these outcomes, were studied in children treated with depot leuprolide (LA Depot) Methods: Subjects (64 girls, seven boys) with CPP received LA Depot every 3 months for up to 42 months. Multivariate regression analyses were conducted to examine the predictors affecting ΔBA/ΔCA, PAS and growth rate. Ninety percent of subjects (18 of 20) were suppressed (LH levels <4 IU/L) at 42 months. Over 42 months, the mean growth rate declined 2 cm/year, the mean BA/CA ratio decreased 0.21 and PAS increased 8.90 cm for girls (n=64). PAS improved to mid-parental height (MPH) in 46.2% of children by 30 months of treatment. Regression analysis showed that only the Body Mass Index Standardized Score (BMI SDS) was significantly associated (β+0.378 and +0.367, p≤0.05) with growth rate. For PAS, significant correlations were with MPH (β+0.808 and +0.791, p<0.001) and ΔBA/ΔCA (β+0.808 and +0.791, p<0.001). For ΔBA/ΔCA, a significant association was found only with BA at onset of treatment (β-0.098 and -0.103, p≤0.05). Peak-stimulated or basal LH showed no significant influence on growth rate, ΔBA/ΔCA or PAS. Growth rate and bone maturation rate normalized on treatment with LA Depot. LH levels were not significantly correlated with growth rate, ΔBA/ΔCA or PAS, suggesting that suppression was adequate and variations in gonadotropin levels were below the threshold affecting outcomes.

Gonadotropin-Dependent Precocious Puberty: Neoplastic Causes and Endocrine Considerations

PubMed Central

2011-01-01

Premature activation of the hypothalamic-pituitary-gonadal (HPG) axis manifests as gonadotropin-dependent precocious puberty. The mechanisms behind HPG activation are complex and a clear etiology for early activation is often not elucidated. Though collectively uncommon, the neoplastic and developmental causes of gonadotropin-dependent precocious puberty are very important to consider, as a delay in diagnosis may lead to adverse patient outcomes. The intent of the current paper is to review the neoplastic and developmental causes of gonadotropin-dependent precocious puberty. We discuss the common CNS lesions and human chorionic gonadotropin-secreting tumors that cause sexual precocity, review the relationship between therapeutic radiation and gonadotropin-dependent precocious puberty, and finally, provide an overview of the therapies available for height preservation in this unique patient population. PMID:21603196

What Are the Symptoms of Puberty, Precocious Puberty, and Delayed Puberty?

MedlinePlus

... puberty include: Growth of pubic and other body hair Growth spurt Breast development Onset of menstruation (after puberty ... of pubic hair, other body hair, and facial hair Enlargement of testicles and penis Muscle growth Growth spurt Acne Deepening of the voice Precocious ...

A new pathway in the control of the initiation of puberty: the MKRN3 gene.

PubMed

Abreu, Ana Paula; Macedo, Delanie B; Brito, Vinicius N; Kaiser, Ursula B; Latronico, Ana Claudia

2015-06-01

Pubertal timing is influenced by complex interactions among genetic, nutritional, environmental, and socioeconomic factors. The role of MKRN3, an imprinted gene located in the Prader-Willi syndrome critical region (chromosome 15q11-13), in pubertal initiation was first described in 2013 after the identification of deleterious MKRN3 mutations in five families with central precocious puberty (CPP) using whole-exome sequencing analysis. Since then, additional loss-of-function mutations of MKRN3 have been associated with the inherited premature sexual development phenotype in girls and boys from different ethnic groups. In all of these families, segregation analysis clearly demonstrated autosomal dominant inheritance with complete penetrance, but with exclusive paternal transmission, consistent with the monoallelic expression of MKRN3 (a maternally imprinted gene). Interestingly, the hypothalamic Mkrn3 mRNA expression pattern in mice correlated with a putative inhibitory input on puberty initiation. Indeed, the initiation of puberty depends on a decrease in factors that inhibit the release of GnRH combined with an increase in stimulatory factors. These recent human and animal findings suggest that MKRN3 plays an inhibitory role in the reproductive axis to represent a new pathway in pubertal regulation. © 2015 Society for Endocrinology.

Association of estrogen receptor gene polymorphisms with human precocious puberty: a systematic review and meta-analysis.

PubMed

Luo, Yan; Liu, Qin; Lei, Xun; Wen, Yi; Yang, Ya-Lan; Zhang, Rui; Hu, Meng-Yao

2015-07-01

This study aims to estimate the association between ESR1 polymorphisms (PvuII and XbaI) and ESR2 polymorphisms (RsaI and AluI) with precocious puberty. Relevant studies published before March 2014 were retrieved by a electronic search among nine databases. Meta-analysis of the pooled odds ratios (ORs) with 95% confidence intervals (CIs) was calculated. Four eligible case-control studies including 491 precocious puberty patients and 370 healthy controls were identified. Three studies reported ESR1 PvuII and XbaI polymorphism and one study reported ESR2 RsaI and AluI polymorphism. Increment of precocious puberty risk was associated with PvuII polymorphism in the heterosis model ((CT) versus TT: OR 1.42, 95% CI: 1.05-1.91, p = 0.02). Risk of precocious puberty was associated with XbaI polymorphism in the dominant model (GG + GA versus AA: OR 1.48, 95% CI: 1.11-1.97, p = 0.007) and the heterosis model (GA versus AA: OR 1.68, 95% CI: 1.23-2.29, p = 0.001). This meta-analysis suggests that ESR1 XbaI and PvuII polymorphisms are associated with precocious puberty susceptibility, and the relationship between ESR2 RsaI and AluI polymorphism with precocious puberty remains to be further investigated. Well-designed studies with large sample size among different polymorphisms and ethnicities are in urgent need to provide and update reliable data for comprehensive and definite conclusion.

Genetics Home Reference: central precocious puberty

MedlinePlus

... girls and between ages 9 and 14 in boys, girls with central precocious puberty begin exhibiting signs before ... of puberty is even earlier than normal in girls than in boys. Boys with an MKRN3 gene mutation inherited from ...

Puberty without gonadotropins. A unique mechanism of sexual development.

PubMed

Wierman, M E; Beardsworth, D E; Mansfield, M J; Badger, T M; Crawford, J D; Crigler, J F; Bode, H H; Loughlin, J S; Kushner, D C; Scully, R E

1985-01-10

Recent evidence suggests that a group of children exists in whom premature sexual maturation occurs in the absence of pubertal levels of gonadotropins; that is, they have gonadotropin-independent precocious puberty. We compared six boys and one girl with this disorder with four boys and five girls with central precocious puberty, in which there is a pubertal pattern of gonadotropin release. The two groups were similar in age of onset, degree of sexual development, growth velocity, and rate of skeletal maturation. A family history of precocity was noted in four of the boys with gonadotropin-independent precocity, and the girl had McCune-Albright syndrome. Children with central precocious puberty demonstrated a pulsatile release of gonadotropins, pubertal responses to luteinizing hormone-releasing hormone, and complete suppression of gonadarche after exposure to an analogue of luteinizing hormone-releasing hormone (LHRHa). In contrast, children with gonadotropin-independent precocity demonstrated an absence of gonadotropin pulsations, variable responses to luteinizing hormone-releasing hormone, lack of suppression of puberty in response to LHRHa, and cyclic steroidogenesis. Tissue from testicular biopsies performed in five of six boys with gonadotropin-independent precocity showed a range from incipient pubertal development of the tubules with proliferation of Leydig cells to the appearance of normal adult testes. We conclude that gonadotropin-independent precocious puberty is a distinct syndrome, of unknown cause, that may be familial and may have been responsible for many previously reported cases of precocious puberty.

Diagnosis and constitutional and laboratory features of Korean girls referred for precocious puberty

PubMed Central

Kim, Doosoo; Cho, Sung-Yoon; Maeng, Se-Hyun; Yi, Eun Sang; Jung, Yu Jin; Park, Sung Won; Sohn, Young Bae

2012-01-01

Purpose Precocious puberty is defined as breast development before the age of 8 years in girls. The present study aimed to reveal the diagnosis of Korean girls referred for precocious puberty and to compare the constitutional and endocrinological features among diagnosis groups. Methods The present study used a retrospective chart review of 988 Korean girls who had visited a pediatric endocrinology clinic from 2006 to 2010 for the evaluation of precocious puberty. Study groups comprised fast puberty, true precocious puberty (PP), pseudo PP, premature thelarche, and control. We determined the height standard deviation score (HSDS), weight standard deviation score (WSDS), and body mass index standard deviation score (BMISDS) of each group using the published 2007 Korean growth charts. Hormone tests were performed at our outpatient clinic. Results The PP groups comprised fast puberty (67%), premature thelarche (17%), true PP (15%), and pseudo PP (1%). Advanced bone age and levels of estradiol, basal luteinizing hormone (LH), and peak LH after gonadotropin-releasing hormone stimulation testing were significantly high in the fast puberty and true PP groups compared with the control group. HSDS, WSDS, and BMISDS were significantly higher in the true PP group than in the control group (P<0.05). Conclusion The frequent causes of PP were found to be fast puberty, true PP, and premature thelarche. Furthermore, BMISDS were significantly elevated in the true PP group. Therefore, we emphasize the need for regular follow-up of girls who are heavier or taller than others in the same age group. PMID:23300504

Precocious puberty

MedlinePlus

... period (menstruation) Mature outer genitals In boys, precocious puberty is when any of the following develop before age 9: Armpit or pubic hair Growth of the testes and penis Facial hair, often first on the upper lip ...

Complete androgen insensitivity syndrome associated with male gender identity or female precocious puberty in the same family.

PubMed

Bermúdez de la Vega, José A; Fernández-Cancio, Mónica; Bernal, Susana; Audí, Laura

2015-01-01

In 4 complete androgen insensitivity syndrome (CAIS) members of one family, 2 presented extreme and unusual clinical features: male gender identity disorder (case 1) and female precocious central puberty (case 2). The AR gene carried the mutation c.1752C>G, p.Phe584Leu. Gender dysphoria in CAIS may be considered as a true transgender and has been described in 3 other cases. Central precocious puberty has only been described in 1 case; Müllerian ducts in case 2 permitted menarche. Despite the common CAIS phenotype, there was a familial disparity for gender identity adequacy and timing and type of puberty.

[Precocious puberty and von Recklinghausen's disease].

PubMed

Barg, Ewa; Wikiera, Beata; Basiak, Aleksander; Głab, Ewa

2006-01-01

Von Recklinghausen's disease belongs to a group of neurocutaneous syndromes and is characterised by skin, nerve and bone abnormalities. We present a case of von Recklinghausen's disease and precocious puberty in 7-year-old boy. At the age of three café au lait spots on the skin and an incranial tumour situated near the optic chiasm--qualified as inoperable--were discovered. At the age of 7 first signs of precocious puberty appeared (pubic hair P3 and enlargement of the testes (15 ml) and penis). Laboratory measurements included: LH 7.5 mIU/ml, FSH 1.1 mIU/ml, testosterone 183 ng/ml, assessment of bone age: 9 years. The response to LHRH stimulation was characteristic for true precocious puberty (LH 15.9 mIU/ml and FSH 1.5 mIU/ml after 30 minutes). The MRI of the brain showed a tumour of the suprasellar region with compression of pituitary stalk. True precocious puberty was diagnosed. Treatment with Diphereline was introduced. At present the boy is 9 years old and has been treated with Diphereline for 16 months. The volume of the testicles has decreased to 7 ml and loss of pubic hair was noted. The MRI does not show any progression in tumour growth. The authors would like to underline the need of close observation of children with von Reclinghausen disease with regard to possibility of uncovering true precocious puberty which is critical for rapid diagnosis and introduction of correct treatment.

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

PubMed

Hammadur Rahaman, S K; Khandelwal, Deepak; Khadgawat, Rajesh; Kandasamy, Devasenathipathy; Bakhshi, Sameer

2018-03-15

Pineal gland lesions usually present with central precocious puberty. A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. He received chemotherapy followed by radiotherapy and responded well. CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

Precocious Puberty (For Parents)

MedlinePlus

... stimulate the ovaries (in girls) or testicles (in boys) to make sex hormones. Sometimes, precocious puberty stems from a structural ... or pubic or underarm hair. The physical changes boys and girls go through ... to look for high levels of sex hormones. And X-rays of your child's wrist ...

Mutational Analysis of TAC3 and TACR3 Genes in Patients with Idiopathic Central Pubertal Disorders

PubMed Central

Tusset, Cintia; Noel, Sekoni D.; Trarbach, Ericka B.; Silveira, Letícia F. G.; Jorge, Alexander A. L.; Brito, Vinicius N.; Cukier, Priscila; Seminara, Stephanie B.; de Mendonça, Berenice B.; Kaiser, Ursula B.; Latronico, Ana Claudia

2013-01-01

Aim To investigate the presence of variants in the TAC3 and TACR3 genes, which encode NKB and its receptor (NK3R), respectively, in a large cohort of patients with idiopathic central pubertal disorders. Patients and Methods Two hundred and thirty seven patients were studied: 114 with central precocious puberty (CPP), 73 with normosmic isolated hypogonadotropic hypogonadism (IHH) and 50 with constitutional delay of growth and puberty (CDGP). The control group consisted of 150 Brazilian individuals with normal pubertal development. Genomic DNA was extracted from peripheral blood and the entire coding region of both TAC3 and TACR3 genes were amplified and automatically sequenced. Results We identified one variant (p.A63P) in NKB and four variants, p.G18D, p.L58L (c.172C>T), p.W275* and p.A449S in NK3R, which were absent in the control group. The p.A63P variant was identified in a girl with CPP, and p.A449S in a girl with CDGP. The known p.G18D, p.L58L and p.W275* variants were identified in three unrelated males with normosmic IHH. Conclusion Rare variants in the TAC3 and TACR3 genes were identified in patients with central pubertal disorders. Loss-of-function variants of TACR3 were associated with the normosmic IHH phenotype. PMID:23329188

High Prevalence of Precocious Puberty and Obesity in Childhood Narcolepsy with Cataplexy

PubMed Central

Poli, Francesca; Pizza, Fabio; Mignot, Emmanuel; Ferri, Raffaele; Pagotto, Uberto; Taheri, Shahrad; Finotti, Elena; Bernardi, Filippo; Pirazzoli, Piero; Cicognani, Alessandro; Balsamo, Antonio; Nobili, Lino; Bruni, Oliviero; Plazzi, Giuseppe

2013-01-01

Study Objectives: We analyzed the potential predictive factors for precocious puberty, observed in some cases of childhood narcolepsy with cataplexy (NC) and for obesity, a much more common feature of NC, through a systematic assessment of pubertal staging, body mass index (BMI), and metabolic/endocrine biochemical analyses. Design: Cross-sectional on consecutive recruitment. Setting: Hospital sleep center and pediatric unit. Patients: Forty-three children and adolescents with NC versus 52 age-matched obese children as controls. Interventions: N/A. Measurements and Results: Patients underwent clinical interview, polysomnographic recordings, cerebrospinal fluid hypocretin-1 measurement, and human leukocyte antigen typing. Height, weight, arterial blood pressure, and Tanner pubertal stage were evaluated. Plasma lipid and glucose profiles were analyzed. When an altered pubertal development was clinically suspected, plasma concentrations of hypothalamic-pituitary-gonadal axis hormones were determined. Children with NC showed a high prevalence of overweight/obesity (74%) and a higher occurrence of precocious puberty (17%) than obese controls (1.9%). Isolated signs of accelerated pubertal development (thelarche, pubic hair, advanced bone age) were also present (41%). Precocious puberty was significantly predicted by a younger age at first NC symptom onset but not by overweight/obesity or other factors. In addition, overweight/obesity was predicted by younger age at diagnosis; additional predictors were found for overweight/obesity (short disease duration, younger age at weight gain and lower high-density lipoprotein cholesterol), which did not include precocious puberty. NC symptoms, pubertal signs appearance, and body weight gain developed in close temporal sequence. Conclusions: NC occurring during prepubertal age is frequently accompanied by precocious puberty and overweight/obesity, suggesting an extended hypothalamic dysfunction. The severity of these comorbidities and the potential related risks require a multidiagnostic approach and a tailored therapeutic management. Citation: Poli F; Pizza F; Mignot E; Ferri R; Pagotto U; Taheri S; Finotti E; Bernardi F; Pirazzoli P; Cicognani A; Balsamo A; Nobili L; Bruni O; Plazzi G. High prevalence of precocious puberty and obesity in childhood narcolepsy with cataplexy. SLEEP 2013;36(2):175–181. PMID:23372264

Experience with cyproterone acetate in the treatment of precocious puberty.

PubMed

Laron, Z; Kauli, R

2000-07-01

The authors review their experience (1967-present) in the use of cyproterone acetate (CPA) in precocious puberty. CPA was found effective in persistently suppressing pituitary gonadotropic secretion when administered orally at a dose of 50 mg b.i.d. (70-100 mg/d). After the introduction of gonadotropic analogues (GnRHa) for treatment of central precocious puberty, short term use of CPA was found useful to counteract the initial stimulatory effect of the GnRHa as well as an adjunct drug in case of very active adrenarche causing advanced bone age during GnRHa treatment. The final heights of girls treated with CPA and girls treated with D-Trp6-LHRH were found comparable: 157.8+/-5.1 cm vs 159.6+/-6.3 cm, respectively. The main adverse effects were occasional fatigue due to partial adrenal insufficiency with CPA and gynecomastia in a few boys. Liver function tests were normal in all patients with the exception of one boy with severe hypothalamic disease, including precocious puberty, who developed liver cirrhosis 3 years after stopping CPA following 5 years treatment. Other indications for CPA treatment during childhood and adolescence, such as fast puberty, congenital adrenal hyperplasia and acne, are also mentioned.

A single sample GnRHa stimulation test in the diagnosis of precocious puberty

USDA-ARS?s Scientific Manuscript database

Gonadotropin-releasing hormone (GnRH) has been the standard test for diagnosing central precocious puberty. Because GnRH is no longer available, GnRH analogues (GnRHa) are now used. Random LH concentration, measured by the third-generation immunochemiluminometric assay, is a useful screening tool ...

Qualitative assessment of precocious puberty-related user-created contents on YouTube.

PubMed

Nam, Hyo-Kyoung; Bang, Soo Min; Rhie, Young Jun; Park, Sang Hee; Lee, Kee-Hyoung

2015-09-01

User-created content (UCC) has provided a considerable amount of medical information and become an important source. We aimed to evaluate the quality and scientific accuracy of precocious puberty-related UCC on YouTube. The keywords "precocious puberty", "early puberty", "sexual precocity", and "precocity" were searched for on YouTube during June and July 2014. More than 1,500 UCC matched the keywords. According to the information provider, UCC was classified as medical, oriental, or commercial & others. We evaluated the quality and scientific accuracy of the information provided in UCC using the DISCERN instrument and information scores, respectively. We selected 51 UCC, which were categorized into three types: medical (n=17), oriental (n=17), or commercial & others (n=17). The overall quality score for medical UCC (3.4) was significantly higher relative to those of oriental and commercial & others UCC (2.8 and 2.3, respectively) (P<0.001). In the assessment of scientific accuracy, the mean information score for medical UCC (30.7) was significantly higher than those of oriental and commercial & others UCC (15.9 and 5.1, respectively) (P<0.001). The mean duration of oriental UCC was the longest (P<0.001), however, it was viewed less frequently among them (P=0.086). The quality and accuracy of precocious puberty-related health information in UCC were variable and often unreliable. The overall quality of UCC regarding precocious puberty was moderate. Only medical UCC provided scientifically accurate information. As UCC becomes a popular source of health information, it is important to provide reliable, scientifically accurate information.

Qualitative assessment of precocious puberty-related user-created contents on YouTube

PubMed Central

Nam, Hyo-Kyoung; Bang, Soo Min; Rhie, Young Jun; Park, Sang Hee

2015-01-01

Purpose User-created content (UCC) has provided a considerable amount of medical information and become an important source. We aimed to evaluate the quality and scientific accuracy of precocious puberty-related UCC on YouTube. Methods The keywords "precocious puberty", "early puberty", "sexual precocity", and "precocity" were searched for on YouTube during June and July 2014. More than 1,500 UCC matched the keywords. According to the information provider, UCC was classified as medical, oriental, or commercial & others. We evaluated the quality and scientific accuracy of the information provided in UCC using the DISCERN instrument and information scores, respectively. Results We selected 51 UCC, which were categorized into three types: medical (n=17), oriental (n=17), or commercial & others (n=17). The overall quality score for medical UCC (3.4) was significantly higher relative to those of oriental and commercial & others UCC (2.8 and 2.3, respectively) (P<0.001). In the assessment of scientific accuracy, the mean information score for medical UCC (30.7) was significantly higher than those of oriental and commercial & others UCC (15.9 and 5.1, respectively) (P<0.001). The mean duration of oriental UCC was the longest (P<0.001), however, it was viewed less frequently among them (P=0.086). Conclusion The quality and accuracy of precocious puberty-related health information in UCC were variable and often unreliable. The overall quality of UCC regarding precocious puberty was moderate. Only medical UCC provided scientifically accurate information. As UCC becomes a popular source of health information, it is important to provide reliable, scientifically accurate information. PMID:26512350

Child Development & Behavior Topics

MedlinePlus

... Willi Syndrome (PWS) Precocious Puberty Pregnancy and Smoking Pregnancy Prevention Resources for Teens and Families Preventing Tobacco Use Prom! Keeping it Safe and Fun— Resources for Teens and Their Parents Pseudohermaphroditism Puberty, Early Puberty, Early, Podcast Puberty, Late, Podcast Back to ...

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism

PubMed Central

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Learning points: Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty. Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH. Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function. PMID:28721217

An FSH and TSH pituitary adenoma, presenting with precocious puberty and central hyperthyroidism.

PubMed

Vargas, Guadalupe; Balcazar-Hernandez, Lourdes-Josefina; Melgar, Virgilio; Magriña-Mercado, Roser-Montserrat; Gonzalez, Baldomero; Baquera, Javier; Mercado, Moisés

2017-01-01

A 19-year-old woman with a history of isosexual precocious puberty and bilateral oophorectomy at age 10 years because of giant ovarian cysts, presents with headaches and mild symptoms and signs of hyperthyroidism. Hormonal evaluation revealed elevated FSH and LH levels in the postmenopausal range and free hyperthyroxinemia with an inappropriately normal TSH. Pituitary MRI showed a 2-cm macroadenoma with suprasellar extension. She underwent successful surgical resection of the pituitary tumor, which proved to be composed of two distinct populations of cells, each of them strongly immunoreactive for FSH and TSH, respectively. This mixed adenoma resulted in two different hormonal hypersecretion syndromes: the first one during childhood and consisting of central precocious puberty and ovarian hyperstimulation due to the excessive secretion of biologically active FSH and which was not investigated in detail and 10 years later, central hyperthyroidism due to inappropriate secretion of biologically active TSH. Although infrequent, two cases of isosexual central precocious puberty in girls due to biologically active FSH secreted by a pituitary adenoma have been previously reported in the literature. However, this is the first reported case of a mixed adenoma capable of secreting both, biologically active FSH and TSH. Although functioning gonadotrophinomas are infrequent, they should be included in the differential diagnosis of isosexual central precocious puberty.Some functioning gonadotrophinomas are mixed adenomas, secreting other biologically active hormones besides FSH, such as TSH.Early recognition and appropriate treatment of these tumors by transsphenoidal surgery is crucial in order to avoid unnecessary therapeutic interventions that may irreversibly compromise gonadal function.

Adrenocorticotropin-dependent precocious puberty of testicular origin in a boy with X-linked adrenal hypoplasia congenita due to a novel mutation in the DAX1 gene.

PubMed

Domenice, S; Latronico, A C; Brito, V N; Arnhold, I J; Kok, F; Mendonca, B B

2001-09-01

Primary adrenal insufficiency is a rare condition in pediatric age, and its association with precocious sexual development is very uncommon. We report a 2-yr-old Brazilian boy with DAX1 gene mutation whose first clinical manifestation was isosexual gonadotropin-independent precocious puberty. He presented with pubic hair, enlarged penis and testes, and advanced bone age. T levels were elevated, whereas basal and GnRH-stimulated LH levels were compatible with a prepubertal pattern. Chronic GnRH agonist therapy did not reduce T levels, supporting the diagnosis of gonadotropin-independent precocious puberty. Testotoxicosis was ruled out after normal sequencing of exon 11 of the LH receptor gene. At age 3 yr he developed clinical and hormonal features of severe primary adrenal insufficiency. The entire coding region of the DAX1 gene was analyzed through direct sequencing. A nucleotide G insertion between nucleotides 430 and 431 in exon 1, resulting in a novel frameshift mutation and a premature stop codon at position 71 of DAX-1, was identified. Surprisingly, steroid replacement therapy induced a clear decrease in testicular size and T levels to the prepubertal range. These findings suggest that chronic excessive ACTH levels resulting from adrenal insufficiency may stimulate Leydig cells and lead to gonadotropin-independent precocious puberty in some boys with DAX1 gene mutations.

A Case of Atypical McCune-Albright Syndrome with Vaginal Bleeding

PubMed Central

Rostampour, Noushin; Hashemipour, Mahin; Kelishadi, Roya; Hovsepian, Silva; Hekmatnia, Ali

2011-01-01

Background McCune-Albright syndrome (MAS) is a rare non-inherited disorder characterized by the clinical triad of precocious puberty, cafe-au-lait skin lesions, and fibrous dysplasia of bone. Case Presentation We report a girl with MAS, presenting initially with vaginal bleeding at the age of 17 months. Ultrasonography revealed unilateral ovarian cysts and ureteral and ovarian enlargement. Considering the clinical and paraclinical findings, the patient diagnosed as a case of gonadotropin-independent precocious puberty was treated with medroxy-progestrone acetate (MPA) for three months. During the follow up, recurrent episodes of bleeding, ovarian activation and cyst formation, as well as breast size development were reported. At the age of 5.5 years, fibrous dysplasia was detected, which in coexistence with precocious puberty confirmed the diagnosis of MAS. The patient had no cafe-au-lait skin macles during follow up. Conclusion Considering that clinical manifestations of MAS appear later in the course of recurrent periods of ovarian activation and cyst formation, a careful clinical observation and follow up of patients is necessary and the diagnosis of MAS must be kept in mind in cases with gonadotropin-independent precocious puberty. PMID:23056821

GnRH-dependent precocious puberty manifested at the age of 14 months in a girl with 47,XXX karyotype.

PubMed

Skordis, Nicos; Ferrari, Eleana; Antoniadou, Aria; Phylactou, Leonidas A; Fanis, Pavlos; Neocleous, Vassos

2017-07-01

This case report describes a 47,XXX girl who presented very early, at the age of 14 months, with signs of sexual precocity (breast and pubic hair development, menarche) and was finally diagnosed with GnRH dependent precocious puberty with no evidence of underlying central nervous system pathology. Molecular testing did not identify any genetic defect in any of the genes tested (KISS1, KISS1R, DLK1 and the intronless MKRN3). Though previous studies have shown a link between karyotype 47,XXX and precocious puberty, this is the youngest patient reported so far. Treatment with GnRH analog was commenced and proved to be effective, indicating a successful suppression of the hypothalamic-pituitary-ovarian axis.

Investigating the relationship between precocious puberty and obesity: a cross-sectional study in Shanghai, China

PubMed Central

Chen, Chang; Zhang, Yunting; Sun, Wanqi; Chen, Yao; Jiang, Yanrui; Song, Yuanjin; Lin, Qinmin; Zhu, Lixia; Zhu, Qi; Wang, Xiumin; Jiang, Fan

2017-01-01

Objectives Obesity is reported to be closely relevant to early sexual development but the relationship between sexual precocity and obesity or central obesity is still inconsistent, especially in boys. We aimed to investigate the relationship between precocious puberty and obesity as well as central obesity. Design A large population-based cross-sectional study using multistage, stratified cluster random sampling. Setting Data from the Shanghai Children’s Health, Education and Lifestyle Evaluation (SCHEDULE) study in June 2014. Participants 17 620 Chinese children aged 6–12 years. Primary and secondary outcome measures Obesity was defined by WHO Child Growth Standards. Central obesity was defined by sex-specific waist-to-height ratio (WHtR) cut-offs (WHtR ≥0.48 for boys, WHtR ≥0.46 for girls). Precocious puberty was identified by Tanner stage of breast, pubic hair and testicle development. A χ2 test was performed to compare rates. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the association between precocious puberty and general obesity and central obesity. Probit analysis was used for estimating the median age at entry into Tanner stage 2 or greater for breast, pubic hair and testicle development. Linear regression was utilised to compare the effects of WHtR and body mass index (BMI) on sex development indicators. Results 25.98% and 38.58% of boys with precocious puberty were respectively accompanied by obesity (OR=2.15, 95% CI=1.31 to 3.50) or central obesity (OR=2.10, 95% CI=1.46 to 3.03); meanwhile, 13.86% and 29.42% of girls with precocious puberty were respectively accompanied by obesity (OR=9.00, 95% CI=5.60 to 14.46) or central obesity (OR=5.40, 95% CI=4.10 to 7.12). The median ages of breast, pubic hair and testicle development decreased with BMI increase and median ages of thelarche and testicular development rather than pubarche were earlier in children with central obesity. Conclusions Earlier pubertal development was positively associated with obesity and central obesity in Chinese children. PMID:28400459

[Psychopathology related to women pubertal precocity].

PubMed

Purper-Ouakil, D; Didillon, A

2016-10-01

Puberty is a developmental process characterized by hormonal and physical changes leading to the ability of reproduction. Precocious puberty, especially in girls, has been associated with an increased incidence of emotional and behavioral problems. Adolescence is a life stage influenced both by the biological changes of puberty and the emergence of new social challenges. In individuals facing these developmental issues at a younger age than expected, the exposure to internal and external stress factors may be greater than in other young people. This narrative review provides an overview of psychopathology associated with precocious puberty in order to raise awareness of clinicians dealing with adolescents at risk for adverse behavioral and emotional outcomes. Developmental challenges of standard puberty and adolescence will be outlined before a more detailed description of recent findings from clinical and epidemiological studies. Putative mechanisms underlying the association between precocious puberty and psychopathology will also be discussed. Epidemiological studies have shown that an early onset of puberty in girls is associated with an earlier onset of sexuality, an earlier age of first birth and a lesser professional qualification regardless of cognitive abilities and socio-economic status. In both population studies and clinical cohorts, girls with an early age of puberty or in treatment for precocious puberty have more disruptive behavior disorders such as conduct disorders, more substance abuse disorders and delinquent behavior compared to their standard developing peers. Precocious puberty and behavioral problems may have common genetic and environmental risk factors. In young people with conduct disorders and early puberty, findings have emphasized the role of non-shared environmental factors. Low birth weight, obesity, exposure to endocrine-disrupting chemicals and adoption are potentially shared between both conditions. Early puberty in girls is also associated with psychosocial stressors and at-risk environments. The early development of secondary sexual characteristics in girls attracts older and more deviant peers, raising probability of sexual contacts but also of drug use and of a disengagement in school activities. Adolescence is the life stage during which prevalence of depressive disorders rises significantly, especially in girls. Hormonal changes and increase of the Body Mass Index leading to dissatisfaction with body image, have been put forward to explain this trend. Psychosocial challenges (emerging sexuality, instability of identity and social role) are other sources of stress at this particular period of life characterized by emotional hyper-reactivity. These stressors may have greater impact in young people showing a discrepancy between physical and affective maturation. Follow-up studies have shown that emotional and behavioral problems tend to lessen with time. Nevertheless, a heightened risk of depressive disorder remains in girls having had an early onset of puberty when other risk factors co-exist. Early puberty, especially in girls, has been associated with a number of emotional and behavioral symptoms and difficulties in adaptive functioning. Even though these adverse outcomes seem to lessen with time, heightened risk for depression and negative impact on socio-professional outcomes persist in subjects with other risk factors. The impact of treatment of precocious puberty on psycho-behavioral outcomes is currently unknown. However, clinicians should be aware that the social and emotional challenges these adolescents with atypical pubertal development have to face put them at risk for psychopathology and are potentially accessible to preventive actions. Copyright © 2016 L'Encéphale, Paris. Published by Elsevier Masson SAS. All rights reserved.

Novel C617Y mutation in the 7th transmembrane segment of luteinizing hormone/choriogonadotropin receptor in a Japanese boy with peripheral precocious puberty.

PubMed

Nagasaki, Keisuke; Katsumata, Noriyuki; Ogawa, Yohei; Kikuchi, Toru; Uchiyama, Makoto

2010-01-01

Testotoxicosis, also known as familial male-limited precocious puberty, is an autosomal dominant form of gonadotropin-independent precocious puberty caused by heterozygous constitutively activating mutations of the LHCGR gene encoding the luteinizing hormone/choriogonadotropin receptor (LH/CGR). The patient is an 8-year-old boy who started to develop pubic hair and penile enlargement at 6 years of age. The patient had elevated serum testosterone levels, but initially exhibited a prepubertal response of gonadotropins to GnRH, which was followed by central activation of the hypothalamo-pituitary-gonadal axis. The father reported having experienced precocious puberty, and is 158 cm tall. There is no history of short stature and precocious puberty in the family except for the father. The LHCGR gene was analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. The wild-type and mutant LH/CGRs were transiently expressed in COS-1 cells and cAMP levels in the cells were determined with or without hCG stimulation. Genetic analysis revealed a novel C617Y mutation of the LHCGR gene in the patient and his mother, while his father had no mutations. Functional expression study demonstrated around 15% increase in the basal intracellular cAMP level in cells expressing the mutant LH/CGR compared with that in cells expressing the wild-type receptor. We have reported the first missense C617Y mutation located in the 7th transmembrane segment of LH/CGR causing testotoxicosis. The modest phenotype of our patient may be explained, at least in part, by the modest increase in the intracellular cAMP level caused by the C617Y mutation.

[Experimental study on therapeutic effect of Dabuyin Wan on true precocious puberty in female rats].

PubMed

Cheng, Min; Ye, Xiao-Di; Miao, Yun-Ping; Chen, Ai-Ying; Zheng, Gao-Li

2013-02-01

To study the therapeutic effect of Dabuyin Wan on true precocious puberty of female rats and its possible mechanism. Twenty-two-day-old female SD rats were subcutaneously injected with 40 mg x kg(-1) N-methyl-DL-aspartic acid (NMA) at 14:00 and 16:00 every day; meanwhile, the rats were given Dabuyin Wan for intervention. Visual inspection was conducted for the time of vaginal opening. The first estrus was observed by yaginal smear test. Their ovaries and uterus were weighed to calculate organ coefficients. Conventional pathological slices were made to observe morphological changes in ovaries and uterus and calculate the thickness of uterine walls and the number of corpus luteums. The level of E2 in serum was detected to assess the therapeutic effect of Dabuyin Wan on NMA precocious puberty in rats. expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus were measured by semi-quantitative RT-PCR to investigate the possible mechanism of Dabuyin Wan. Dabuyin Wan at 3.24 g x kg(-1) and 1.62 g x kg(-1) significantly decreased the organ coefficients in rats with precocious puberty (P < 0.05), decrease the number of vaginal openings in rats (P < 0.01) and the thickness of uterine walls and the number of corpus luteums (P < 0.05), and notably down-regulated expressions of GnRH, GPR54 and Kiss-1 mRNA in hypothalamus (P < 0.05), without significant impact on E2 in serum. Dabuyin Wan may inhibit GnRH synthesis and release as well as startup of hypothalamic-pituitary-gonadal axis by down-regulating Kiss-1/GPR54 mRNA expression in hypothalamus, in order to realize the therapeutic effect on true precocious puberty.

Virilizing adrenocortical carcinoma advancing to central precocious puberty after surgery.

PubMed

Kim, Min Sun; Yang, Eu Jeen; Cho, Dong Hyu; Hwang, Pyung Han; Lee, Dae-Yeol

2015-05-01

Adrenocortical carcinoma (ACC) in pediatric and adolescent patients is rare, and it is associated with various clinical symptoms. We introduce the case of an 8-year-old boy with ACC who presented with peripheral precocious puberty at his first visit. He displayed penis enlargement with pubic hair and facial acne. His serum adrenal androgen levels were elevated, and abdominal computed tomography revealed a right suprarenal mass. After complete surgical resection, the histological diagnosis was ACC. Two months after surgical removal of the mass, he subsequently developed central precocious puberty. He was treated with a gonadotropin-releasing hormone agonist to delay further pubertal progression. In patients with functioning ACC and surgical removal, clinical follow-up and hormonal marker examination for the secondary effects of excessive hormone secretion may be a useful option at least every 2 or 3 months after surgery.

What Are Normal Puberty, Precocious Puberty, and Delayed Puberty?

MedlinePlus

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[Familial male-limited precocious puberty due to Asp578His mutations in the LHCGR gene: clinical characteristics and gene analysis in an infant].

PubMed

Wang, Min; Li, Min; Liu, Yue-Sheng; Lei, Si-Min; Xiao, Yan-Feng

2017-11-01

The aim of the study was to provide a descriptive analysis of familial male-limited precocious puberty (FMPP), which is a rare inherited disease caused by heterozygous constitutively activating mutations of the luteinizing hormone/choriogonadotropin receptor gene (LHCGR). The patient was a ten-month-old boy, presenting with penile enlargement, pubic hair formation, and spontaneous erections. Based on the clinical manifestations and laboratory data, including sexual characteristics, serum testosterone levels, GnRH stimulation test, and bone age, this boy was diagnosed with peripheral precocious puberty. Subsequently the precocious puberty-related genes were analyzed by direct DNA sequencing of amplified PCR products from the patient and his parents. Genetic analysis revealed a novel heterozygous missense mutation c.1732G>C (Asp578His) of the LHCGR gene exon11 in the patient, which had never been reported. His parents had no mutations. After combined treatment with aromatase inhibitor letrozole and anti-androgen spironolactone for six months, the patient's symptoms were controlled. The findings in this study expand the mutation spectrum of the LHCGR gene, and provide molecular evidence for the etiologic diagnosis as well as for the genetic counseling and prenatal diagnosis in the family.

Relationships between urinary biomarkers of phytoestrogens, phthalates, phenols, and pubertal stages in girls

PubMed Central

Chakraborty, Tandra R; Alicea, Eilliut; Chakraborty, Sanjoy

2012-01-01

Phytoestrogens, phthalates, and phenols are estrogen-disrupting chemicals that have a pronounced effect at puberty. They are exogenous chemicals that are either plant-derived or man-made, and can alter the functions of the endocrine system and cause various health defects by interfering with the synthesis, metabolism, binding, or cellular responses of natural estrogens. Phytoestrogens, phthalates, and phenols are some of the potent estrogens detectable in urine. Phytoestrogens are plant-derived xenestrogens found in a wide variety of food products, like soy-based food, beverages, several fruits, and vegetables. Exposure to phytoestrogens can delay breast development and further lead to precocious puberty. The effect of phytoestrogens is mediated through estrogen receptors α and β or by binding with early immediate genes, such as jun and fos. Phthalates are multifunctional synthetic chemicals used in plastics, polyvinyl chloride products, cosmetics, hair spray, and children’s toys. Phthalates have been shown to cause defeminization, thelarche, precocious puberty, and an increase in breast and pubic hair in pubertal girls. However, reports are also available that show no association of phthalates with precocious puberty in girls. Phthalates can act through a receptor-mediated signaling pathway or affect the production of luteinizing hormone and follicle-stimulating hormone that has a direct effect on estrogen formation. Phenols like bisphenol A are industrial chemicals used mainly in the manufacture of polycarbonates and plastic materials. Bisphenol A has been shown to cause precocious puberty and earlier menarche in pubertal girls. Reports suggest that the neurotoxic effect of bisphenol A can be mediated either by competing with estradiol for binding with estrogen receptors or via the ERK/NK-kappa or ERRγ pathway. This review demonstrates the effects of phytoestrogens, phthalates, and phenols on the development of girls during puberty. PMID:24600283

Association of Van Wyk Grumbach and Debre Semelaigne Syndromes with Severe Hypothyroidism.

PubMed

Oden Akman, Alkim; Tayfun, Meltem; Demirel, Fatma; Ucakturk, Seyit Ahmed; Gungor, Ali

2015-12-01

Van Wyk Grumbach syndrome (VWGS) and Kocher-Debre Semelaigne syndrome (KDSS) are rare forms of pseudo-precocious puberty and myopathy in patients with longstanding untreated hypothyroidism. We present the case of an adolescent girl who developed pseudo-precocious puberty and myopathy caused by long-term untreated hypothyroidism. A 17-year-old female patient was referred to our outpatient clinic due to menstrual irregularities. She had muscle pain and multiple cystic ovaries in addition to clinical signs of severe congenital hypothyroidism. High levels of creatinine and creatinine kinase and accompanying muscle hypertrophy were present. After the initiation of L-thyroxine therapy, the symptoms were alleviated in a short time. Congenital and acquired hypothyroidism should be considered in the differential diagnosis of pseudo-precocious puberty and myopathy that presents with muscle pain, muscle hypertrophy, and elevated creatinine kinase levels. Copyright © 2015 North American Society for Pediatric and Adolescent Gynecology. Published by Elsevier Inc. All rights reserved.

Cyproterone acetate in treatment of precocious puberty.

PubMed Central

Kauli, R; Pertzelan, A; Prager-Lewin, R; Grünebaum, M; Laron, Z

1976-01-01

Twenty-nine children (23 girls, 6 boys) with precocious puberty were treated with cyproterone acetate for various periods of time ranging from 6 months to 3 years 4 months. They received an oral dose ranging from 70-150 mg/m2 per day, or an intramuscular depot injection once a fortnight or once a month at a dose ranging from 107-230 mg/m2. Both forms of therapy were found to suppress the signs of sexual maturation, but the oral form proved to be superior. Only the younger patients with a bone age under 11 years showed a beneficial effect upon linear growth and bone maturation. No side effects were noted, but additional advantageous effects upon behaviour and sociability were. It is concluded that at present cyproterone acetate by mouth is the drug of choice in the treatment of precocious puberty. The treatment should be initiated as early as possible to attain maximum benefit. PMID:952553

Pseudotumour Cerebri Presentation in a Child Under the Gonadotropin-Releasing Hormone Agonist Treatment

PubMed Central

Gül, Ülkü; Kaçar Bayram, Ayşe; Kendirci, Mustafa; Hatipoğlu, Nihal; Okdemir, Deniz; Gümüş, Hakan; Kurtoğlu, Selim

2016-01-01

Gonadotropin-releasing hormone analogues are common treatment option in central precocious puberty in childhood as well as in endometriosis, infertility, and prostate cancer in adults. Pseudotumor cerebri is a rare side effect observed in adults. We present the case of a girl with precocious puberty treated with triptorelin acetate who developed pseudotumor cerebri after the 4th dose. She had headaches, and her blood pressure was detected to be above the 99 percentile. There were no causes underlying of hypertension such as cardiac, renal, or endocrine. Neurological examination was normal except bilateral papilledema. Cranial magnetic resonance imaging was normal. Cerebrospinal fluid (CSF) opening pressure was elevated. Triptorelin therapy was ceased and acetazolamide was applied; CSF pressure returned to normal. We observed pseudotumor cerebri after precocious puberty treatment, a finding for the first time ever seen in childhood. PMID:27087351

A novel MKRN3 missense mutation causing familial precocious puberty.

PubMed

de Vries, L; Gat-Yablonski, G; Dror, N; Singer, A; Phillip, M

2014-12-01

Central precocious puberty may be familial in about a quarter of the idiopathic cases. However, little is known about the genetic causes responsible for the disorder. In this report we describe a family with central precocious puberty associated with a mutation in the makorin RING-finger protein 3 (MKRN3) gene. A novel missense mutation (p.H420Q) in the imprinted MKRN3 gene was identified in the four affected siblings, in their unaffected father and in his affected mother. An in silico mutant MKRN3 model predicts that the mutation p.H420Q leads to reduced zinc binding and, subsequently, impaired RNA binding. These findings support the fundamental role of the MKRN3 protein in determining pubertal timing. © The Author 2014. Published by Oxford University Press on behalf of the European Society of Human Reproduction and Embryology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Four generations in a family with neurofibromatosis 1: precocious puberty and optic nerve tumor (OPT).

PubMed

Gucev, Z; Krstevska-Konstantinova, M; Tasic, V; Jancevska, A; Kirovski, I; Pop-Jordanova, N

2010-01-01

Neurofibromatosis type 1 (NF1) is an autosomal dominant disorder with varied clinical manifestations. The proband is a 6-year-old boy with signs of precocious puberty. His penis was 10 cm, testicles 8 ml, pubic hair P2-3, and the genital skin was hyperpigmented. Multiple cafe au lait spots well above 5 mm were noticeable on his skin, as well as hard subcutaneous nodules, mostly on his trunk. His intelligence and hearing are normal. He has no history of seizures. Laboratory analysis showed: LH LH 1.4 mIU/ml, FSH 6.2 mIU/ml, testosterone 183 ng/ml. Bone age was 9 years. LHRH stimulation was characteristic of true precocious puberty (LH 9.8 mIU/ml and FSH 8.9 mIU/ml after 30 minutes). The MRI of the brain showed a tumor of the suprasellar region with compression of the pituitary stalk. At present the boy is 6 years old and has been treated with triptoreline acetate for 3 months. The volume of the testicles has decreased to 7 ml and a slight loss of pubic hair was noted. In addition, his mother and his grandfather exhibited dermal masses, and focal cutaneous and subcutaneous growths. The great-grand father had had the same cutaneous changes and died at the age of 75 from unrelated causes. It has already been well documented that NF is associated with an increased risk of malignancy and precocious puberty. Hence, we emphasize the need for a close and regular clinical follow-up of the OPT, puberty and patterns of growth.

Treatment of true precocious puberty with a potent luteinizing hormone-releasing factor agonist: effect on growth, sexual maturation, pelvic sonography, and the hypothalamic-pituitary-gonadal axis.

PubMed

Styne, D M; Harris, D A; Egli, C A; Conte, F A; Kaplan, S L; Rivier, J; Vale, W; Grumbach, M M

1985-07-01

We used the LHRH agonist D-Trp6-Pro6-N-ethylamide LHRH (LHRH-A) to treat 19 children (12 girls and 7 boys) with true precocious puberty. Fourteen patients had idiopathic true precocious puberty, 4 had a hamartoma of the tuber cinereum, and 1 had a hypothalamic astrocytoma. Basal gonadotropin secretion and responses to native LHRH decreased within 1 week of initiation LHRH-A therapy, and sex steroid secretion decreased within 2 weeks to or within the prepubertal range. Ultrasonographic evaluation of the uterus indicated a postmenarchal size and shape in all 11 girls studied before treatment, which reverted to prepubertal size and configuration in 5 girls during LHRH-A therapy. The enlarged ovaries decreased in size and the multiple ovarian follicular cysts regressed. Sexual characteristics ceased advancing or reverted toward the prepubertal state in all patients receiving therapy for 6-36 months. All 5 girls with menarche before therapy had no further menses. Three girls had hot flashes after LHRH-A-induced reduction of the plasma estradiol concentration. Height velocity, SDs above the mean height velocity for age, and SDs above the mean height for age decreased during LHRH-A therapy; the velocity of skeletal maturation decreased after 12 months of LHRH-A therapy and was sustained during continued therapy over 18-36 months. In 4 patients, a subnormal growth rate (less than 4.5 cm/yr) occurred during LHRH-A therapy. Six patients had cutaneous reactions of LHRH-A, but no demonstrable circulating antibodies to LHRH-A. In 2 patients in whom LHRH-A therapy was discontinued because of skin reactions, precocious sexual maturation resumed at the previous rate for the ensuing 6-12 months; subsequently, they were desensitized to LHRH-A, and during a second course of therapy, their secondary sexual development and sex steroid levels again quickly decreased. LHRH-A proved an effective and safe treatment for true precocious puberty in boys as well as girls with central precocious puberty whether of the idiopathic type or secondary to a hamartoma of the tuber cinereum or a hypothalamic neoplasm.

Precocious Puberty

MedlinePlus

... puberty begins between ages 8 and 12 in girls and between 9 and 14 in boys. Hormones ... sex hormones. The sex hormones, especially estrogen in girls and testosterone in boys, cause sexual maturation. What ...

Consensus statement on the use of gonadotropin-releasing hormone analogs in children.

PubMed

Carel, Jean-Claude; Eugster, Erica A; Rogol, Alan; Ghizzoni, Lucia; Palmert, Mark R; Antoniazzi, Franco; Berenbaum, Sheri; Bourguignon, Jean-Pierre; Chrousos, George P; Coste, Joël; Deal, Sheri; de Vries, Liat; Foster, Carol; Heger, Sabine; Holland, Jack; Jahnukainen, Kirsi; Juul, Anders; Kaplowitz, Paul; Lahlou, Najiba; Lee, Mary M; Lee, Peter; Merke, Deborah P; Neely, E Kirk; Oostdijk, Wilma; Phillip, Moshe; Rosenfield, Robert L; Shulman, Dorothy; Styne, Dennis; Tauber, Maïthé; Wit, Jan M

2009-04-01

Gonadotropin-releasing hormone analogs revolutionized the treatment of central precocious puberty. However, questions remain regarding their optimal use in central precocious puberty and other conditions. The Lawson Wilkins Pediatric Endocrine Society and the European Society for Pediatric Endocrinology convened a consensus conference to review the clinical use of gonadotropin-releasing hormone analogs in children and adolescents. When selecting the 30 participants, consideration was given to equal representation from North America (United States and Canada) and Europe, an equal male/female ratio, and a balanced spectrum of professional seniority and expertise. Preference was given to articles written in English with long-term outcome data. The US Public Health grading system was used to grade evidence and rate the strength of conclusions. When evidence was insufficient, conclusions were based on expert opinion. Participants were put into working groups with assigned topics and specific questions. Written materials were prepared and distributed before the conference, revised on the basis of input during the meeting, and presented to the full assembly for final review. If consensus could not be reached, conclusions were based on majority vote. All participants approved the final statement. The efficacy of gonadotropin-releasing hormone analogs in increasing adult height is undisputed only in early-onset (girls <6 years old) central precocious puberty. Other key areas, such as the psychosocial effects of central precocious puberty and their alteration by gonadotropin-releasing hormone analogs, need additional study. Few controlled prospective studies have been performed with gonadotropin-releasing hormone analogs in children, and many conclusions rely in part on collective expert opinion. The conference did not endorse commonly voiced concerns regarding the use of gonadotropin-releasing hormone analogs, such as promotion of weight gain or long-term diminution of bone mineral density. Use of gonadotropin-releasing hormone analogs for conditions other than central precocious puberty requires additional investigation and cannot be suggested routinely.

McCune-Albright syndrome associated with pituitary microadenoma: patient report.

PubMed

Chen, Chun-Jung; Liu, Jah-Yao; Cheng, Shin-Nan; Chang, Fung-Wei; Yuh, Yeong-Seng

2004-03-01

McCune-Albright syndrome (MAS) is a rare disorder characterized by the classic triad of precocious puberty, polyostotic fibrous dysplasia and café-au-lait spots. Additional endocrine abnormalities may also be present, including hyperthyroidism, growth hormone excess and hyperprolactinemia. The most commonly encountered endocrine dysfunction is gonadal hyperfunction. Gonadotropin-independent precocious puberty is typically the initial manifestation of MAS in girls. Ovarian cysts may be detected on pelvic ultrasound. Our patient was also found to have pituitary microadenoma, evidenced by dynamic magnetic resonance imaging.

Successful treatment of hyperphagia by resection of a hypothalamic hamartoma.

PubMed

Esquenazi, Yoshua; Sandberg, David I; Rekate, Harold L

2013-06-01

Hypothalamic hamartomas (HHs) are benign lesions that are often associated with central precocious puberty and may present with gelastic seizures. Treatment modalities for HH include medical therapy with long-term gonadotropin-releasing hormone analogs or resection. The authors report the case of a 7-year-old girl who was diagnosed with an HH due to precocious puberty and was treated medically with a gonadotropin-releasing hormone analog for 3 years. Despite normalization of her plasma levels of luteinizing hormone, follicle-stimulating hormone, and estradiol and arrest of her precocious puberty, the patient developed progressive weight gain associated with extreme hyperphagia and morbid obesity by the age of 10 years. Her compulsive eating patterns were refractory to counseling and other interventions attempted by her parents and physicians. After resection of the HH, her hyperphagia resolved and her weight stabilized. To the authors' knowledge, this is the first report describing resection of an HH for the purpose of treating hyperphagia and obesity.

Testosterone Test

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... Cancer Therapy Glucose Tests Gonorrhea Testing Gram Stain Growth Hormone Haptoglobin hCG Pregnancy hCG Tumor Marker HDL Cholesterol ... Puberty. PDF available for download at http://www.hormone.org/Resources/Growth/upload/bilingual_precocious_puberty.pdf. Accessed January 2009. ...

How Do Health Care Providers Diagnose Precocious Puberty and Delayed Puberty?

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Idiopathic precocious puberty in girls: Psychosexual development.

PubMed

Meyer-Bahlburg, H F; Ehrhardt, A A; Bell, J J; Cohen, S F; Healey, J M; Feldman, J F; Morishima, A; Baker, S W; New, M I

1985-08-01

A promising model syndrome for the examination of the role of physical maturation in the development of female sexuality is idiopathic precocious puberty (IPP). In this first controlled study of psychosexual development in IPP females, 16 females between 13 and 20 years of age with a history of IPP were compared to 16 control subjects with a history of normal puberty pair-matched to the index subjects on the basis of sex, race, age, socioeconomic level, and menarcheal status. The psychosexual history and the current psychosexual status were assessed by a systematic half-structured interview. The IPP females on average passed the psychosexual milestones at an earlier age than their normal maturing peers, with a particularly early onset of masturbation. Those who were sociosexually active tended to report a higher total orgasmic outlet and a higher sex drive. There was no increase in homosexuality among IPP girls. The timing of puberty has a (modest) influence on psychosexual development in females.

Plasma concentrations of osteocalcin are associated with the timing of pubertal progress in boys.

PubMed

Schündeln, Michael M; Bäder, Lena; Kiewert, Cordula; Herrmann, Ralf; Führer, Dagmar; Hauffa, Berthold P; Grasemann, Corinna

2017-02-01

Animal models have shown that the skeletal hormone osteocalcin stimulates testicular testosterone synthesis. To assess whether osteocalcin might be a useful marker to detect pubertal development disorders, we examined osteocalcin plasma concentrations in children and adolescents with and without disorders of pubertal development. Osteocalcin concentrations were investigated in a total of 244 patients with endocrine disorders (122 males, mean age: 11.87+3.77 years), including patients with precocious puberty and constitutional delay of puberty. Osteocalcin concentrations were highest among adolescents with precocious puberty and advanced pubertal development (120.60±45.22 ng/mL), while the concentrations were lowest among patients with constitutional delay of puberty (102.20±37.13 ng/mL). Overall, osteocalcin concentrations were strongly correlated with markers of bone metabolism. Although plasma osteocalcin concentrations are associated with pubertal development in boys, it does not appear to be a useful diagnostic marker for altered pubertal development.

Precocious puberty and large multicystic ovaries in young girls with primary hypothyroidism.

PubMed

Sanjeevaiah, Aravind Raj; Sanjay, Subbarayappa; Deepak, Tejesweni; Sharada, Ardanareshwaran; Srikanta, Sri S

2007-10-01

To describe 2 cases of primary hypothyroidism, precocious puberty, large multicystic ovaries, possible diagnostic dilemma, unilateral oophorectomies, and subsequent response to levothyroxine replacement therapy. We present the clinical, biochemical, radiologic, and histopathologic findings in 2 patients with rare cases of Van Wyk-Grumbach syndrome and megaovaries, who underwent unilateral oophorectomy. Two patients, an 8-year-old girl and a 3-year-old girl (cases 1 and 2, respectively), were referred to our center. Both patients presented with precocious puberty and vaginal bleeding and had undergone unilateral oophorectomy before referral. In the first patient (case 1), the surgical intervention was a consequence of torsion of the left megaovary, necessitating emergency oophorectomy. Oophorectomy in the second patient (case 2) was a result of initial diagnostic confusion, inasmuch as a sexcord stromal tumor was suspected. A detailed history, physical examination, and laboratory results pointed toward primary hypothyroidism due to Hashimoto's thyroiditis and thyroid dysgenesis, respectively. Serial ultrasound studies of the abdomen and pelvis revealed large multicystic ovaries, with progressive enlargement (including regrowth from an apparent ovarian "postsurgical remnant"). Both patients responded dramatically after initiation of levothyroxine replacement therapy, with no further vaginal bleeding and reversal of megaovary to normal size (in case 1). In a highly selected minority of children with untreated primary hypothyroidism, there is development of precocious puberty and progressively enlarging multicystic ovaries. The precise endocrine, neuroanatomic, and neurophysiologic bases for this phenomenon are unclear. Nevertheless, the entire clinicopathologic picture, including giant ovaries, dramatically reverts to normal status with the restoration of a euthyroid state by means of simple levothyroxine replacement therapy.

Treatment of central precocious puberty by subcutaneous injections of leuprorelin 3-month depot (11.25 mg).

PubMed

Carel, Jean-Claude; Lahlou, Najiba; Jaramillo, Orlando; Montauban, Vincent; Teinturier, Cécile; Colle, Michel; Lucas, Christel; Chaussain, Jean Louis

2002-09-01

Depot GnRH agonists are widely used for the treatment of precocious puberty. Leuprorelin 3-month depot is currently used in adults but has not been evaluated in children. We evaluated the efficacy of this new formulation (11.25 mg every 3 months), for the suppression of gonadotropic activation and pubertal signs in children with central precocious puberty. We included 44 children (40 girls) with early-onset pubertal development in a 6-month open trial. The inclusion criteria were clinical pubertal development before the age of 8 (girls) or 10 (boys), advanced bone age, enlarged uterus (>36 mm), testosterone more than 1.7 nmol/liter (boys), and pubertal response of LH to GnRH (peak >5 IU/liter). The principal criterion for efficacy assessment, GnRH-stimulated LH peak less than 3 IU/liter, was met in 81 of 85 (95%) of the tests performed at months 3 and 6. The remaining four values were slightly above the threshold. The levels of sex steroids were also significantly reduced and clinical pubertal development was arrested. Plasma leuprorelin levels, measured every 30 d, were essentially stable after d 60. Local intolerance was noted after 10 of 86 injections (12%), and was mild in four cases, moderate in five cases, and severe in one. Among these 10 events, 4 consisted in local pain at injection's site. In conclusion, leuprorelin 3-month depot efficiently inhibits the gonadotropic axis in 95% of children with central precocious puberty studied for a 6-month period. This regimen allows the reduction of the number of yearly injections from 12 to 4.

Growth hormone deficiency: an unusual presentation of floating harbor syndrome.

PubMed

Galli-Tsinopoulou, Assimina; Kyrgios, Ioannis; Emmanouilidou, Eleftheria; Maggana, Ioanna; Kotanidou, Eleni; Kokka, Paraskevi; Stylianou, Charilaos

2011-01-01

Floating-Harbor Syndrome (FHS) is a very rare condition of unknown etiology characterized by short stature, delayed bone age, characteristic facial features, delayed language skills and usually normal motor development. This syndrome has only once been associated with growth hormone deficiency and precocious puberty in the same patient. We describe a 5 4/12 year-old girl with the typical features of FHS in whom growth hormone deficiency was diagnosed and two years later central precocious puberty was noted. The patient showed a good response to human recombinant growth hormone as well as gonadotropin releasing hormone analogue treatment.

Prenatal stress increases adult vulnerability to cocaine reward without affecting pubertal anxiety or novelty response.

PubMed

Pastor, Verónica; Pallarés, María Eugenia; Antonelli, Marta C

2018-02-26

Prenatal stress (PS) induces long-lasting molecular alterations in brain circuits of the offspring and increases the propensity to develop neuropsychiatric diseases during adulthood, including mood disorders and drug addiction. A major goal of this study was to assess the impact of PS on pubertal behaviour and adult vulnerability to cocaine-induced conditioning place preference (CPP). We therefore evaluated pubertal novelty response and anxiety-like behaviour in control (C) and PS rats, and then, we examined cocaine-induced CPP in those animals during adulthood. We found no differences between C and PS groups on pubertal behaviour, however, only PS rats showed a significant cocaine-induced CPP. To further analyze our results, we classified cocaine-treated rats regarding their CPP score in Low CPP or High CPP and we then analysed their pubertal behaviour. We found different relations of anxiety-like behaviour to cocaine reward as a function of PS exposure: for C group, High CPP and Low CPP had shown similar levels of anxiety-like behaviour at puberty; on the contrary, for PS group, High CPP had shown lower anxiety-like behaviour than Low CPP rats. This study underscores the importance of considering prenatal exposure to stress when analysing the relationship between anxiety and cocaine vulnerability. Moreover, the evaluation of behavioural traits at puberty opens the possibility of early intervention and will allow the development of specific prevention strategies to avoid the devastating consequences of drug addiction later in life. Copyright © 2017 Elsevier B.V. All rights reserved.

A new efficient method to monitor precocious puberty nationwide in France.

PubMed

Rigou, Annabel; Le Moal, Joëlle; Léger, Juliane; Le Tertre, Alain; Carel, Jean-Claude

2018-02-01

Clinical precocious puberty (PP) is a disease, reputed to be on the increase and suspected to be linked to endocrine disrupting chemicals (EDC) exposure. Population-based epidemiological data are lacking in France and scarce elsewhere. We accessed the feasibility of monitoring PP nationwide in France in this context, using a nationwide existing database, the French National Health Insurance Information System. Here, we present the method we used with a step-by-step approach to build and select the most suitable indicator. We built three indicators reflecting the incidence of idiopathic central precocious puberty (ICPP), the most frequent form of PP, and we compared these indicators according to their strengths and weaknesses with respect to surveillance purposes. Monitoring ICPP in France proved feasible using a Drug reimbursement indicator. Our method is cost efficient and highly relevant in public health surveillance. Our step-by-step approach proved helpful to achieve this project and could be proposed for assessing the feasibility of monitoring health outcomes of interest using existing data bases. What is known: • Precocious puberty (PP) is suspected to be related to EDC exposure and it is believed to be on the increase in France and in others countries. • Very few epidemiologic data on PP are currently available in the world at the national scale. What is new: • This is the first study describing a method to monitor the most frequent form of PP, idiopathic central PP (ICPP) nationwide in a cost-efficient way, using health insurance databases. • This cost-effective method will allow to estimate and monitor the incidence of ICPP in France and to analyze spatial variations at a very precise scale, which will be very useful to examine the role of environmental exposures, especially to EDCs.

Do internationally adopted children in the Netherlands use more medication than their non-adopted peers?

PubMed

van Ginkel, Joost R; Juffer, Femmie; Bakermans-Kranenburg, Marian J; van IJzendoorn, Marinus H

2016-05-01

Empirical evidence has shown that international adoptees present physical growth delays, precocious puberty, behavioral problems, and mental health referrals more often than non-adoptees. We hypothesized that the higher prevalence of (mental) health problems in adoptees is accompanied by elevated consumption of prescription drugs, including antidepressants, attention deficit hyperactivity disorder (ADHD) medication, and medication for growth inhibition/stimulation. In an archival, population-based Dutch cohort study, data on medication use were available from the Health Care Insurance Board by Statistics Netherlands from 2006 to 2011. The Dutch population born between 1994 and 2005 and alive during the period of measurement was included (2,360,450 including 10,602 international adoptees, of which 4447 from China). Their mean age was 6.5 years at start (range 1-12 years) and 11.5 years at the end of the measurement period (range 6-17 years). Chinese female adoptees used less medication for precocious puberty (as treatment for precocious puberty; odds ratio (OR) = 0.57, effect size Cohen's d = -0.31) and contraception (OR = 0.65, d = -0.24) than non-adoptees. For both males and females, non-Chinese adoptees used more medication for ADHD than non-adoptees (males: OR = 1.22, females: OR = 1.32), but the effect was small (males: d = 0.11, females: d = 0.15). Adoptees in the Netherlands generally do not use more medication than their non-adopted peers. • Meta-analytical evidence shows that international adoptees present physical growth delays and mental health referrals more often than non-adopted controls. • With the exception of one Swedish study on ADHD medication, there is no other systematic research on medication use of international adoptees. What is New: • All differences in medication use between international adoptees in the Netherlands and non-adopted controls were below the threshold of a small effect with the exception of medication for precocious puberty, but this effect was in the opposite direction with female adoptees using less medication for precocious puberty than non-adoptees. • International adoptees in the Netherlands do not use more medication despite experiences of preadoption adversity and higher rates of mental health referrals during childhood and adolescence.

The Effect of Bisphenol A on Puberty: A Critical Review of the Medical Literature.

PubMed

Leonardi, Alberto; Cofini, Marta; Rigante, Donato; Lucchetti, Laura; Cipolla, Clelia; Penta, Laura; Esposito, Susanna

2017-09-10

Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As an explanation, some authors have considered the global socio-economic improvement across different populations, and other authors have considered the action of endocrine disrupting chemicals (EDCs). Among these, bisphenol A (BPA), an aromatic compound largely used worldwide as a precursor of some plastics and chemical additives, is well known for its molecular oestrogen-like and obesogenic actions. We reviewed the medical literature of the previous 20 years that examined associations between BPA exposure and the age of puberty in humans, considering only those referring to clinical or epidemiological data. Of 19 studies, only 7 showed a correlation between BPA and puberty. In particular, the possible disruptive role of BPA on puberty may be seen in those with central precocious puberty or isolated premature breast development aged 2 months to 4 years old, even if the mechanism is undefined. Some studies also found a close relationship between urinary BPA, body weight, and early puberty, which can be explained by the obesogenic effect of BPA itself. The currently available data do not allow establishment of a clear role for BPA in pubertal development because of the conflicting results among all clinical and epidemiological studies examined. Further research is needed to fully understand the potential role of exposure to EDCs and their adverse endocrine health outcomes.

The Effect of Bisphenol A on Puberty: A Critical Review of the Medical Literature

PubMed Central

Leonardi, Alberto; Cofini, Marta; Lucchetti, Laura; Cipolla, Clelia; Penta, Laura

2017-01-01

Many scientific studies have revealed a trend towards an earlier onset of puberty and have disclosed an increasing number of children that display precocious puberty. As an explanation, some authors have considered the global socio-economic improvement across different populations, and other authors have considered the action of endocrine disrupting chemicals (EDCs). Among these, bisphenol A (BPA), an aromatic compound largely used worldwide as a precursor of some plastics and chemical additives, is well known for its molecular oestrogen-like and obesogenic actions. We reviewed the medical literature of the previous 20 years that examined associations between BPA exposure and the age of puberty in humans, considering only those referring to clinical or epidemiological data. Of 19 studies, only 7 showed a correlation between BPA and puberty. In particular, the possible disruptive role of BPA on puberty may be seen in those with central precocious puberty or isolated premature breast development aged 2 months to 4 years old, even if the mechanism is undefined. Some studies also found a close relationship between urinary BPA, body weight, and early puberty, which can be explained by the obesogenic effect of BPA itself. The currently available data do not allow establishment of a clear role for BPA in pubertal development because of the conflicting results among all clinical and epidemiological studies examined. Further research is needed to fully understand the potential role of exposure to EDCs and their adverse endocrine health outcomes. PMID:28891963

Complete virilization in congenital adrenal hyperplasia: clinical course, medical management and disease-related complications.

PubMed

Woelfle, J; Hoepffner, W; Sippell, W G; Brämswig, J H; Heidemann, P; Deiss, D; Bökenkamp, A; Roth, C; Irle, U; Wollmann, H A; Zachmann, M; Kubini, K; Albers, N

2002-02-01

In girls with congenital adrenal hyperplasia (CAH), genital ambiguity usually leads to a rapid neonatal diagnosis. Rarely, CAH causes complete virilization and male sex assignment with a delayed diagnosis. After being confronted with very specific problems in two of such patients, we collected data of patients with CAH and complete virilization in a nationwide study to delineate specific problems of these rare patients in order to improve their management. Through the German Working Group of Paediatric Endocrinology (Arbeitsgemeinschaft Pädiatrische Endokrinologie, APE), questionnaires were sent to all members caring for patients with CAH and complete virilization in their endocrine clinics. Data from 16 patients from 10 paediatric endocrine centres were assessed by questionnaire. The following problems have been encountered. (1) Sex assignment/gender identity: initially all patients had a male sex assignment. Six patients were diagnosed during the first month of life. Five were reassigned to female sex immediately, one at the age of 19 months. Except in one girl demonstrating some tomboyish behaviour, gender role behaviour in these patients did not differ from unaffected girls. Ten patients were diagnosed late at 3.4--7 years of age. In seven patients with a late diagnosis, male sex assignment was maintained; one of them expressed some concerns about living as a male. In three patients late sex reversal was performed, gender identity is very poor in one and new sex assignment is currently under consideration. (2) SURGERY: irrespective of the sex assigned, all patients had between one and three surgical procedures, including clitoris reduction and (repeated) vaginoplasties in patients with female sex assignment. Hysterectomy and ovarectomy were performed in patients with male sex assignment. (3) Short stature: patients with a late diagnosis of CAH had extremely advanced bone ages of +6.3 to +9.5 years, leading to severely reduced final height of 137 to 150 cm in adult patients. Patients tended to follow height percentiles of genetic females. One pubertal patient was suicidal due to short stature. (4) Central precocious puberty (CPP): prolonged exposition to adrenal androgens led to CPP in one patient. He was treated with GnRH analogues until gonadectomy. Patients with CAH and complete virilization have a high risk of being diagnosed late. There are major problems and uncertainties of the patients' families and the treating physicians concerning gender assignment. Gender identity is disturbed in some patients. In addition, multiple surgical procedures are necessary and short stature as well as central precocious puberty might be important to avoid late sequelae. While some surgical interventions are probably unavoidable, most of these issues could be resolved with an early diagnosis. Thus, especially for these patients, a neonatal screening programme for CAH would be of paramount importance.

[Rapidly progressive puberty in a patient with mosaic Turner syndrome: a case report and literature review].

PubMed

Liang, Y; Wei, H; Yu, X; Huang, W; Luo, X P

2017-02-02

Objective: To explore the clinical characteristics of diagnosis and treatment in patients with Turner syndrome and rapidly progressive puberty. Method: A rare case of rapidly progressive puberty in Turner syndrome with a mosaic karyotype of 45, X/46, X, del(X)(p21)(80%/20%)was diagnosed at Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology in January. 2015. Clinical characteristics and the related literature were reviewed. Original papers on precocious puberty or rapidly progressive puberty in Turner syndrome, published until Apr. 2016 were retrieved at PubMed and CNKI databases by the use of the key words "Turner syndrome" , "precocious puberty" and "rapidly progressive puberty" . Result: The patient was born at term with birth weight of 2 450 g and was diagnosed with SGA at 3 years of age for the first evaluating of growth and development. Then recombined human growth hormone (rhGH )was given at 4 years of age due to short stature (height<3 percentile) and low growth velocity(<5.0 cm/year) as well. However, rhGH treatment was discontinued after 9 months because of economic burdens. Breast development was noted at 9 years and 3 months. The patient was followed up at 3 months intervals. Physical examination revealed a Tanner stage Ⅲ breast development at 10.33 years , the bone age was 11.6 years. Then, gonadotropin-releasing hormone analogs treatment was added to slow pubertal progression and to preserve maximum adult height. The growth rate decreased with therapy from 7.5 cm/year to 4.4 cm/year. The patient was reevaluated, and the chromosome analysis of peripheral blood revealed a mosaic karyotype 45, X/46, X, del(X)(p21)(80%/ 20%). To date, only 10 cases have been reported in the literature. Six of them showing mosaic TS, three karyotypes with structural abnormality of short arm of X chromosome, one with the karyotype 45, X. Conclusion: It is the first time that rapidly progressive puberty in a 45, X/46, X, del(X)(p21) mosaic Turner syndrome is reported. Although short stature and ovarian dysgenesis are common in TS, precocious puberty may occur in TS, which is liable to cause delayed diagnosis and misdiagnosis. Careful examination is recommended for patients with unusual growth pattern, even though girls have normal height in accord with standard growth curve or spontaneous puberty. Evaluation for TS and subsequent investigation should be prompted.

Effects of early menarche on physical and psychosocial health problems in adolescent girls and adult women

PubMed Central

2016-01-01

The menarcheal age of Korean women has been rapidly decreasing for the last 50 years, and the average menarcheal age of women born in the 1990s is approaching 12.6 years. In addition, interest in early puberty has been increasing recently owing to the rapid increase in precocious puberty. Generally, out of concern for short stature and early menarche, idiopathic central precocious puberty in female adolescents is treated with gonadotropin-releasing hormone analogs. Studies to date have described the association between early menarche and psychosocial problems such as delinquency and risky sexual behavior, as well as physical health problems such as obesity, diabetes, cardiovascular diseases, and breast cancer throughout the lifespan of women. However, the pathophysiological mechanism underlying this association has not been clarified thus far. In this article, we review and discuss the existing literature to describe the current understanding of the effects of early menarche on the physical and psychosocial health of adolescent girls and adult women. PMID:27721839

A case of atypical McCune-Albright syndrome requiring optic nerve decompression.

PubMed

Yavuzer, R; Khilnani, R; Jackson, I T; Audet, B

1999-10-01

McCune-Albright syndrome (MAS) is a disease of noninheritable, genetic origin defined by the triad of café-au-lait pigmentation of the skin, precocious puberty, and polyostotic fibrous dysplasia. This syndrome, which affects young girls primarily, has also been reported with other endocrinopathies, and rarely with acromegaly and hyperprolactinemia. The fibrous dysplasia in MAS is of the polyostotic type and, apart from the characteristic sites such as the proximal aspects of the femur and the pelvis, the craniofacial region is frequently involved. A male patient with MAS presented with juvenile gigantism, precocious puberty, pituitary adenoma-secreting growth hormone and prolactin, hypothalamic pituitary gonadal and thyroid dysfunction, and polyostotic fibrous dysplasia causing optic nerve compression. Visual deterioration and its surgical management are presented.

A missense mutation in MKRN3 in a Danish girl with central precocious puberty and her brother with early puberty.

PubMed

Känsäkoski, Johanna; Raivio, Taneli; Juul, Anders; Tommiska, Johanna

2015-12-01

Idiopathic central precocious puberty (ICPP) results from the premature reactivation of the hypothalamic-pituitary-gonadal axis leading to development of secondary sexual characteristics prior to 8 y in girls or 9 y in boys. Since the initial discovery of mutations in the maternally imprinted MKRN3 gene in 2013, several case reports have described mutations in this gene in ICPP patients from different populations, highlighting the importance of MKRN3 as a regulator of pubertal onset. We screened 29 Danish girls with ICPP for mutations in MKRN3. Expression of MKRN3 in human hypothalamic complementary DNA (cDNA) was investigated by PCR. One paternally inherited rare variant, c.1034G>A (p.Arg345His), was identified in one girl with ICPP and in her brother with early puberty. The variant is predicted to be deleterious by three different in silico prediction programs. Expression of MKRN3 was confirmed in adult human hypothalamus. Our results are in line with previous studies in which paternally inherited MKRN3 mutations have been found both in males and in females with ICPP or early puberty. Our report further expands the set of MKRN3 mutations identified in ICPP patients across diverse populations, thus supporting the major regulatory function of MKRN3 in pubertal onset.

Premature pubarche before one year of age: distinguishing between mini-puberty variants and precocious puberty.

PubMed

Bourayou, Rafik; Giabicani, Eloïse; Pouillot, Monique; Brailly-Tabard, Sylvie; Brauner, Raja

2015-04-02

The aim of this study was to facilitate the distinction between the benign "mini-puberty of early infancy" and precocious puberty (PP). We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP. The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations. Their gonadotropin responses to gonadotropin releasing hormone (GnRH) test showed predominant luteinising hormone increase in 9/13. The girls presented with pubic hair development that was accompanied by breast development in 47% of cases, with low plasma estradiol concentrations. Their gonadotropin responses showed predominant follicle-stimulating hormone increase in the 17 evaluated. The patients with PP had organic central PP (5 hypothalamic hamartoma) or idiopathic central PP (n=6), or peripheral PP (one ovarian tumor and one congenital adrenal hyperplasia). The diagnosis was challenging only in 3 girls with idiopathic central PP presenting with prepubertal plasma estradiol concentrations and responses to GnRH test. The diagnosis of PP was easily determined based on the clinical presentation and the pubertal concentrations of testosterone in boys or of estradiol in girls, as was the diagnosis of central or peripheral origin of PP based on gonadotropin response to the GnRH test. Once PP is excluded, these patients need careful follow-up and physician consultation is needed if clinical pubertal signs progress.

Premature Pubarche before One Year of Age: Distinguishing between Mini-Puberty Variants and Precocious Puberty

PubMed Central

Bourayou, Rafik; Giabicani, Eloïse; Pouillot, Monique; Brailly-Tabard, Sylvie; Brauner, Raja

2015-01-01

Background The aim of this study was to facilitate the distinction between the benign “mini-puberty of early infancy” and precocious puberty (PP). Material/Methods We compared 59 patients (21 boys and 38 girls) seen for pubic hair development before one year of age diagnosed as mini-puberty to 13 patients (2 boys) in whom pubertal development before one year revealed a PP. Results The boys with mini-puberty presented with pubic hair development and prepubertal testicular volume, with low plasma testosterone concentrations. Their gonadotropin responses to gonadotropin releasing hormone (GnRH) test showed predominant luteinising hormone increase in 9/13. The girls presented with pubic hair development that was accompanied by breast development in 47% of cases, with low plasma estradiol concentrations. Their gonadotropin responses showed predominant follicle-stimulating hormone increase in the 17 evaluated. The patients with PP had organic central PP (5 hypothalamic hamartoma) or idiopathic central PP (n=6), or peripheral PP (one ovarian tumor and one congenital adrenal hyperplasia). The diagnosis was challenging only in 3 girls with idiopathic central PP presenting with prepubertal plasma estradiol concentrations and responses to GnRH test. Conclusions The diagnosis of PP was easily determined based on the clinical presentation and the pubertal concentrations of testosterone in boys or of estradiol in girls, as was the diagnosis of central or peripheral origin of PP based on gonadotropin response to the GnRH test. Once PP is excluded, these patients need careful follow–up and physician consultation is needed if clinical pubertal signs progress. PMID:25832117

A Study on Dietary Habits and Lifestyle of Girls with Precocious Puberty

PubMed Central

Heo, Jae-Seong; Moon, Hyeok-Soo

2016-01-01

Purpose This study was conducted to analyze the change in the obesity index in girls receiving a gonadotropin-releasing hormone agonist (GnRHa), based on treatment duration, and to aid in nutritional counseling by investigating dietary habits and lifestyle. Methods Anthropometric examinations were conducted on 62 girls treated with GnRHa from January 2010 through July 2014. Parents were asked to fill out questionnaires on patient dietary habits and lifestyle. Results The group taking GnRHa for over 1 year had a higher rate of obesity increase than the group taking GnRHa for less than 1 year, but they had common habits related to obesity, which should be corrected. In addition, 69.2% of the normal weight group taking GnRHa for over 1 year gained weight, and needed more intensive programs, which include physical exercise and nutritional education. Although girls with precocious puberty showed a decrease in the intake of high-calorie foods with nutritional intervention regardless of treatment duration, they still had problems that needed improvement, such as shorter meals and lack of exercise. Conclusion Girls with precocious puberty and their parents should emphasize maintenance of proper body weight, especially when treatment for over 1 year is anticipated. Consistent education in nutrition, ways to increase intensity and duration of physical activity, and the need to slow down mealtimes are important in managing obesity; doctors need to perform regular checkups and provide nutritional counseling. PMID:27437190

Herbal medicine for idiopathic central precocious puberty: A protocol for a systematic review of controlled trials.

PubMed

Lee, Hye Lim; Lee, Yoo Been; Choi, Jun-Yong; Lee, Ju Ah

2018-03-01

Herbal medicine is widely used in East Asia to treat idiopathic central precocious puberty (ICPP). Most of the available clinical trials that investigated herbal medicine for ICPP have been included in this review. This systematic review will assess the efficacy and safety of herbal medicine for ICPP. Eleven databases, including Asian databases, will be searched for studies conducted through 2018. We will include randomized controlled trials assessing herbal medicine for ICPP. The risk of bias will be evaluated using the Cochrane risk of bias assessment tool, and confidence in the cumulative evidence will be evaluated using the Grading of Recommendations Assessment, Development, and Evaluation instrument. This systematic review will be published in a peer-reviewed journal and disseminated both electronically and in print. The review will be updated to inform and guide health care practices. PROSPER 2018 CRD42018087988.

Progressive central puberty in a toddler with partial androgen insensitivity.

PubMed

Dougan, Grace C; Uli, Naveen; Shulman, Dorothy I

2014-03-01

A male infant was diagnosed with partial androgen insensitivity caused by a novel mutation in the androgen receptor. At 3.5 months of age, he received 100 mg of testosterone intramuscularly over the course of 3 months to increase phallic size. He developed pubic hair after 5 months and signs of progressive central precocious puberty when re-examined at 17.5 months, which subsequently was suppressed with depot leuprolide. Copyright © 2014 Mosby, Inc. All rights reserved.

Luteinizing hormone-releasing hormone analogue (Buserelin) treatment for central precocious puberty: a multi-centre trial.

PubMed

Werther, G A; Warne, G L; Ennis, G; Gold, H; Silink, M; Cowell, C T; Quigley, C; Howard, N; Antony, G; Byrne, G C

1990-02-01

A multi-centre open trial of Buserelin, a luteinizing hormone-releasing hormone (LHRH) analogue, was conducted in 13 children with central precocious puberty. Eleven children (eight girls and three boys), aged 3.4-10.2 years at commencement, completed the required 12 month period of treatment. Initially all patients received the drug by intranasal spray in a dose of 1200 micrograms/day, but by the end of the 12 month period two were having daily subcutaneous injections and three were receiving an increased dose intranasally. The first month of treatment was associated in one boy with increased aggression and masturbation, and in the girls with an increase in the prevalence of vaginal bleeding. Thereafter, however, both behavioural abnormalities and menstruation were suppressed. Median bone age increased significantly during the study, but without any significant change in the ratio of height age to bone age. The median predicted adult height for the group therefore did not alter significantly over the twelve months of the study. Buserelin treatment caused a reduction in the peak luteinizing hormone and follicle-stimulating hormone (FSH) responses to LHRH, mostly to prepubertal levels, and also suppressed basal FSH. In the first weeks of treatment, the girls' serum oestradiol levels rose significantly and then fell to prepubertal or early pubertal levels. A similar pattern was seen for serum testosterone levels. Serum somatomedin-C levels, however, showed little fluctuation over the course of the study. Buserelin treatment was safe and well accepted, and offers the promise of improved linear growth potential in precocious puberty.

Manganese induces IGF-1 and cyclooxygenase-2 gene expressions in the basal hypothalamus during prepubertal female development.

PubMed

Hiney, Jill K; Srivastava, Vinod K; Dees, William Les

2011-06-01

Precocious puberty is a significant child health problem, especially in girls, because 95% of cases are idiopathic. Our earlier studies demonstrated that low-dose levels of manganese (Mn) caused precocious puberty via stimulating the secretion of luteinizing hormone-releasing hormone (LHRH). Because glial-neuronal communications are important for the activation of LHRH secretion at puberty, we investigated the effects of prepubertal Mn exposure on specific glial-derived puberty-related genes known to affect neuronal LHRH release. Animals were supplemented with MnCl(2) (10 mg/kg) or saline by gastric gavage from day 12 until day 22 or day 29, then decapitated, and brains removed. The site of LHRH release is the medial basal hypothalamus (MBH), and tissues from this area were analyzed by real-time PCR for transforming growth factor α (TGFα), insulin-like growth factor-1 (IGF-1), and cyclooxygenase-2 (COX-2) messenger RNA levels. Protein levels for IGF-1 receptor (IGF-1R) were measured by Western blot analysis. LHRH gene expression was measured in the preoptic area/anteroventral periventricular (POA/AVPV) region. In the MBH, at 22 days, IGF-1 gene expression was increased (p < 0.05) with a concomitant increase (p < 0.05) in IGF-1R protein expression. Mn also increased (p < 0.01) COX-2 gene expression. At 29 days, the upregulation of IGF-1 (p < 0.05) and COX-2 (p < 0.05) continued in the MBH. At this time, we observed increased (p < 0.05) LHRH gene expression in the POA/AVPV. Additionally, Mn stimulated prostaglandin E(2) and LHRH release from 29-day-old median eminences incubated in vitro. These results demonstrate that Mn, through the upregulation of IGF-1 and COX-2, may promote maturational events and glial-neuronal communications facilitating the increased neurosecretory activity, including that of LHRH, resulting in precocious pubertal development.

Anatomy of female puberty: The clinical relevance of developmental changes in the reproductive system.

PubMed

Colvin, Caroline Wingo; Abdullatif, Hussein

2013-01-01

Puberty is the period of biologic transition from childhood to adulthood. The changes that occur at this time are related to the increasing concentrations of sex steroid hormones. In females, most pubertal changes are caused by estrogen stimulation that results from the onset of central puberty. Significant development occurs in the organs of the female reproductive system and results in anatomic changes that characterize reproductive maturity. Adrenal and ovarian androgens also increase during puberty, affecting change that includes the promotion of certain secondary sex characteristics. The ability to recognize normal pubertal anatomy and distinguish between estrogen and androgen effects is important in the ability to diagnose and treat disorders of sex development, precocious puberty, pubertal delay, and menstrual irregularities in children and adolescents. An understanding of this developmental process can also help clinicians identify and treat reproductive pathology in adults and across all female life stages. Copyright © 2012 Wiley-Liss, Inc.

Adolescent THC exposure does not sensitize conditioned place preferences to subthreshold d-amphetamine in male and female rats.

PubMed

Keeley, Robin J; Bye, Cameron; Trow, Jan; McDonald, Robert J

2018-01-01

The acute effects of marijuana consumption on brain physiology and behaviour are well documented, but the long-term effects of its chronic use are less well known. Chronic marijuana use during adolescence is of increased interest, given that the majority of individuals first use marijuana during this developmental stage , and  adolescent marijuana use is thought to increase the susceptibility to abusing other drugs when exposed later in life. It is possible that marijuana use during critical periods in adolescence could lead to increased sensitivity to other drugs of abuse later on. To test this, we chronically administered ∆ 9 -tetrahydrocannabinol (THC) to male and female Long-Evans (LER) and Wistar (WR) rats directly after puberty onset. Rats matured to postnatal day 90 before being exposed to a conditioned place preference task (CPP). A subthreshold dose of d-amphetamine, found not to induce place preference in drug naïve rats, was used as the unconditioned stimulus. The effect of d-amphetamine on neural activity was inferred by quantifying cfos expression in the nucleus accumbens and dorsal hippocampus following CPP training. Chronic exposure to THC post-puberty had no potentiating effect on a subthreshold dose of d-amphetamine to induce CPP. No differences in cfos expression were observed. These results show that chronic exposure to THC during puberty did not increase sensitivity to d-amphetamine in adult LER and WR rats. This supports the concept that THC may not sensitize the response to all drugs of abuse.

MAMMARY GLAND DEVELOPMENT: EARLY LIFE EFFECTS FROM THE ENVIRONMENT

EPA Science Inventory

Mammary Gland Development: Early Life Effects from the Environment

S.E. Fenton. Reproductive Toxicology Division, National Health and Environmental Effects Laboratory, ORD, U.S. EPA, Research Triangle Park, NC 27711.

As signs of precocious puberty in girls reach ...

[Update on pubertal development among primary school students in Shanghai, 2014].

PubMed

Chen, Y; Zhang, Y T; Chen, C; Jiang, Y R; Song, Y J; Liu, S J; Jiang, F

2016-11-06

Objective: To investigate the current prevalence of pubertal development in healthy Shanghai schoolchildren. Methods: This study was a cross-sectional investigation focused on current pubertal development conducted in healthy Shanghai schoolchildren by multi-stage cluster sampling. The sample included 17 571 children in grades 1-5 investigated in June 2014. The data were weighted by inverse probability weighting (IPW) to make them more representative. At examination, stages of breast and pubic hair development were rated according to the Tanner method. Testicular volume was determined. Data on menarche and spermatorrhea were collected by the status quo method. The rates of precocious puberty, breast, and pubic hair development of Tanner stage ≥Ⅱ in girls aged 6-7 years, menarche in girls aged 6-9 years, and testicular volume ≥4 ml and pubic hair development of Tanner stage ≥Ⅱ in boys aged 6-8 years were calculated. All the data were weighted by IPW. Results: After data processing, 16 197 children's data were analyzed. In girls aged 6-7 years, 17.2% and 2.5% showed evidence of breast and pubic hair development at Tanner stage ≥Ⅱ, respectively. In girls aged 6-9 years, 0.3% had experienced menarche. Schoolgirls' rate of menarche was 4.7%. In girls aged 6-7 years, 19.0% were diagnosed with precocious puberty according to the classic criteria. In boys aged 6-8 years, 1.7% had testicular volume ≥4 ml, and 0.6% showed evidence of pubic hair development at Tanner stage ≥Ⅱ. Schoolboys' incidence rate of spermatorrhea was 0.1%. In boys aged 6-8 years, 2.3% were diagnosed with precocious puberty according to the classic criteria. All the numbers above were weighted. Conclusion: Proper education on adolescence and sex is essential for Shanghai schoolchildren.

Endocrine Disorders in Childhood: A Selective Survey of Intellectual and Educational Sequelae.

ERIC Educational Resources Information Center

Sandberg, David E.; Barrick, Christopher

1995-01-01

Examines intellectual and educational sequelae of selected endocrine systems and the psychosocial impact of their medical conditions. Many conditions are named including: Growth Hormone Deficiency, Turner Syndrome, Precocious Puberty, Klinefelters Syndrome, Congenital Hypothyroidism, and Insulin-Dependent Diabetes Mellitus. Gives psychoeducational…

Precocious puberty secondary to topical testosterone exposure.

PubMed

Franklin, Sherry Lynn; Geffner, Mitchell E

2003-01-01

We report a case of pronounced virilization, including marked penile and pubic hair growth, accelerated height velocity and skeletal maturation, and increased muscle mass in a 2.67 year-old boy resulting from presumed inadvertent, long-term exposure to a topical testosterone cream being used by his father.

Circulating MKRN3 Levels Decline During Puberty in Healthy Boys.

PubMed

Busch, Alexander S; Hagen, Casper P; Almstrup, Kristian; Juul, Anders

2016-06-01

Initiation and progression of puberty requires concerted action of hypothalamic activating and inhibiting factors. Recently, cases of familial central precocious puberty have been linked to loss-of-function mutations of makorin RING-finger protein 3 (MKRN3) indicating a pivotal inhibitory role of the protein on GnRH secretion. To investigate peripubertal circulating MKRN3 levels in healthy boys. Population-based longitudinal study in healthy Danish boys. General community. Healthy boys (n = 60) aged (median [range]) 9.3 (5.8-11.8) years at baseline followed for 6.0 (0.5-7.6) years (2006-2014) with blood sampling every 6 months. None. Serum levels of MKRN3: 623 samples, median (range) 12 (2-14) per boy. MKRN3 levels declined before onset of puberty; the geometric mean (95% confidence interval) 5 years before onset of puberty vs last visit before onset of puberty was 216 (169-272) pg/mL vs 128 (118-139) pg/mL (P < .001), respectively. MKRN3 levels continued to decrease as puberty progressed. MKRN3 levels were not associated with age at onset of puberty. Declining MKRN3 before pubertal onset support MKRN3 as an inhibitor of GnRH secretion during midchildhood.

Hypothalamic hamartoma with precocious puberty: a case report.

PubMed

Amin, M S; Kader, M A; Huq, F I; Khan, N A

2012-07-01

Hypothalamic hamartoma (HH) is one of the most important causes of central precocious puberty in male children. Hamartomas are malformations composed of ectopic gonadotropic hormone (GnRH) neurons which secrete pulsatile gonadotropin releasing hormone. They are generally observed in children under 3 years. A case of 11/3 year-old male child presented with premature development of secondary sexual characters i.e., growth of pubic and axillary hair, enlargement of penis and acne over the face for the last 5 months. On physical examination, his height was 1.02 m and his weight 18kg, enlarged penile length of which 58mm; testicles were enlarged in size right one measuring 32X25mm and the left 30X23mm. His hematological and other biochemical investigations revealed no abnormality. Plain radiographic examination revealed radiological bone age of about 8-9 years. Endocrinological findings were as follows: Follicle stimulating hormone (FSH): 1.5mIU/ml, Luteinizing hormone (LH): 9.1mIU/ml, Testosterone: 701ng/dl (Testosterone level less than 30ng/dl in prepubertal age). Thyroid function tests were normal. Patient showed no adrenal pathology on ultrasound and his testicular parenchyma was homogeneous echotexture with the size of 30X22X16mm on the right (volume 5.4ml) and 30X20X15mm on the left (volume 4.6ml). With above physical & endocrinological findings and age of the child, it was suspected as a case of central precocious puberty. Subsequently MR imaging of the brain done & showed an oval non-enhancing pedunculated hypothalamic mass arising from the tubercinereum that was iso to hypointense to brain parenchyma on T1 - and intermediate signal on T2-weighted images, 20X10X10mm in diameter, extending into suprasellar cistern. During follow up after 06 months of starting conservative medication with gonadotropin-releasing hormone (GnRH) analog (Leuprolide acetate), his progression of puberty has been arrested and the testosterone level 18ng/dl, which is normal for his age.

The timing of normal puberty and the age limits of sexual precocity: variations around the world, secular trends, and changes after migration.

PubMed

Parent, Anne-Simone; Teilmann, Grete; Juul, Anders; Skakkebaek, Niels E; Toppari, Jorma; Bourguignon, Jean-Pierre

2003-10-01

During the past decade, possible advancement in timing of puberty has been reported in the United States. In addition, early pubertal development and an increased incidence of sexual precocity have been noticed in children, primarily girls, migrating for foreign adoption in several Western European countries. These observations are raising the issues of current differences and secular trends in timing of puberty in relation to ethnic, geographical, and socioeconomic background. None of these factors provide an unequivocal explanation for the earlier onset of puberty seen in the United States. In the formerly deprived migrating children, refeeding and catch-up growth may prime maturation. However, precocious puberty is seen also in some nondeprived migrating children. Attention has been paid to the changing milieu after migration, and recently, the possible role of endocrine- disrupting chemicals from the environment has been considered. These observations urge further study of the onset of puberty as a possible sensitive and early marker of the interactions between environmental conditions and genetic susceptibility that can influence physiological and pathological processes.

Precocious Puberty in Adolescent Girls: A Biomarker of Later Psychosocial Adjustment Problems

ERIC Educational Resources Information Center

Tremblay, Line; Frigon, Jean-Yves

2005-01-01

We have investigated the hypothesis that stress condition will accelerate pubertal maturation in adolescent girls and that faster maturing girls will display more behavioral problems than their on-time or late-maturing peers during pubertal development. Longitudinal data were collected yearly from 1986 to 1997. Parents of 1039 French-speaking…

Antral follicular count is a tool that allows the selection of more precocious animals at weaning

USDA-ARS?s Scientific Manuscript database

Lifetime productivity and longevity are greater in those beef cows that give birth early in their first calving season. This is why age at puberty and first calving affect the reproductive performance of breeding cows during the remainder of their productive life. Recent evidence suggests that antra...

Study of the family of a patient with male-limited precocious puberty (MPP) due to T1193C transition in exon 11 of LH receptor gene.

PubMed

Ignacak, M; Starzyk, J; Dziatkowiak, H; Trzeciak, W H

2002-03-01

Molecular diagnostics of the LHR gene was conducted in a 5-year-old boy with clinical symptoms and hormonal profile typical of precocious puberty. His parents and 4 sisters were also diagnosed. Single-strand conformation polymorphism analysis under temperature gradient conditions (Multitemperature SSCP) of 3 overlapping fragments of exon 11 of LHR gene revealed a mutation in the fragment spanning nucleotides 1072 to 1804. This mutation was found in the patient, in his mother and in his 4 sisters, and was confirmed by digestion with the use of restriction enzyme Bbr Cl. Direct sequencing revealed a heterozygous T1193C transition in the DNA fragment of the patient and in one of the alleles of his mother's and sister's DNA. This mutation causes Met398Thr substitution in the second transmembrane helix and results in a constitutive activation of LH receptor. This is the second identical mutation detected in Poland and one of the 7 identified so far in the world population.

McCune-Albright syndrome: growth hormone and prolactin hypersecretion.

PubMed

Christoforidis, Athanasios; Maniadaki, Ilianna; Stanhope, Richard

2006-05-01

McCune-Albright syndrome (MAS) has a special interest for endocrinologists as its pathogenesis results in hypersecretion of hormones in peripheral endocrine tissues. This can be expressed as precocious puberty, mainly in girls, primary hyperthyroidism, growth hormone (GH) and/or prolactin excess, hyperparathyroidism and hypercortisolism. The incidence of GH excess among patients with MAS has been assessed as up to 21%. The pathogenesis of GH hypersecretion in MAS is not completely understood, whereas it seems to be different from the aetiology of acromegaly/gigantism in non-MAS patients. The clinical expression of GH excess can be masked because of precocious puberty or craniofacial fibrous dysplasia, indicating the necessity for screening. Medical treatment is usually the only option in MAS patients with GH excess, as transsphenoidal surgery is usually restricted due to massive thickening of the skull base, whereas radiotherapy is contraindicated due to probable higher predisposition to sarcomatous transformation. The use of bromocriptine, cabergoline and octreotide, or the combination of these, has shown variable results, whereas pegvisomant, a GH receptor antagonist, is a new promising option, although not yet used in patients with MAS.

Combined adrenal failure and testicular adrenal rest tumor in a patient with nicotinamide nucleotide transhydrogenase deficiency.

PubMed

Hershkovitz, Eli; Arafat, Maram; Loewenthal, Neta; Haim, Alon; Parvari, Ruti

2015-09-01

The nicotinamide nucleotide transhydrogenase (NNT) enzyme is the main generator of nicotinamide adenine dinucleotide phosphate-oxidase in the mitochondrion. Mutations of the NNT gene have been recently implicated in familial glucocorticoid deficiency. We describe the long-term clinical course of a NNT-deficient 20-year-old patient with combined adrenal failure who had developed a testicular adrenal rest tumor and precocious puberty. The patient's medical records were reviewed. Whole-exome sequencing was performed on DNA obtained from the patient and family members. The patient experienced Addisonian crisis at 10 months of age. Enlarged testicular volume and precocious puberty, accompanied by increased testosterone levels, were noted at 6 years. Testicular biopsy revealed a adrenal rest tumor, which regressed after intensification of glucocorticoid treatment. Genetic studies disclosed a c.1163A>C, p.Tyr388Ser substitution on the NNT gene. This mutation is predicted to be damaging to NNT function. We demonstrated for the first time that the clinical spectrum of NNT deficiency may consist of mineralocorticoid deficiency and testicular involvement as well.

Gigantism treated by pure endoscopic endonasal approach in a case of McCune-Albright syndrome with sphenoid fibrous dysplasia: a case report.

PubMed

Sharifi, Guive; Jalessi, Maryam; Sarvghadi, Farzaneh; Farhadi, Mohammad

2013-12-01

McCune-Albright syndrome (MAS) is an uncommon polyostotic manifestation of fibrous dysplasia in association with at least one endocrinopathy that is mostly associated with precocious puberty and hyperpigmented skin macules named café-au-lait spots. We present an atypical manifestation of McCune-Albright syndrome in a 19-year-old man with the uncommon association of polyostotic fibrous dysplasia and gigantism in the absence of café-au-lait spots and precocious puberty. He presented with a height increase to 202 cm in the previous 3 years, which had become more progressive in the few months prior. Physical examination revealed only a mild facial asymmetry; however, a computed tomography (CT) scan discovered vast areas of voluminous bones with ground-glass density and thickening involving the craniofacial bones and skull base. Magnetic resonance imaging (MRI) found a right stalk shift of the pituitary with a 20 mm pituitary adenoma. We describe the diagnostic and endoscopic endonasal transsphenoidal approach for excision of the tumor. Georg Thieme Verlag KG Stuttgart · New York.

[The establishment of environmental endocrine disruptors induced precocious puberty Macaca fascicularis model and the intervention of yin nourishing fire purging Chinese materia medica].

PubMed

Zhu, Lin; Cai, De-pei

2012-12-01

To establish the environmental endocrine disruptors (EEDs) induced precocious puberty macaca fascicularis model, thus verifying the antagonism of yin nourishing fire purging Chinese materia medica (YNFPCMM) against the estrogenic effects. (1) The female prepubescent monkeys at different months old were fed with high dose and low dose EEDs. By observing EEDs' estrogenic effects, the optimal age, the optimal exposure dose, and the optimal exposure time were determined. (2) Fifteen female prepubescent monkeys were randomly divided into the exposure group, the treatment group, and the control group, 5 in each group. Those in the exposure group were fed with EEDs such as nonylphenol (4-NP) and bisphenol A (BPA). Those in the treatment group were fed with EEDs and YNFPCMM. Those in the control group were fed with dissolvent such as corn oil. The therapeutic course was 4 weeks. By the end of the treatment, the serum estrogen level was measured and the maturation index of the vaginal keratinocytes was calculated. The uterus was extracted to measure the wet weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height. (1) Twenty month was the optimal exposure age. The low dose EEDs was the best exposure dose, and 4 weeks was the optimal exposure time. (2) Compared with the control group, the serum estrogen level obviously increased, the maturation index of the vaginal keratinocytes significantly increased, the wet uterus weight, the endometrial thickness, the ring-shaped myometrium thickness, the endometrial epithelial cells, and the glandular epithelium height significantly increased in the exposure group (P<0.05). Compared with the exposure group, the aforesaid indices significantly decreased in the treatment group (P<0.05). The EEDs induced precocious puberty macaca fascicularis model was successfully established in this study. The EEDs were proved to have estrogenic-like activities. YNFPC-MM was proved to have significant antagonism like estrogenic activities.

Insulin resistance, obesity, hypofibrinolysis, hyperandrogenism, and coronary heart disease risk factors in 25 pre-perimenarchal girls age < or =14 years, 13 with precocious puberty, 23 with a first-degree relative with polycystic ovary syndrome.

PubMed

Glueck, Charles J; Morrison, John A; Wang, Ping

2008-10-01

Pre-peri-menarchal diagnosis of polycystic ovary syndrome (PCOS) is important, because intervention with metformin-diet may prevent progression to full blown PCOS. In 25 girls age < or =14 years with probable familial PCOS, 10 pre-, 15 post-menarchal, 13 with precocious puberty, 23 with a first-degree relative with PCOS, we hypothesized that reversible coronary heart disease (CHD) risk factors, insulin resistance, clinical and biochemical hyperandrogenism, and hypofibrinolysis were already established. Fasting measures: insulin, glucose, total, LDL- (LDL-C), and HDL-cholesterol (HDL-C), triglycerides (TG), systolic and diastolic blood pressure (SBP, DBP), plasminogen activator inhibitor activity (PAI-Fx), total (T) and free testosterone (FT), androstenedione, and DHEAS. Clinical and/or biochemical hyperandrogenism was present in all 25 girls, with elevations of T or FT, or androstenedione in seven of ten pre-menarchal girls and in all 15 post-menarche. PAI-Fx was high in 28% of the 25 girls vs 6.5% in age-gender-race matched controls (p = 0.013). Categorized by race-age-specific distributions in 870 schoolgirls, the 25 girls with probable familial PCOS were more likely to have top decile body mass index (BMI), insulin, HOMA-insulin resistance (HOMA-IR), SBP, DBP, and TG, and bottom decile HDL-C. By analysis of variance, adjusting for race, age and BMI, PCOS girls had higher FT and waist circumference than controls, but did not differ for SBP, DBP, HDL-C, or TG (p>0.05). Pre-peri-menarchal acquisition of centripetal obesity amplifies CHD risk factors and hypofibrinolysis in hyperandrogenemic girls with probable familial PCOS and precocious puberty. When schoolgirls become as obese as girls with probable familial PCOS, they acquire the same CHD risk factors, and differ only by lower free T and less centripetal obesity.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice

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

Wang, Yongan

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposuremore » levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2 mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2 mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. - Highlights: • Maternal exposure to di (2-ethylhexyl) phthalate disturbs fetus sex determination. • DEHP upregulated Foxl2 expression potentially disturbs postnatal granulosa cell differentiation. • DEHP accelerated medulla follicular atresia potentially leading to precocious puberty.« less

Increase in endogenous estradiol in the progeny of obese rats is associated with precocious puberty and altered follicular development in adulthood.

PubMed

Ambrosetti, Valery; Guerra, Marcelo; Ramírez, Luisa A; Reyes, Aldo; Álvarez, Daniela; Olguín, Sofía; González-Mañan, Daniel; Fernandois, Daniela; Sotomayor-Zárate, Ramón; Cruz, Gonzalo

2016-07-01

Maternal obesity during pregnancy has been related with several pathological states in offspring. However, the impact of maternal obesity on reproductive system on the progeny is beginning to be elucidated. In this work, we characterize the effect of maternal obesity on puberty onset and follicular development in adult offspring in rats. We also propose that alterations in ovarian physiology observed in offspring of obese mothers are due to increased levels of estradiol during early development. Offspring of control dams and offspring of dams exposed to a high-fat diet (HF) were studied at postnatal days (PND) 1, 7, 14, 30, 60, and 120. Body weight and onset of puberty were measured. Counting of ovarian follicles was performed at PND 60 and 120. Serum estradiol, estriol, androstenedione, FSH, LH, and insulin levels were measured by ELISA. Hepatic CYP3A2 expression was determined by Western blot. HF rats had a higher weight than controls at all ages and they also had a precocious puberty. Estradiol levels were increased while CYP3A2 expression was reduced from PND 1 until PND 60 in HF rats compared to controls. Estriol was decreased at PND60 in HF rats. Ovaries from HF rats had a decrease in antral follicles at PND60 and PND120 and an increase in follicular cysts at PND60 and PND120. In this work, we demonstrated that maternal obesity in rats alters follicular development and induces follicular cysts generation in the adult offspring. We observed that maternal obesity produces an endocrine disruption through increasing endogenous estradiol in early life. A programmed failure in hepatic metabolism of estradiol is probably the cause of its increase.

[Analysis of a family affected with familial male-limited precocious puberty due to a Ala568Val mutation in LHCGR gene].

PubMed

Chen, Rui-min; Zhang, Ying; Yang, Xiao-hong; Lin, Xiang-quan

2012-12-01

Familial male-limited precocious puberty (FMPP) is due to constitutive activation of a mutant luteinizing hormone/choriogonadotropin receptor (LH/CGR) leading to elevated testosterone synthesis in testicular Leydig cells. In the present study, we have analyzed the LHCGR gene for members of a Chinese FMPP family. Physical examinations have included assessment of penile length, testicular volume and pubic hair. Bone age assessment, levels of testosterone and gonadotropin-releasing hormone (GnRH) stimulations tests were measured. DNA was extracted from blood samples of the proband and his parents using an QIAGEN Blood DNA Mini Kit. The 11 exons of LHCGR gene were amplified using an AmpliTaq PCR system, and the PCR products were sequenced using an ABI3130xl Genetic Analyzer. The affected boy was 3 year and 1 month old and showed typical clinical manifestation of peripheral precocious puberty. His height was 116.8cm (+5.1s) and Tanner stages were PH 2. Testicular volume was 8 mL bilaterally, penile was 8.5 cm × 2.5 cm. Basal testosterone was 2310 ng/L and bone age was 9 years. GnRH stimulation test revealed a prepubertal response to gonadotropin. The peak of LH was 2.66 IU/L, and the peak of FSH was 1.03 IU/L. Upon sequencing exon 11 of the LHCGR, a heterozygous point mutation of nucleotide 1703 from C to T was detected, which resulted in an amino acid transition from Ala (GCC) to Val (GTC) at position 568. Thus the mutation of LHCGR gene was confirmed to be constitutively active. After treating with aromatase inhibitors for half a year, the patient showed an increase in bone age and height by half a year and 4 cm, respectively. The same point mutation was detected in the patient's father, but did not have any influence on his puberty development. A novel point mutation of the LHCGR gene has been identified in a family affected with FMPP. The c.1703C>T mutant LHCGR was confirmed to be constitutively active, which has led to maturation and proliferation of Leydig cells. The variable phenotype within the family suggested variable expressivity of the disease.

Effects of Stress After Hurricanes Katrina and Rita on Pubertal Disorders in Children

PubMed Central

Ponnapakkam, Adharsh; Gensure, Robert

2008-01-01

Hurricanes Katrina and Rita caused widespread damage that resulted in increased stress levels for families living in the New Orleans area. This study examined the relationship between this stress and the onset of puberty in children by conducting a retrospective chart review of patients referred before and after the storm to a pediatric endocrine practice in New Orleans. The total number of new patients referred and the incidence of diagnoses that are unlikely to be affected by stress (ie, thyroid disease and premature adrenarche) were essentially unchanged. On the other hand, the incidence of central precocious puberty decreased by 52% after the storm, while the incidence of pubertal delay increased by 9% in the post storm period. This study thus provides evidence that stress delays the onset of puberty in children. PMID:21603464

Combination growth hormone and gonadotropin releasing hormone analog therapy in 11beta-hydroxylase deficiency.

PubMed

Bajpai, Anurag; Kabra, Madhulika; Menon, P S N

2006-06-01

Diagnosis of 11beta-hydroxylase deficiency was made in a boy at the age of 2 1/2 years on the basis of peripheral precocious puberty, growth acceleration (height standard deviation score +4.4) with advanced skeletal maturation (bone age 8.4 years) and elevated deoxycortisol levels. Glucocorticoid supplementation led to normalization of blood pressure but was associated with progression to central precocious puberty and increase in bone age resulting in decrease in predicted adult height to 133.7 cm (target height 163 cm). The child was started on GnRH analog (triptorelin 3.75 mg every 28 days), which led to improvement in predicted adult height by 3.1 cm over 15 months. Addition of growth hormone (0.1 IU/kg/day) resulted in improvement in predicted adult height (151 cm) and height deficit (12 cm) over the next 3.6 years. Final height (151 cm) exceeded predicted height at the initiation of GnRH analog treatment by 17.3 cm. This report suggests that combination GH and GnRH analog treatment may be useful in improving height outcome in children with 11beta-hydroxylase deficiency and compromised final height.

Pamidronic acid and cabergoline as effective long-term therapy in a 12-year-old girl with extended facial polyostotic fibrous dysplasia, prolactinoma and acromegaly in McCune-Albright syndrome: a case report

PubMed Central

2012-01-01

Introduction McCune-Albright syndrome is a complex inborn disorder due to early embryonal postzygotic somatic activating mutations in the GNAS1 gene. The phenotype is very heterogeneous and includes polyostotic fibrous dysplasia, typically involving the facial skull, numerous café-au-lait spots and autonomous hyperfunctions of several endocrine systems, leading to hyperthyroidism, hypercortisolism, precocious puberty and acromegaly. Case presentation Here, we describe a 12-year-old Caucasian girl with severe facial involvement of fibrous dysplasia, along with massive acromegaly due to growth hormone excess and precocious puberty, with a prolactinoma. Our patient was treated with a bisphosphonate and the prolactin antagonist, cabergoline, resulting in the inhibition of fibrous dysplasia and involution of both the prolactinoma and growth hormone excess. During a follow-up of more than two years, no severe side effects were noted. Conclusion Treatment with bisphosphonates in combination with cabergoline is a suitable option in patients with McCune-Albright syndrome, especially in order to circumvent surgical interventions in patients suffering from polyostotic fibrous dysplasia involving the skull base. PMID:22273876

Pubertal development of the first cohort of young adults conceived by in-vitro fertilization in the United States

PubMed Central

Beydoun, Hind A.; Sicignano, Nicholas; Beydoun, May; Bocca, Silvina; Stadtmauer, Laurel; Oehninger, Sergio

2010-01-01

Objective To characterize pubertal development of the first generation of young adults born as a result of in-vitro fertilization (IVF). Demographic, clinical and body size characteristics were examined in relation to developmental milestones. Design Cross-sectional. Setting Academic center. Patients Young adults (18–26 years) conceived by IVF (no gamete/embryo manipulation), 1981–1990. Intervention Self-administered questionnaire. Main outcome measures Age at puberty onset, body size. Results Of 560 eligible young adults, 173 completed the survey (response rate=30.9%). We analyzed data on 166 respondents, 71 males and 95 females. No cases of delayed or precocious puberty were observed in the study sample. As expected, age at puberty onset was significantly higher (P < 0.0001) among males (12.3 years) compared to females (11.5 years). A few developmental milestones were predicted by maternal age and infertility diagnoses. For both genders, a direct association was noted between age at puberty onset and height achieved in young adulthood. Structural equations models suggested an inverse relationship of female gender with age at puberty onset and body mass index. Conclusions IVF-conceived young adults did not exhibit pubertal abnormalities. Female gender and age at puberty onset independently predicted body mass index of IVF offspring in young adulthood. PMID:20547390

Permanent hypopituitarism is rare after structural traumatic brain injury in early childhood.

PubMed

Heather, Natasha L; Jefferies, Craig; Hofman, Paul L; Derraik, José G B; Brennan, Christine; Kelly, Patrick; Hamill, James K M; Jones, Rhys G; Rowe, Deborah L; Cutfield, Wayne S

2012-02-01

We sought to determine the incidence of permanent hypopituitarism in a potentially high-risk group: young children after structural traumatic brain injury (TBI). We conducted a cross-sectional study with longitudinal follow-up. Dynamic tests of pituitary function (GH and ACTH) were performed in all subjects and potential abnormalities critically evaluated. Puberty was clinically staged; baseline thyroid function, prolactin, IGF-I, serum sodium, and osmolality were compared with age-matched data. Diagnosis of GH deficiency was based on an integrated assessment of stimulated GH peak (<5 μg/liter suggestive of deficiency), IGF-I, and growth pattern. ACTH deficiency was diagnosed based on a subnormal response to two serial Synacthen tests (peak cortisol <500 nmol/liter) and a metyrapone test. We studied 198 survivors of structural TBI sustained in early childhood (112 male, age at injury 1.7 ± 1.5 yr) 6.5 ± 3.2 yr after injury. Sixty-four of the injuries (33%) were inflicted and 134 (68%) accidental. Two participants had developed precocious puberty, which is within the expected background population rate. Peak stimulated GH was subnormal in 16 participants (8%), in the context of normal IGF-I and normal growth. Stimulated peak cortisol was low in 17 (8%), but all had normal ACTH function on follow-up. One participant had a transient low serum T(4). Therefore, no cases of hypopituitarism were recorded. Permanent hypopituitarism is rare after both inflicted and accidental structural TBI in early childhood. Precocious puberty was the only pituitary hormone abnormality found, but the prevalence did not exceed that of the normal population.

A case of an adoptive girl with precocious puberty: the problem of age estimation.

PubMed

De Donno, Antonio; Roca, Roberta; Introna, Francesco; Santoro, Valeria

2013-09-10

Age estimation is one of the main tasks of forensic anthropology and odontology, both on the dead and the living. In living subjects, age estimation may be used to establish an individual's status as a minor in cases involving adoption, criminal responsibility, child pornography, and those seeking asylum, especially where adequate identification documents are lacking. The authors report a case about age assessment of a girl born in Mbujimayi (Democratic Republic of Congo) and later adopted in Italy. The birth certificate issued after finding the child in a state of abandonment (in December 2007), bore date of 12.12.2004, but this was in contrast with the year of birth - 2003 - stated on the certification available to the center that had provided accommodation to the girl in Africa. Her adoptive parents reported that the child had been diagnosed with precocious puberty and was thus under treatment. She weighed 32.5 kg and was 132.5 cm tall. Body mass index (BMI) corresponded to the range between 9.5 and 14 years of age. The assessment of maturity indicators (sexual characteristics) placed the child at the lower limits of Stage II of Tanner's classification (sparse growth of long, slightly darkened, downy straight pubic hair; elevation of the breast and nipple as a small mound with increased diameter of the areolae). The skeletal age was determined by taking X-rays of the hand and wrist using Fels, TW2 and Greulich and Pyle methods. Dental growth was assessed through orthopantomogram using Demirjian's technique. The methods applied were adjusted considering the studies on African population found in the literature, and a skeletal and dental age of 10 years was established. Afterwards, the wrist X-rays performed at the Children's Hospital of Bari, 7 months before our investigation, revealed a skeletal age of 7 years. This evidence showed that, despite the treatment the child had promptly initiated, early puberty had influenced the skeletal growth with an acceleration of about 2 years. Therefore, the age we detected (10 years) was the result of precocious puberty. Then, we backdated the girl's birth (by about 2 years, based on current studies), stating that she was about 8 at the time of our investigation. This case is significant both for the racial differences that need to be considered in age assessment, and for the importance of any pathology (growth disorders) that may affect physiological development and make the applied methods poorly reliable. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

[Deviation in psychosexual development in the pre-puberty children].

PubMed

Liavshina, G Kh

2002-01-01

Psychosexual health of 308 children, aged 2-11 years, as well as that of their families, was studied. Deviations in psychosexual development were found in 34.6% of the children examined. The following types were detected: difficulties in formation of gender-determined behavior features--64.4%, precocious psychosexual development--13.7%, delayed psychosexual development--12.3%, obsessive masturbation--9.6%. Risk factors for deviant psychosexual development were found.

Adult height in patients with familial male-limited precocious puberty and the role of an aromatase inhibitor in patient management.

PubMed

Lane, Laura C; Flowers, Josephine; Johnstone, Helen; Cheetham, Tim

2018-04-25

There is little adult height data in patients with familial male-limited precocious puberty (FMPP) and no management consensus. We assessed the treatment and adult height in local patients with FMPP and those reported in the literature. Growth data were obtained on four local patients with FMPP and a search performed to obtain management details and adult height data on cases in the literature. UK (90) population standards were used to calculate standard deviation scores (SDS). Adult height data were available on 25 men with FMPP of whom 21 were treated. Median adult height SDS of patients was -1.5 SD with a mid-parental target of -0.6 SD (p=0.1). Eight patients (32%) had an adult height above the mid-parental target and seven patients (28%) had a height >2 SD below the mean. The median height SD was -0.03 in untreated patients and +0.5 SD in those receiving an aromatase inhibitor. There was no relationship between height and age at presentation. Aromatase inhibitor therapy is associated with a positive height outcome in FMPP but the outcome with and without intervention is unpredictable. Clinicians need to be cautious when counselling families about the potential height outcome in FMPP.

[Age of onset of puberty in Chilean boys according to testicular volume and Tanner stage].

PubMed

Gaete, Ximena; García, Roberto; Riquelme, Joel; Codner, Ethel

2015-03-01

A secular trend towards a younger age of puberty onset has been reported in Chilean girls. To evaluate the age of onset of puberty and prevalence of early puberty in Chilean boys. A pediatric endocrinologist examined 319 children attending schools in central Santiago. Pubertal development was assessed by testicular volume (TV) and genital inspection (GI) using Tanner graduation. Precocious and early puberty development was diagnosed if TV ≥ 4 ml or GI > stage 2 occurred in boys younger than 9 years and at 9-10 years of age, respectively. Pubertal onset occurred at 10.2 ± 1.5 years according to TV and at 11.1 ± 1.6 years according to GI (p < 0.01). Before the age of nine, 15.2% of children had a VT ≥ 4 ml, 3% had genital changes in GI and only 3% had both changes simultaneously. Early puberty was observed in 23.8% of children according to TV and 9.5% according to GI. However, no child of less than 11 years old had a TV ≥ 4 ml, genital changes and pubic hair simultaneously. Late pubertal stages occurred at the same age according to both criteria used. Body mass index z score was not associated with the age of pubertal onset. Testicular enlargement occurs one year earlier than changes in genitalia according to inspection. Testicular growth, but not late stages of puberty, are occurring one year earlier than previously reported in Chile 10 years ago.

Evaluation and Referral of Children With Signs of Early Puberty.

PubMed

Kaplowitz, Paul; Bloch, Clifford

2016-01-01

Concerns about possible early pubertal development are a common cause for referral to pediatric medical subspecialists. Several recent studies have suggested that onset of breast and/or pubic hair development may be occurring earlier than in the past. Although there is a chance of finding pathology in girls with signs of puberty before 8 years of age and in boys before 9 years of age, the vast majority of these children with signs of apparent puberty have variations of normal growth and physical development and do not require laboratory testing, bone age radiographs, or intervention. The most common of these signs of early puberty are premature adrenarche (early onset of pubic hair and/or body odor), premature thelarche (nonprogressive breast development, usually occurring before 2 years of age), and lipomastia, in which girls have apparent breast development which, on careful palpation, is determined to be adipose tissue. Indicators that the signs of sexual maturation may represent true, central precocious puberty include progressive breast development over a 4- to 6-month period of observation or progressive penis and testicular enlargement, especially if accompanied by rapid linear growth. Children exhibiting these true indicators of early puberty need prompt evaluation by the appropriate pediatric medical subspecialist. Therapy with a gonadotropin-releasing hormone agonist may be indicated, as discussed in this report. Copyright © 2016 by the American Academy of Pediatrics.

Imaging of pediatric pituitary endocrinopathies

PubMed Central

Chaudhary, Vikas; Bano, Shahina

2012-01-01

Accurate investigation of the hypothalamic-pituitary area is required in pediatric patients for diagnosis of endocrine-related disorders. These disorders include hypopituitarism, growth failure, diencephalic syndrome, delayed puberty, precocious puberty, diabetes insipidus, syndrome of inappropriate antidiuretic hormone (SIADH) secretion, and hyperpituitarism. Magnetic resonance imaging (MRI) is the modality of choice to visualize hypothalamic-pituitary axis and associated endocrinopathies. Neuroimaging can be normal or disclose abnormalities related to pituitary-hypothalamic axis like (i) congenital and developmental malformations; (ii) tumors; (iii) cystic lesions; and (iv) infectious and inflammatory conditions. Classical midline anomalies like septo-optic dysplasias or corpus callosum agenesis are commonly associated with pituitary endocrinopathies and also need careful evaluation. In this radiological review, we will discuss neuroendocrine disorders related to hypothalamic pituitary-axis. PMID:23087850

Successful desensitization to Gonadotropin-releasing hormone analogue Triptorelin Acetate using a sustained-release depot preparation.

PubMed

Chan Ng, Pauline; Huang, Chiung-Hui; Rajakulendran, Mohana; Tan, Michelle Meiling; Wang, Ping Ping; Tay, Lei Qiu; Goh, Siok Ying; Shek, Lynette Pei-Chi; Tham, Elizabeth Huiwen

2018-05-29

Gonadotropin-releasing hormone (GnRH) analogues are commonly used in pediatric patients in the treatment of central precocious puberty 1 . GnRH analogues suppress the secretion of gonadotropins and sex hormones, preventing progression to advanced puberty and reduced final adult height secondary to accelerated fusion of growth plates. GnRH analogues are also used in adults for treatment of endometriosis 2 and prostatic cancer 3 . Hypersensitivity reactions to GnRH analogues are exceedingly rare 4-6 and to date, we are unaware of any desensitization protocols for GnRH hypersensitivity in the literature or used in clinical practice. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

[Clinical values of triptorelin stimulating test in assessing hypothalamus-pituitary-gonad axis function in male patients with hypothalamus-pituitary-gonad axis disorders].

PubMed

Wu, Xue-yan; Nie, Min; Lu, Shuang-yu; Mao, Jiang-feng

2011-03-15

To investigate the clinical values of luteinizing hormone-releasing hormone (LHRH) α (triptorelin) stimulating test in the differential diagnoses of hypothalamus-pituitary-gonad axis (HPGA) disorders. A total of 229 male patients with various HPGA disorders were recruited for triptorelin stimulating test. And all patients were followed up for 12 - 48 months until a definite diagnosis was made. The values of triptorelin stimulating test in the differential diagnoses of HPGA disorders were assessed by examining the close relationship between LHmax and the final clinical diagnosis. (1) LH levels rose steady after an intramuscular injection of triptorelin 100 µg and the time of LHmax appeared at 45 - 60 min. (2) LHmax < 4 U/L indicated the function of HPGA was not activated. LHmax in the range of 4 - 12 U/L indicated the patients might have constitutional delayed puberty development. LHmax > 12 U/L indicated the fulfilled puberty development. Triptorelin stimulating test can precisely evaluate the functions of HPGA in various HPGA disorders and provide valuable information for the differential diagnoses in constitutional delayed puberty development, hypogonadotropic hypogonadism, central and peripheral precocious puberty disorders.

Dopamine mediates testosterone-induced social reward in male Syrian hamsters.

PubMed

Bell, Margaret R; Sisk, Cheryl L

2013-03-01

Adolescent maturation of responses to social stimuli is essential for adult-typical sociosexual behavior. Naturally occurring developmental changes in male Syrian hamster responses to a salient social cue, female hamster vaginal secretions (VS), provide a good model system for investigating neuroendocrine mechanisms of adolescent change in social reward. Sexually naïve adult, but not juvenile, males show a conditioned place preference (CPP) to VS, indicating that VS is not rewarding before puberty. In this series of experiments, the authors examined the roles of testosterone and dopamine receptor activation in mediating the adolescent gain in positive valence of VS. Experiment 1 showed that testosterone replacement is necessary for gonadectomized adult hamsters to form a CPP to VS. Experiment 2 showed that testosterone treatment is sufficient for juvenile hamsters to form a CPP to VS, and that the dopamine receptor antagonist haloperidol blocks formation of a CPP to VS in these animals. Experiments 3 and 4 demonstrated that the disruption of VS CPP with low doses of haloperidol is the result of a reduction in the attractive properties of VS and not attributable to aversive properties of haloperidol. Together, these studies demonstrate that the unconditioned rewarding properties of a social cue necessary for successful adult sociosexual interactions come about as the result of the pubertal increase in circulating testosterone in male hamsters. Furthermore, this social reward can be prevented by dopamine receptor antagonism, indicating that hypothalamic and/or mesocorticolimbic dopaminergic circuits are targets for hormonal activation of social reward.

Triptorelin depot stimulation test for central precocious puberty.

PubMed

Strich, David; Kvatinsky, Noa; Hirsch, Harry J; Gillis, David

2013-01-01

Acute gonadotropin responses following depot leuprolide acetate injection are useful for monitoring therapeutic efficacy in central precocious puberty. Similar monitoring of therapy in patients treated with another widely used GnRH agonist, depot triptorelin, has not yet been reported. The objective of this study was to test the use of gonadotropin levels after therapeutic injections of depot triptorelin for evaluating efficacy of therapy. Thirty-two patients (29 girls and three boys) were treated with triptorelin depot, 3.75 mg per vial, between 2006 and 2010. Treatment was initiated at 8.27±1.76 years (range, 4.6-11.6 years). Blood was drawn before and at variable times between 30 min and 2 h after injections. Clinical tests were retrospectively collected. After the first injection, the 60-min mean luteinizing hormone (LH) level was 21.6.1±18.0 IU/L and the follicle-stimulating hormone (FSH) was 13.5±3.6 IU/L. After subsequent injections, for those who showed clinical suppression, the standard deviations above the mean were 3.6 IU/L for FSH and 2.1 IU/L for LH. The LH levels of two patients who did not suppress sufficiently were at these limits or higher. Sixty-minute postinjection depot triptorelin levels of LH can be successfully used to evaluate the efficacy of treatment with this agent. Limits for suppressed levels have been determined.

[Algorithms based on medico-administrative data in the field of endocrine, nutritional and metabolic diseases, especially diabetes].

PubMed

Fosse-Edorh, S; Rigou, A; Morin, S; Fezeu, L; Mandereau-Bruno, L; Fagot-Campagna, A

2017-10-01

Medico-administrative databases represent a very interesting source of information in the field of endocrine, nutritional and metabolic diseases. The objective of this article is to describe the early works of the Redsiam working group in this field. Algorithms developed in France in the field of diabetes, the treatment of dyslipidemia, precocious puberty, and bariatric surgery based on the National Inter-schema Information System on Health Insurance (SNIIRAM) data were identified and described. Three algorithms for identifying people with diabetes are available in France. These algorithms are based either on full insurance coverage for diabetes or on claims of diabetes treatments, or on the combination of these two methods associated with hospitalizations related to diabetes. Each of these algorithms has a different purpose, and the choice should depend on the goal of the study. Algorithms for identifying people treated for dyslipidemia or precocious puberty or who underwent bariatric surgery are also available. Early work from the Redsiam working group in the field of endocrine, nutritional and metabolic diseases produced an inventory of existing algorithms in France, linked with their goals, together with a presentation of their limitations and advantages, providing useful information for the scientific community. This work will continue with discussions about algorithms on the incidence of diabetes in children, thyroidectomy for thyroid nodules, hypothyroidism, hypoparathyroidism, and amyloidosis. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Breast Cancer Lymphatic Dissemination-Influence of Estrogen and Progesterone

DTIC Science & Technology

2007-03-01

Monthly depot injections (.1 mg/body kg) of leuprorelin acetate (LA) and of triptorelin (TR) were continuously administered for 40.4 .7 months to 34...Leuprorelin acetate; Precocious puberty; Thyroid; Triptorelin a a n ( ( a l T r ( a d s h Since the 1980s, long-acting gonadotropin-releasing hor- one...53.4%) received triptorelin depot IM (De- apeptyl, Ipsen Pharma Biotech S.A., Toulon Cedex, rance) at a mean dose of .1 mg/body kg every 28 days (TR

A de novo KMT2D mutation in a girl with Kabuki syndrome associated with endocrine symptoms: a case report.

PubMed

Moon, Jung-Eun; Lee, Su-Jeong; Ko, Cheol Woo

2018-06-18

Kabuki syndrome is characterized by distinctive facial features and varying degrees of growth retardation. It leads to malformations in skeletal, urogenital and cardiac structures; moreover, endocrine conditions such as premature thelarche, precocious puberty, growth hormone deficiency, diabetes insipidus, thyroid dysfunction and obesity have been reported. Kabuki syndrome is caused by a heterozygous mutation in the KMT2D or KDM6A genes. An 11-year-old girl with the typical facial features of Kabuki syndrome visited our hospital due to her short stature. She was found to have the de novo heterozygous mutation of c.8200C > T, p(Arg2734*) in exon 32 of the KMT2D gene and was diagnosed with Kabuki syndrome. The patient also exhibited endocrine abnormalities such as a constitutional delay of puberty, transiently congenial hypothyroidism, obesity and growth hormone deficiency. This is a case of a mutation in the KMT2D gene in a girl with Kabuki syndrome who presented with endocrine symptoms (constitutional delay of puberty, hypothyroidism, obesity and growth hormone deficiency).

Neurokinin B receptor antagonism decreases luteinising hormone pulse frequency and amplitude and delays puberty onset in the female rat.

PubMed

Li, S Y; Li, X F; Hu, M H; Shao, B; Poston, L; Lightman, S L; O'Byrne, K T

2014-08-01

The neural mechanisms controlling puberty onset remain enigmatic. Humans with loss of function mutations in TAC3 or TACR3, the genes encoding neurokinin B (NKB) or its receptor, neurokinin-3 receptor (NK3R), respectively, present with severe congenital gonadotrophin deficiency and pubertal failure. Animal studies have shown ambiguous actions of NKB-NK3R signalling with respect to controlling puberty onset. The present study aimed to determine the role of endogenous NKB-NK3R signalling in the control of pulsatile luteinising hormone (LH) secretion and the timing of puberty onset, and also whether precocious pubertal onset as a result of an obesogenic diet is similarly regulated by this neuropeptide system. Prepubertal female rats, chronically implanted with i.c.v. cannulae, were administered SB222200, a NK3R antagonist, or artificial cerebrospinal fluid via an osmotic mini-pump for 14 days. SB222200 significantly delayed the onset of vaginal opening and first oestrus (as markers of puberty) compared to controls in both normal and high-fat diet fed animals. Additionally, serial blood sampling, via chronic indwelling cardiac catheters, revealed that the increase in LH pulse frequency was delayed and that the LH pulse amplitude was reduced in response to NK3R antagonism, regardless of dietary status. These data suggest that endogenous NKB-NK3R signalling plays a role in controlling the timing of puberty and the associated acceleration of gonadotrophin-releasing hormone pulse generator frequency in the female rat. © 2014 British Society for Neuroendocrinology.

McCune-Albright syndrome: clinical picture and natural history in children and adolescents.

PubMed

Völkl, Thomas M K; Dörr, Helmuth G

2006-05-01

The classical triad of McCune-Albright syndrome (MAS) consists of polyostotic fibrous dysplasia (FD), skin hyperpigmentation (café-au-lait spots), and endocrine dysfunction, frequently seen in females as precocious puberty. Patients with MAS display mosaicism of activating somatic mutations of the alpha-subunit of Gs. Thus, the clinical presentation of each individual is dependent on the particular distribution of affected cells, causing a broad spectrum of endocrine and non-endocrine manifestations. Typical endocrinopathies are precocious puberty, hyperthyroidism, growth hormone excess, hyperprolactemia, and hypercortisolism. The onset of these manifestations is usually during infancy and childhood. Since specific treatment is required, the prognosis depends on the severity of each individual endocrine manifestation. Additionally, there are non-endocrine manifestations, such as fibrous dysplasia of bone (FD), renal phosphate wasting, and skin hyperpigmentation, i.e. café-au-lait spots. FD, mostly polyostotic, causes fractures needing surgical and orthopedic treatment. Since previous studies have suggested the overall prognosis of patients with McCune-Albright syndrome to be non-fatal, recent data have drawn our attention to non-endocrine affections, including hepatobiliary dysfunction and cardiac disease, which are probably an important risk factor for early death. In summary, the clinical picture in MAS is related to its mosaic nature, i.e. any cell, tissue and organ in any site of the body could be affected to varying degrees, ranging from one or two mild clinical signs with excellent long-term prognosis to a severe life-threatening multiorgan disease.

Growing Up with Type 1 Narcolepsy: Its Anthropometric and Endocrine Features

PubMed Central

Ponziani, Virginia; Gennari, Monia; Pizza, Fabio; Balsamo, Antonio; Bernardi, Filippo; Plazzi, Giuseppe

2016-01-01

Study Objectives: To evaluate the effect of type 1 narcolepsy (NT1) on anthropometric and endocrine features in childhood/adolescence, focusing on patterns and correlates of weight, pubertal development, and growth in treated and untreated patients. Methods: We collected anthropometric (height, weight, body mass index (BMI) z-scores), pubertal, metabolic, and endocrine data from 72 NT1 patients at diagnosis and all available premorbid anthropometric parameters of patients from their pediatric files (n = 30). New measurements at 1-y reassessment in patients undergoing different treatments were compared with baseline data. Results: We detected a high prevalence of overweight (29.2%), obesity (25%), metabolic syndrome (18.8%), and precocious puberty (16.1%), but no signs of linear growth alterations at diagnosis. According to anthropometric records, weight gain started soon after NT1 onset. At 1-y follow-up reassessment, sodium oxybate treatment was associated with a significant BMI z-score reduction (−1.29 ± 0.30, p < 0.0005) after adjusting for baseline age, sex, sleepiness, and BMI. Conclusions: NT1 onset in children/adolescents is associated with rapid weight gain up to overweight/obesity and precocious puberty without affecting growth. In our study, sodium oxybate treatment resulted in a significant weight reduction in NT1 overweight/obese patients at 1-y follow-up. Citation: Ponziani V, Gennari M, Pizza F, Balsamo A, Bernardi F, Plazzi G. Growing up with type 1 narcolepsy: its anthropometric and endocrine features. J Clin Sleep Med 2016;12(12):1649–1657. PMID:27707443

Proximal dup(10q): Case report and literature review

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

Barritt, J.A.; Teague, K.E.; Bodurtha, J.N.

We report a case of a proximal dir dup(10q) in a female with multiple congenital anomalies. During infancy she was noted to gave growth retardation, microcephaly, microphthalmia, coloboma, a long, beaked nose, posteriorly rotated ears with simple helices, full bowed lips, widely-spaced nipples, broad first toes, hypermobile and proximally placed thumbs, a heart murmur, PDA, and coarctation of the aorta. Additional findings at age 13 included a full columella, short philtrum, thin limbs, bilateral blindness, and mental retardation, as well as continued growth retardation. Her medical history included precocious puberty at age 8 and a diagnosis of hyperactivity. Using FISHmore » with multiple probes combined with GTG-banding, the aberrant chromosome was determined to be a dir dup(10)(q21{r_arrow}q22). Parental chromosomes were normal and the family history was unremarkable. The parental origin of the dir dup(10) is being assessed using DNA markers. Five similar cases of proximal dup(10q) have been reported previously. Consistent characteristics include low birth weight, developmental and psychomotor delay, growth retardation, and microcephaly. Also found in most cases were short prominent philtrum, bowed mouth, PDA, thin limbs, coloboma, micropthalmia, deep set eyes, and other ocular anomalies. Our case is unique in that she has a long, beaked nose, precocious puberty, and hyperactivity. Future studies such as this, using molecular cytogenetic techniques to better define the chromatin involved in proximal dup(10q), may lead to its recognition as a distinct clinical phenotype.« less

[Primary glucocorticoid resistance syndrome presenting as pseudo-precocious puberty and galactorrhea].

PubMed

Xiang, Shu-lin; He, Li-ping; Ran, Xing-wu; Tian, Hao-ming; Li, Xiu-jun; Liang, Jin-zhong

2008-09-01

Primary glucocorticoid resistance syndrome (PGRS) is a rare condition characterized by hypercortisolism without Cushing's syndrome. This report describes a 7-year-old boy of PGRS with pseudo-precocious puberty and galactorrhea as the main manifestation. His height was 135 cm and body weight was 31 kg. Pigmentation could be seen in the skin, mammary areola and penis. He had hirsutism, low hair line, coarse voice, Tanner stage 3 pubic hair, penis in adult form, accelerated linear growth, and advanced bone age (13 yr.), but normal (for age) testes. Furthermore, he had mammoplasia and galactorrhea. There were no features of glucocorticoid (GC) excess. Hepatic function was impaired (ALT 1426 IU/L, AST 611 IU/L) with no definite causes. Serum cortisol concentration was 1294 nmol/L, 777 nmol/L, 199.3 nmol/L at 8:00, 16:00 and 24:00 respectively. Plasma adrenocorticotropic hormone (ACTH) was normal or a little higher (43.9-80 ng/L). Urinary-free cortisol (UFC) was normal (55.5-62.4 microg/24 h). Serum estradiol (E2), progesterone (P), testosterone (T), luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were normal. Serum dehydroepiandrosterone sulfate (DHEAS, 60 microg/dL) and serum prolactin (PRL, 58.7-183.9 ng/mL) level were high, urinary dehydroepiandrosterone (DHEA) level was also elevated (0.96-3.2 mg/mL). Gonadotrophin hormone-releasing hormone (GnRH) stimulation test was negative. Serum cortisol responded normally to insulin-induced hypoglycemia. However, serum cortisol and plasma ACTH concentration was suppressed to more than 50% by 0.5 mg dexamethasone (DEX). The diagnosis of PGRS was made. TREATMENT AND FOLLOW-UP: The patient received a treatment of 0.75-1.0 mg/d DEX. Because of galactorrhea, bromocriptine was given by 1.25-3.75 mg/d. After 24 months follow-up, the pigmentation was relieved and galactorrhea disappeared. No advanced development of the external genitalia and breast was found. The acceleration of the bone age was also slowed down. But he still had obvious hirsutism. No side effect of DEX was found. PGRS may present with pseudo-precocious puberty and galactorrhea. The aim of treatment in glucocorticoid resistance is to suppress the excessive secretion of ACTH and the increased production of adrenal androgens. The administration of synthetic GC with minimal intrinsic mineralocorticoid activity, such as DEX, provides a rational treatment for PGRS. Long-term DEX treatment should be individualized and carefully titrated based on the clinical manifestations and biochemical profile in order to control the clinical manifestations of the disease.

Assessment of pubertal development in Egyptian girls.

PubMed

Hosny, Laila A; El-Ruby, Mona O; Zaki, Moushira E; Aglan, Mona S; Zaki, Maha S; El Gammal, Mona A; Mazen, Inas M

2005-06-01

Puberty is a significant event of human growth and maturation associated with marked physiological and psychological changes. The aim of this study was to assess normal pubertal development in Egyptian girls to define normal, precocious and delayed puberty. The present study included a cross-sectional sample of 1,550 normal Egyptian girls of high and middle socioeconomic class living in Cairo. Their ages ranged from 6.5 to 18.5 years. Pubertal assessment was made according to Tanner staging. The mean menarcheal age (MMA) was estimated using probit analysis. Weight and height were measured and body mass index (BMI) was calculated. The mean age at breast bud stage (B2) was 10.71+/-1.6, pubic hair stage (PH2) was 10.46+/-1.36, while axillary hair stage (A2) was 11.65+/-1.62 and MMA was 12.44 years. The mean age at attainment of puberty was compared with those of other Egyptian studies and other populations. Girls of the present study started pubertal development and achieved menarche earlier than those of previous Egyptian studies confirming a secular trend. Differences between the present study and other worldwide studies can be attributed to various genetic, racial, geographical, nutritional, and secular trend factors.

[McCune-Albright syndrome revealed by Blaschko-linear café-au-lait spots on the back].

PubMed

Jung, A-J; Soskin, S; Paris, F; Lipsker, D

2016-01-01

McCune-Albright syndrome is a rare sporadic disease defined by the triad of café-au-lait spots, fibrous dysplasia of bone and endocrine disorder. Diagnosis is classically confirmed by the presence of bone lesions or precocious puberty. We report a case of McCune-Albright syndrome diagnosed solely on the basis of the cutaneous signs. A four-year-old girl was seen in our clinic due to the presence of congenital café-au-lait spots on her back. These macules were irregular, with jagged borders, and were disposed in a broad band on the left shoulder and in the lumbar region, in a Blaschko-linear pattern. McCune-Albright syndrome was immediately suspected, despite the absence of other signs of the disease. Genetic assessment carried out a year and a half later confirmed the diagnosis, with arginine substitution at position 201 of Gs alpha protein. The child was still asymptomatic. Regular radiographic and endocrine assessments remained normal for three years until the sudden appearance at the age of seven years of precocious puberty and radiographic evidence of fibrous dysplasia of the right hand. Café-au-lait spots are very common in the general population. An underlying genetic disorder should only be sought when such spots are multiple. However, in the case of McCune-Albright syndrome, it is the irregular borders and the Blaschko-linear arrangement of the spots in broad irregular bands that are pathognomonic, reflecting as they do the genetic mosaicism characteristic of this disease. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

McCune-Albright syndrome.

PubMed

Dumitrescu, Claudia E; Collins, Michael T

2008-05-19

McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS.

McCune-Albright syndrome

PubMed Central

Dumitrescu, Claudia E; Collins, Michael T

2008-01-01

McCune-Albright syndrome (MAS) is classically defined by the clinical triad of fibrous dysplasia of bone (FD), café-au-lait skin spots, and precocious puberty (PP). It is a rare disease with estimated prevalence between 1/100,000 and 1/1,000,000. FD can involve a single or multiple skeletal sites and presents with a limp and/or pain, and, occasionally, a pathologic fracture. Scoliosis is common and may be progressive. In addition to PP (vaginal bleeding or spotting and development of breast tissue in girls, testicular and penile enlargement and precocious sexual behavior in boys), other hyperfunctioning endocrinopathies may be involved including hyperthyroidism, growth hormone excess, Cushing syndrome, and renal phosphate wasting. Café-au-lait spots usually appear in the neonatal period, but it is most often PP or FD that brings the child to medical attention. Renal involvement is seen in approximately 50% of the patients with MAS. The disease results from somatic mutations of the GNAS gene, specifically mutations in the cAMP regulating protein, Gs alpha. The extent of the disease is determined by the proliferation, migration and survival of the cell in which the mutation spontaneously occurs during embryonic development. Diagnosis of MAS is usually established on clinical grounds. Plain radiographs are often sufficient to make the diagnosis of FD and biopsy of FD lesions can confirm the diagnosis. The evaluation of patients with MAS should be guided by knowledge of the spectrum of tissues that may be involved, with specific testing for each. Genetic testing is possible, but is not routinely available. Genetic counseling, however, should be offered. Differential diagnoses include neurofibromatosis, osteofibrous dysplasia, non-ossifying fibromas, idiopathic central precocious puberty, and ovarian neoplasm. Treatment is dictated by the tissues affected, and the extent to which they are affected. Generally, some form of surgical intervention is recommended. Bisphosphonates are frequently used in the treatment of FD. Strengthening exercises are recommended to help maintaining the musculature around the FD bone and minimize the risk for fracture. Treatment of all endocrinopathies is required. Malignancies associated with MAS are distinctly rare occurrences. Malignant transformation of FD lesions occurs in probably less than 1% of the cases of MAS. PMID:18489744

Detrimental Psychological Outcomes Associated with Early Pubertal Timing in Adolescent Girls

PubMed Central

Mendle, Jane; Turkheimer, Eric; Emery, Robert E.

2010-01-01

Though often discussed as though it were a discrete event, puberty comprises one segment of a larger developmental continuum and is notable for rapid transformation across a multitude of domains. Research suggests that an earlier rate of pubertal maturation in girls correlates with a number of detrimental outcomes compared with on-time or later maturation. The present review synthesizes the research on negative psychological sequelae of early pubertal timing in adolescent girls. Emphasis is on three theoretical perspectives by which precocious development is believed to affect the emergence of adverse outcomes: biological, psychosocial, and selection effects. PMID:20740062

Long-term betacarotene-supplementation enhances serum insulin concentrations without effect on the onset of puberty in the female goat.

PubMed

Meza-Herrera, Cesar A; Hernández-Valenzuela, Luis C; González-Bulnes, Antonio; Tena-Sempere, Manuel; Abad-Zavaleta, Jose; Salinas-Gonzalez, Homero; Mellado, Miguel; Veliz-Deras, Francisco

2011-11-01

The effect of betacarotene (BC) supplementation on the onset of puberty and serum insulin levels in goats was evaluated in the study. In June, prepuberal goats (n=17; 3 months old; 7/8 Saanen-Alpine; 26° NL) were randomly assigned to one of two groups: 1/ betacarotene group supplemented daily with 50 mg of BC (n=9; live weight [LW]: 17.3±1.0 kg; body condition score [BCS]: 3.34±0.12) or 2/ control group (CONT; n=8; LW:16.1±1.0 kg; BCS=3.17±0.12). From June to November, an intermittent blood sampling was performed twice per week in both groups to evaluate serum progesterone (P(4)), while monthly samples were intended for insulin (INS) determination. Initial mean LW (16.7±1.0 kg) and BCS (3.31±0.12) were similar (p>0.05) in both groups. Mean serum insulin (1.37 vs. 1.18±0.09 ng/ml), age of puberty (215.7 vs. 226.5±6.6 days) and the percentage of goats reaching puberty (44.4 vs. 25.0±17.0%) did not differ (p>0.05) between BC and CONT group, respectively. However, increase in serum insulin during the second half of the experiment was observed in BC group (p<0.05) which was positively correlated with LW (r=0.95; p<0.05). In addition, as LW (r=-0.89) and serum insulin (r=-0.76) levels increased, the natural photoperiod decreased, revealing negative correlations (p<0.05) between the respective variables. In this study, BC supplementation did not promote precocious puberty and did not affect the percentage of goats reaching activation of the hypothalamic-hypophyseal-gonadal axis during the establishment of puberty. Nonetheless, BC supplementation positively affected the release pattern of insulin suggesting a potential role of BC as pancreas-activating molecule.

DEHP exposure in utero disturbs sex determination and is potentially linked with precocious puberty in female mice.

PubMed

Wang, Yongan; Yang, Qing; Liu, Wei; Yu, Mingxi; Zhang, Zhou; Cui, Xiaoyu

2016-09-15

Human's ubiquitous exposure to di (2-ethylhexyl) phthalate (DEHP) is thought to be associated with female reproductive toxicity. Previous studies found that DEHP inhibited follicle growth and decreased estradiol levels in adult female mice. However, limited information is available on the link between in utero DEHP exposure and ovarian development in female mouse offspring. The present study evaluates the disturbances in regulatory genes involved in female sex determination and the ovarian outcomes in fetal and postnatal female mice treated with in utero DEHP exposure. Pregnant mice were exposed to DEHP by gavage, with the dosage regime beginning at human relevant exposure levels. After in utero DEHP exposure, increased follicular atresia was observed in the female pups at postnatal days (PND) 21. Foxl2 expression was significantly upregulated, and Fst was significantly downregulated by DEHP above 2mg/kg/d at PND 1 and 21. This suggests that lesion of granulosa cell differentiation and disturbance of follicle development in postnatal female mice. The expression of Cyp11a1 and Star were significantly downregulated by in utero DEHP exposure, indicating effects on estradiol biosynthesis. The female sex determination pathway was disturbed in fetus by DEHP at 2mg/kg/d and above during the critical time window of sex determination causing significant upregulation of Foxl2, Wnt4, β-catenin and Fst. Furthermore, the increased expression of Wnt4 was supported by whole-mount in situ hybridization (WISH). These results suggest a possible association between in utero DEHP exposure and precocious puberty in the postnatal life of mice offspring, where disturbance of the sex determination regulating pathway acted as an important mechanism. Copyright © 2016 Elsevier Inc. All rights reserved.

Constitutive luteinizing hormone receptor signaling causes sexual dysfunction and Leydig cell adenomas in male mice.

PubMed

Hai, Lan; Hiremath, Deepak S; Paquet, Marilène; Narayan, Prema

2017-05-01

The luteinizing hormone receptor (LHCGR) is necessary for fertility, and genetic mutations cause defects in reproductive development and function. Activating mutations in LHCGR cause familial male-limited precocious puberty (FMPP). We have previously characterized a mouse model (KiLHRD582G) for FMPP that exhibits the same phenotype of precocious puberty, Leydig cell hyperplasia, and elevated testosterone as boys with the disorder. We observed that KiLHRD582G male mice became infertile by 6 months of age, although sperm count and motility were normal. In this study, we sought to determine the reason for the progressive infertility and the long-term consequences of constant LHCGR signaling. Mating with superovulated females showed that infertile KiLHRD582G mice had functional sperm and normal accessory gland function. Sexual behavior studies revealed that KiLHRD582G mice mounted females, but intromission was brief and ejaculation was not achieved. Histological analysis of the reproductive tract showed unique metaplastic changes resulting in pseudostratified columnar epithelial cells with cilia in the ampulla and chondrocytes in the penile body of the KiLHRD582G mice. The infertile KiLHRD582G exhibited enlarged sinusoids and a decrease in smooth muscle content in the corpora cavernosa of the penile body. However, collagen content was unchanged. Leydig cell adenomas and degenerating seminiferous tubules were seen in 1-year-old KiLHRD582G mice. We conclude that progressive infertility in KiLHRD582G mice is due to sexual dysfunction likely due to functional defects in the penis. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please journals.permissions@oup.com.

Exposure to phthalates: reproductive outcome and children health. A review of epidemiological studies.

PubMed

Jurewicz, Joanna; Hanke, Wojciech

2011-06-01

Phthalates are a family of industrial chemicals that have been used for a variety of purposes. As the potential consequences of human exposure to phthalates have raised concerns in the general population, they have been studied in susceptible subjects such as pregnant women, infants and children. This article aims at evaluating the impact of exposure to phthalates on reproductive outcomes and children health by reviewing most recent published literature. Epidemiological studies focusing on exposure to phthalates and pregnancy outcome, genital development, semen quality, precocious puberty, thyroid function, respiratory symptoms and neurodevelopment in children for the last ten years were identified by a search of the PubMed, Medline, Ebsco, Agricola and Toxnet literature bases. The results from the presented studies suggest that there are strong and rather consistent indications that phthalates increase the risk of allergy and asthma and have an adverse impact on children's neurodevelopment reflected by quality of alertness among girls, decreased (less masculine) composite score in boys and attention deficit hyperactivity disorder. Results of few studies demonstrate negative associations between phthalate levels commonly experienced by the public and impaired sperm quality (concentration, morphology, motility). Phthalates negatively impact also on gestational age and head circumference; however, the results of the studies were not consistent. In all the reviewed studies, exposure to phthalates adversely affected the level of reproductive hormones (luteinizing hormone, free testosterone, sex hormone-binding globulin), anogenital distance and thyroid function. The urinary levels of phthalates were significantly higher in the pubertal gynecomastia group, in serum in girls with premature thelarche and in girls with precocious puberty. Epidemiological studies, in spite of their limitations, suggest that phthalates may affect reproductive outcome and children health. Considering the suggested health effects, more epidemiologic data is urgently needed and, in the meantime, precautionary policies must be implemented.

Effects and safety of combination therapy with gonadotropin-releasing hormone analogue and growth hormone in girls with idiopathic central precocious puberty: a meta-analysis.

PubMed

Liu, S; Liu, Q; Cheng, X; Luo, Y; Wen, Y

2016-10-01

This meta-analysis is to evaluate the effects and safety of the combination therapy for girls with idiopathic central precocious puberty (ICPP). Electronic databases were searched for randomized controlled trials (RCTs) and clinical controlled trials (CCTs) that adopted gonadotropin-releasing hormone analogue (GnRHa) therapy and GnRHa plus growth hormone (GH) combination therapy to treat ICPP girls. A total of six RCTs (162 patients) and six CCTs (247 patients) were included. Compared to the GnRHa therapy group, the combination therapy group achieved taller final height (mean difference, MD = 2.81 cm, 95 % CI 1.76-3.87, four CCTs; MD = 4.30 cm, 95 % CI 0.59-8.01, one RCT); greater progression of final height compared with target height (MD = 3.92 cm, 95 % CI 3.12-4.73, four CCTs; MD = 4.00 cm, 95 % CI 1.93-6.07, One RCT) and larger height gains (MD = 3.49 cm, 95 % CI 0.97-6.01, four CCTs; MD = 3.88 cm, 95 % CI 0.15-7.61, one RCT). No severe adverse effects of treatment were reported. For ICPP girls, the GnRHa and GH combination therapy had advantages over GnRHa alone on final height and no severe adverse effects were reported. We recommend comprehensive assessment of the individual growth rate, patient compliance, the clinical effects, the height expectations of individual patients and the treatment cost to the family in order to identify the best therapy for individual patients.

Association between Small Fetuses and Puberty Timing: A Systematic Review and Meta-Analysis

PubMed Central

Deng, Xu; Li, Wenyan; Luo, Yan; Liu, Shudan; Wen, Yi; Liu, Qin

2017-01-01

Background: Epidemiological studies reporting the effect of small fetuses (SF) on puberty development have shown inconsistent results. Objective: To examine current study evidence and determine the strength and direction of the association between SF and puberty timing. Methods: PubMed, OVID, Web of Science, EBSCO, and four Chinese databases were searched from their date of inception to February 2016. All cohort studies that examined the association between SF and puberty timing in children were identified. Two reviewers independently screened the studies, assessed the quality of included studies, and extracted the data. The quality of the included cohort studies was assessed by the Newcastle–Ottawa Scale. Risk ratio (RR), Weighted Mean Difference (WMD), and 95% confidence intervals (CIs) were calculated and pooled by RevMan5.3 (Cochrane Collaboration, London, UK). Results: A total of 10 cohort studies involving 2366 subjects was included in the final analysis. The pooled estimates showed that SF did not significantly increase the number of pubertal children in boys (RR: 0.97; 95% CI: 0.82 to 1.15), or in girls (RR: 0.91; 95% CI: 0.79 to 1.04). Compared with the control group, the SF group had an earlier onset of puberty in girls (WMD: −0.64; 95% CI: −1.21 to −0.06), and in precocious pubarche (PP) girls (WMD: −0.10; 95% CI: −0.13 to −0.07). There was no difference in the onset of puberty in boys (WMD: −0.48; 95% CI: −1.45 to 0.50) between SF and control groups. The pooled result indicated an earlier age at menarche in girls born small for gestational age (WMD: −0.30; 95% CI: −0.58 to −0.03), but no difference in the age at menarche in the SF group of PP girls. Conclusions: SF may be associated with an earlier age of onset of puberty, especially among girls, as well as earlier age at menarche for girls. Well-designed studies with larger sample sizes and long-term follow-up among different countries and ethnicities are needed. PMID:29137163

Association between Small Fetuses and Puberty Timing: A Systematic Review and Meta-Analysis.

PubMed

Deng, Xu; Li, Wenyan; Luo, Yan; Liu, Shudan; Wen, Yi; Liu, Qin

2017-11-13

Background : Epidemiological studies reporting the effect of small fetuses (SF) on puberty development have shown inconsistent results. Objective : To examine current study evidence and determine the strength and direction of the association between SF and puberty timing. Methods : PubMed, OVID, Web of Science, EBSCO, and four Chinese databases were searched from their date of inception to February 2016. All cohort studies that examined the association between SF and puberty timing in children were identified. Two reviewers independently screened the studies, assessed the quality of included studies, and extracted the data. The quality of the included cohort studies was assessed by the Newcastle-Ottawa Scale. Risk ratio (RR), Weighted Mean Difference (WMD), and 95% confidence intervals (CIs) were calculated and pooled by RevMan5.3 (Cochrane Collaboration, London, UK). Results : A total of 10 cohort studies involving 2366 subjects was included in the final analysis. The pooled estimates showed that SF did not significantly increase the number of pubertal children in boys (RR: 0.97; 95% CI: 0.82 to 1.15), or in girls (RR: 0.91; 95% CI: 0.79 to 1.04). Compared with the control group, the SF group had an earlier onset of puberty in girls (WMD: -0.64; 95% CI: -1.21 to -0.06), and in precocious pubarche (PP) girls (WMD: -0.10; 95% CI: -0.13 to -0.07). There was no difference in the onset of puberty in boys (WMD: -0.48; 95% CI: -1.45 to 0.50) between SF and control groups. The pooled result indicated an earlier age at menarche in girls born small for gestational age (WMD: -0.30; 95% CI: -0.58 to -0.03), but no difference in the age at menarche in the SF group of PP girls. Conclusions : SF may be associated with an earlier age of onset of puberty, especially among girls, as well as earlier age at menarche for girls. Well-designed studies with larger sample sizes and long-term follow-up among different countries and ethnicities are needed.

McCune-Albright syndrome: radiological and MR findings.

PubMed

Yongjing, G; Huawei, L; Zilai, P; Bei, D; Hao, J; Kemin, C

2001-01-01

McCune-Albright syndrome (MAS) is a non-inherited disorder due to the GNAS1 gene mutation. The syndrome is characterized with the triad of polyostotic fibrous dysplasia, pigmented skin lesions, endocrinopathy, and precocious puberty. We report the case of a 14-year-old boy, presenting with sclerotic type of polyostotic fibrous dysplasia. Radiological methods including plain X-ray film, MR and whole body bone scintigraphy suggested the diagnosis of MAS. MRI provided more directly perceived images and it was more sensitive in demonstrating the lesion: its shape, contents, especially the size of the affected region. Histopathological study and the identification of mutant gene finally confirmed the diagnostic result.

Efficacy and Safety of Gonadotropin-Releasing Hormone Agonist Treatment to Suppress Puberty in Gender Dysphoric Adolescents.

PubMed

Schagen, Sebastian E E; Cohen-Kettenis, Peggy T; Delemarre-van de Waal, Henriette A; Hannema, Sabine E

2016-07-01

Puberty suppression using gonadotropin-releasing hormone agonists (GnRHas) is recommended by current guidelines as the treatment of choice for gender dysphoric adolescents. Although GnRHas have long been used to treat precocious puberty, there are few data on the efficacy and safety in gender dysphoric adolescents. Therefore, the Endocrine Society guideline recommends frequent monitoring of gonadotropins, sex steroids, and renal and liver function. To evaluate the efficacy and safety of GnRHa treatment to suppress puberty in gender dysphoric adolescents. Forty-nine male-to-female and 67 female-to-male gender dysphoric adolescents treated with triptorelin were included in the analysis. Physical examination, including assessment of Tanner stage, took place every 3 months and blood samples were drawn at 0, 3, and 6 months and then every 6 months. Body composition was evaluated using dual energy x-ray absorptiometry. GnRHa treatment caused a decrease in testicular volume in 43 of 49 male-to-female subjects. In one of four female-to-male subjects who presented at Tanner breast stage 2, breast development completely regressed. Gonadotropins and sex steroid levels were suppressed within 3 months. Treatment did not have to be adjusted because of insufficient suppression in any subject. No sustained abnormalities of liver enzymes or creatinine were encountered. Alkaline phosphatase decreased, probably related to a slower growth velocity, because height SD score decreased in boys and girls. Lean body mass percentage significantly decreased during the first year of treatment in girls and boys, whereas fat percentage significantly increased. Triptorelin effectively suppresses puberty in gender dysphoric adolescents. These data suggest routine monitoring of gonadotropins, sex steroids, creatinine, and liver function is not necessary during treatment with triptorelin. Further studies should evaluate the extent to which changes in height SD score and body composition that occur during GnRHa treatment can be reversed during subsequent cross-sex hormone treatment. Copyright © 2016 International Society for Sexual Medicine. Published by Elsevier Inc. All rights reserved.

[Final height in symptomatic boys with late-onset adrenal hyperplasia (LOCAH), treated with glucocorticoids. Clinical cases].

PubMed

Pasqualini, Titania; Alonso, Guillermo; Fernández, Cecilia; Buzzalino, Noemí; Dain, Liliana

2013-04-01

Although corticoid replacement is recommended for those late-onset adrenal hyperplasia with clinical manifestations, asymptomatic patients do not need treatment. We describe clinical features at diagnosis, treatment, and growth till adult- height, in 4 boys. At diagnosis, age ranged from 9.2-11.6 years. The initial symptoms/signs were: precocious pubarche (n = 2), accelerated bone age (n = 1) and precocious puberty (n = 1). All of them presented elevated 17 hydroxyprogesterone levels and were compound heterozygotes carrying p.V281L mutation. Since, at diagnosis, bone age was significantly advanced for chronological age (13.1 ± 0.5 vs. 10.2 ± 1.1 p = 0.008), hydrocortisone therapy was initiated. During follow-up, mean height Z score decreased 1.4 ± 0.4 SDS (p = 0.007), though adult mean height was not different from target height (-0.39 ± 0.7 vs. -0.04 ± 0.5 SDS, p = 0.054). In conclusion, in 4 symptomatic patients, accurate treatment of late-onset adrenal hyperplasia led to an adult mean height not different from target height. Advanced bone age at diagnosis and the loss of height during pubertal development suggest the need of therapy.

Kisspeptin and KISS1R: a critical pathway in the reproductive system

PubMed Central

Gianetti, Elena; Seminara, Stephanie

2010-01-01

In 2003, three groups around the world simultaneously discovered that KISS1R (GPR54) is a key gatekeeper of sexual maturation in both mice and men. Developmental changes in the expression of the ligand for KISS1R, kisspeptin, support its critical role in the pubertal transition. In addition, kisspeptin, a powerful stimulus of GNRH-induced gonadotropin secretion and may modulate both positive and negative sex steroid feedback effects at the hypothalamic level. Genetic studies in humans have revealed both loss-of-function and gain-of-function mutations in patients with idiopathic hypogonadotropic hypogonadism and precocious puberty respectively. This review examines the kisspeptin/KISS1R pathway in the reproductive system. PMID:18515314

The missing "Bratz" doll: a case of vaginal foreign body.

PubMed

Someshwar, Jean; Lutfi, Riad; Nield, Linda S

2007-12-01

Young female patients with gynecologic complaints, including vaginal discharge, commonly seek care in the emergency department. Prepubertal vaginal discharges have various potential etiologies including nonspecific vulvovaginitis, infections, inflammatory or dermatologic processes, precocious puberty, malignancy, anatomical anomaly, trauma, sexual abuse, and foreign body. We present the case of a 4-year-old girl with vaginal odor and discharge secondary to a foreign body. The foreign body was part of a toy, the lower half of the patient's missing "Bratz" (MGA Entertainment) doll. Although it is well known that a vaginal foreign body can cause a vaginal discharge, the unusual nature of the foreign body in this case and the revealing radiograph made this a case of particular interest.

Psychosexual development, maternalism, nonpromiscuity, and body image in 15 females with precocious puberty.

PubMed

Money, J; Walker, P A

1971-03-01

Fifteen females with a history of idiopathic sexual precocity were selected without known sampling bias. They had been followed for as long as 18 years. They showed various behavioral characteristics as a group, but were also individually unique. If the IQ permitted, they benefited socially from school acceleration. Left to their own devices, the majority preferred friends nearer to them in physique age rather than chronologic age. Play interests, though influenced by the age of playmates, showed no features unique to the precocious onset of hormonal puberty. About half of the girls had occasional moody or depressed spells and wanted to be left alone. Maternalistic interests were strongly represented; only one girl was a tomboy. Masturbation and sexual play in childhood were rarely confirmed, and in no instances were totally contrary to family or community mores. No consistent progression of erotic dream content was discerned. Dreams of having a baby were rare, but antedated intercourse dreams, which were also rarely reported and did not include sensations of climax. Whereas the youngest age of having a serious boyfriend was 8 years, and the youngest age of intercourse, 11, the majority of girls did not report romantic and sexual involvements before the middle teenage years or later. In the three instances of marriage, the youngest was at age 21. Motherhood has so far been achieved by only one patient. She delivered her first child at age 11. The visible appearance of early sexual development and early advanced statural growth created a problem in childhood human relationships for most of the girls, regardless of what they said, and regardless of their skill or ineptitude in handling it. They all benefited even from minimal counseling, as did their parents. Early appearance of physical sexual development does not automatically lead to premature engagement in erotic activity or promiscuous sexual behavior. Such activity and behavior require appropriate experience and facilitating knowledge of erotic opportunities.

Long-term Outcomes of Letrozole Treatment for Precocious Puberty in Girls with McCune-Albright Syndrome

PubMed Central

Brillante, Beth A.; Guthrie, Lori C.; Gafni, Rachel I.; Collins, Michael T.

2016-01-01

Objective McCune-Albright syndrome (MAS) is a rare disorder with a spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Design Retrospective cohort analysis. Methods Clinical data were reviewed, including history and physical, bone age, and pelvic ultrasounds on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height, and adult height. Results Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1SD) (0.5–10.9, range) and mean follow-up was 6.0 ± 3.3 years (range 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR 2.3) to 0.5 (IQR 0.4) (p<0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to −0.6 ± 1.6 (p = 0.0004). Predicted adult height Z-scores increased significantly from −2.9 ± 3.2 to −0.8 ± 1.5 for subjects on treatment (p = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from −1.5 to 1.7 (median −0.6), which was increased in comparison to untreated historical controls (p=0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. Conclusions In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. PMID:27562402

Association of PAEs with Precocious Puberty in Children: A Systematic Review and Meta-Analysis.

PubMed

Wen, Yi; Liu, Shu-Dan; Lei, Xun; Ling, Yu-Shuang; Luo, Yan; Liu, Qin

2015-12-01

Precocious puberty (PP) currently affects 1 in 5000 children and is 10 times more common in girls. Existing studies have tried to detect an association between phathalic acid esters (PAEs) and PP, but the results did not reach a consensus. To estimate the association between PAEs and children with PP based on current evidence. Databases including PubMed (1978 to March 2015), OVID (1946 to March 2015), Web of Science (1970 to March 2015), EBSCO (1976 to March 2015), CNKI (1979 to March 2015), WANFANG DATA (1987 to March 2015), CBM (1978 to March 2015) and CQVIP (1989 to March 2015) were searched to identify all case-control studies that determined the exposure and concentration of PAEs and their metabolites in children with PP. Meta-analysis of the pooled standard mean difference (SMD) and odds ratio (OR) with 95% confidence intervals (CI) were calculated. A total of 14 studies involving 2223 subjects were finally included. The pooled estimates showed that PP was associated with di-(2-ethylhexyl)-phthalate (DEHP) exposure (OR: 3.90, 95% CI: 2.77 to 5.49). Besides, the concentration of DEHP (SMD: 1.73, 95% CI: 0.54 to 2.91) and di-n-butyl phthalate (DBP) (SMD: 4.31, 95% CI: 2.67 to 5.95) in the PP group were significantly higher than those in the control group, respectively, while no difference was detected between case and control groups in either serum or urinary concentration of mono-(2-ethylhexyl)-phthalate (MEHP), monobutyl phthalate (MBP), mono(2-ethyl-5-oxohexyl) phthalate(MEOHP), mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), monomethyl phthalate (MMP), monobenzyl phthalate (MBzP) or monoethyl phthalate (MEP). Exposure of DEHP and DBP might be associated with PP risk for girls, however, there is no evidence to show an association between the exposure to most PAE metabolites and PP. Given the moderate strength of the results, well-designed cohort studies with large sample size should be performed in future.

A longitudinal study of the physical growth and health of postinstitutionalized Romanian adoptees

PubMed Central

Le Mare, Lucy; Audet, Karyn

2006-01-01

In the present longitudinal study, the physical growth and health of 36 early-deprived postinstitutionalized Romanian orphans (ROs; 17 boys) adopted by Canadian families are documented. Data were collected for each child at three time points: at 11 months postadoption, at 4.5 years of age and at 10.5 years of age. Data from the RO children were compared with those from children in two matched comparison groups (Canadian-born [CB] nonadopted children and early-adopted [EA] Romanian children without institutional experience). Results indicated that there was considerable growth retardation in the RO children at times 1 and 2. Nonsignificant differences in height and weight among the RO, CB and EA groups were obtained at time 3, indicating significant growth catch-up. Precocious puberty, a documented feature of some postinstitutionalized children, was not observed in the present study population. At time 3, the RO children did not differ from the CB or EA children on indicators of puberty. The poor physical health of the RO children at time 1 was no longer apparent at time 3. According to parent reports, the RO children were equally as healthy as the CB and EA children. PMID:19030260

Changes in the concentrations of testosterone and androstenedione in the plasma and testis of the guinea-pig from birth to death.

PubMed

Rigaudière, N; Pelardy, G; Robert, A; Delost, P

1976-11-01

Testosterone and androstenedione concentrations in the plasma and testis of male guinea-pigs were estimated by gas chromatography at intervals (36 stages) from birth to death. Four main periods of androgenic activity were recognized. The neonatal period, from birth to Day 16, is characterized by a precocious but transient peak in plasma testosterone concentration at Days 2 and 3. The pubertal period from Days 16 to 90 can be subdivided into a prepubertal period starting on Day 16 and marked by a sudden linear increase in plasma and testicular testosterone concentration together with an increase in testicular and seminal vesicle weight, and a postpubertal period, from Day 50 (the time of hormonal puberty) to Day 90, characterized by high and stable androgen levels while testicular and genital tract development continues. Adulthood spans the period between Months 3-6 and Month 24; plasma and testicular concentrations of testosterone and androstenedione are stable but lower than those observed during puberty. The period of senescence occurs between Months 24 and 28 and is marked by a fall in testosterone secretion and involution of the seminiferous tubules and accessory sex glands.

Van Wyk Grumbach Syndrome: A Rare Consequence of Hypothyroidism.

PubMed

Reddy, Pavan; Tiwari, Kritika; Kulkarni, Abhishek; Parikh, Ketan; Khubchandani, Raju

2018-05-19

Long standing hypothyroidism presenting as an ovarian mass has been well described in literature as the Van Wyk Grumbach syndrome (hypothyroidism, isosexual precocious puberty and ovarian mass). Here, authors report this entity in a 11 y 7 mo old girl child who was referred to a surgeon in view of intestinal obstruction along with a multiloculated ovarian cyst. On evaluation, she was found to have raised serum creatinine, short stature, delayed bone age and pituitary enlargement. She was diagnosed with autoimmune thyroiditis and was started on replacement therapy with thyroxine, after which the ovarian cysts regressed. This entity should be kept in mind in cases of ovarian cysts, especially those with isosexual precocity, to prevent unnecessary evaluation and surgical misadventures.

Juvenile granulosa cell ovarian tumor: a case report and review of literature.

PubMed

Sivasankaran, Sujatha; Itam, Paul; Ayensu-Coker, Leslie; Sanchez, Judith; Egler, Rachel A; Anderson, Matthew L; Brandt, Mary L; Dietrich, Jennifer E

2009-10-01

Juvenile granulosa cell tumors (JGCT) are rare ovarian tumors that frequently present with precocious puberty. Presentation in infants less than a year of age is also rare. We describe a 10-month-old infant who presented with both premature thelarche and adrenarche due to JGCT. Laboratory evaluation revealed classic elevation of estradiol and inhibin B, and less classic elevation of total and free testosterone. Oophorectomy and staging resulted in a diagnosis of Stage IA JGCT. Survival rates are >95% among patients diagnosed under 10 years of age. Tumor recurrence is rare but can occur as late as 48 months. Therefore, tumor surveillance is warranted for patients with even a Stage IA JGCT and involves monitoring serial inhibin B levels along with intermittent imaging.

[Clinical thinking and decision making in practice. A 7-year old boy with rapid growth and pubic hair].

PubMed

Berents-Oosterhof, M Y; Noordam, C; Otten, B J

2000-12-16

A 7-year-old boy was tall, with a developing penis and initial growth of pubic hair. Due to the accelerated growth there was no premature adrenarche and due to the increased testicular volume there must have been a central cause for the production of androgens. Further specific investigations revealed an astrocytoma of the hypothalamus. After radiotherapy, the tumour exhibited no growth. The pubertal development was inhibited and the growth later stimulated by means of medication. In the case of pubertas praecox the growth chart and pubertal stages including testicular volume can help to differentiate between central and peripheral precocious puberty, narrow the diagnostic evaluation and reduce the time of the initial therapy.

Precocious pseudopuberty due to an autonomous ovarian follicular cyst: case report with a review of literatures

PubMed Central

2013-01-01

Background Small follicular cysts are commonly found in the ovaries of prepubertal girls, and in most cases, they are of no clinical importance. These cysts are usually self-limiting and resolve spontaneously. However, occasionally, these cysts may enlarge and continue to produce estrogen, resulting in signs of sexual precocity. Here, we report a case of precocious pseudopuberty associated with an autonomous ovarian follicular cyst. Case presentation A 5.9-year-old girl initially presented to a local clinic with vaginal bleeding and a large unilateral ovarian cyst. At 6 months after the initial acute episode, the patient visited our hospital as the ovarian cyst had persisted and increased in size. Endocrinological examination showed elevated estrogen levels and suppressed gonadotropin levels on GnRH stimulation test. Also, no skin pigmentation or bone anomaly was noted. Based on these observations, laparoscopic cystectomy was performed, and histologic analysis confirmed the diagnosis of a follicular cyst. After the laparoscopic cystectomy, the patient’s hormone levels returned to normal and no ovarian cyst was detected by ultrasound. Conclusions As autonomous ovarian cysts are usually self-limiting disorder, no treatment is necessary. Therefore, surgical management should be deferred as long as possible to avoid the risk of repeat surgery, as pseudoprecocious puberty due to autonomous ovarian cysts can resolve spontaneoulsy and frequently recurs. Precocious pseudopuberty with an ovarian cyst may be due to granulosa cell tumor or may be one symptom of the McCune-Albright Syndrome (MAS). A careful longer-term follow up of patients with autonomous ovarian cysts and/or molecular studies may be necessary in such cases. PMID:23937919

Pubertal development and primary ovarian insufficiency in female survivors of embryonal brain tumors following risk-adapted craniospinal irradiation and adjuvant chemotherapy.

PubMed

DeWire, Mariko; Green, Daniel M; Sklar, Charles A; Merchant, Thomas E; Wallace, Dana; Lin, Tong; Vern-Gross, Tamara; Kun, Larry E; Krasin, Matthew J; Boyett, James M; Wright, Karen D; Wetmore, Cynthia; Broniscer, Alberto; Gajjar, Amar

2015-02-01

Female survivors of central nervous system (CNS) tumors are at an increased risk for gonadal damage and variations in the timing of puberty following radiotherapy and alkylating agent-based chemotherapy. Clinical and laboratory data were obtained from 30 evaluable female patients with newly diagnosed embryonal CNS tumors treated on a prospective protocol (SJMB 96) at St. Jude Children's Research Hospital (SJCRH). Pubertal development was evaluated by Tanner staging. Primary ovarian insufficiency (POI) was determined by Tanner staging and FSH level. Females with Tanner stage I-II and FSH > 15 mIU/ml, or Tanner stage III-V, FSH > 25 mIU/ml and FSH greater than LH were defined to have ovarian insufficiency. Recovery of ovarian function was defined as normalization of FSH without therapeutic intervention. Median length of follow-up post completion of therapy was 7.2 years (4.0-10.8 years). The cumulative incidence of pubertal onset was 75.6% by the age of 13. Precocious puberty was observed in 11.1% and delayed puberty in 11.8%. The cumulative incidence of POI was 82.8%, though recovery was observed in 38.5%. Treatment for primary CNS embryonal tumors may cause variations in the timing of pubertal development, impacting physical and psychosocial development. Female survivors are at risk for POI, a subset of whom will recover function over time. Further refinement of therapies is needed in order to reduce late ovarian insufficiency. Pediatr Blood Cancer 2015;62:329-334. © 2014 Wiley Periodicals, Inc. © 2014 Wiley Periodicals, Inc.

Pituitary and ovarian abnormalities demonstrated by CT and ultrasound in children with features of the McCune-Albright syndrome

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

Rieth, K.G.; Comite, F.; Shawker, T.H.

1984-11-01

In a random series of 97 children referred to the National Institutes of Health with a presumptive diagnosis of precocious puberty, eight girls were found to have features of the McCune-Albright syndrome, including fibrous dysplasia of bone and/or skin lesions resembling cafe au lait spots. Radiographic evaluation of these patients included computed tomography of the head and pelvic ultrasound. The pituitary glands were suspicious for abnormality in five of the eight girls. Seven girls underwent pelvic ultrasound, and in all of them the ovaries were considered to be abnormal for their chronological age; in addition, two had functional ovarian cysts.more » The role of diagnostic radiological studies in the diagnosis of this syndrome is discussed.« less

Clinical features of congenital adrenal insufficiency including growth patterns and significance of ACTH stimulation test.

PubMed

Koh, Ji Won; Kim, Gu Hwan; Yoo, Han Wook; Yu, Jeesuk

2013-11-01

Congenital adrenal insufficiency is caused by specific genetic mutations. Early suspicion and definite diagnosis are crucial because the disease can precipitate a life-threatening hypovolemic shock without prompt treatment. This study was designed to understand the clinical manifestations including growth patterns and to find the usefulness of ACTH stimulation test. Sixteen patients with confirmed genotyping were subdivided into three groups according to the genetic study results: congenital adrenal hyperplasia due to 21-hydroxylase deficiency (CAH, n=11), congenital lipoid adrenal hyperplasia (n=3) and X-linked adrenal hypoplasia congenita (n=2). Bone age advancement was prominent in patients with CAH especially after 60 months of chronologic age (n=6, 67%). They were diagnosed in older ages in group with bone age advancement (P<0.05). Comorbid conditions such as obesity, mental retardation, and central precocious puberty were also prominent in this group. In conclusion, this study showed the importance of understanding the clinical symptoms as well as genetic analysis for early diagnosis and management of congenital adrenal insufficiency. ACTH stimulation test played an important role to support the diagnosis and serum 17-hydroxyprogesterone levels were significantly elevated in all of the CAH patients. The test will be important for monitoring growth and puberty during follow up of patients with congenital adrenal insufficiency.

Neoplastic causes of abnormal puberty.

PubMed

Wendt, Susanne; Shelso, John; Wright, Karen; Furman, Wayne

2014-04-01

Neoplasm-related precocious puberty (PP) is a rare presenting feature of childhood cancer. Moreover, evaluation of suspected PP in a child is complex, and cancer is often not considered. We characterized the clinicopathologic features of patients presenting with PP at a large pediatric cancer center, reviewed the relevant literature, and developed an algorithm for the diagnostic work-up of these patients. We examined the records of all patients with a neoplasm and concomitant PP treated at St. Jude Children's Research Hospital from January 1975 through October 2011, reviewed the available literature, and analyzed the demographic, clinical, endocrine, and neoplasm-related features. Twenty-four of 13,615 children and adolescents (0.18%) were diagnosed with PP within 60 days of presentation. Primary diagnoses included brain tumor (12), adrenocortical carcinoma (5), hepatoblastoma (4), and others (3). PP was observed 0-48 months before diagnosis of neoplasm; 17 patients had peripheral PP and 7 had central PP. Neoplasm-related PP is rare and takes the form of a paraneoplastic syndrome caused by tumor production of hormones or by alteration of physiologic gonadotropin production. PP can precede diagnosis of malignancy by months or years, and neoplastic causes should be considered early to avoid delayed cancer diagnosis. Treatment of the primary malignancy resolved or diminished PP in surviving patients with an intact hypothalamic-pituitary-gonadal axis. © 2013 Wiley Periodicals, Inc.

Long-term outcomes of letrozole treatment for precocious puberty in girls with McCune-Albright syndrome.

PubMed

Estrada, Andrea; Boyce, Alison M; Brillante, Beth A; Guthrie, Lori C; Gafni, Rachel I; Collins, Michael T

2016-11-01

McCune-Albright syndrome (MAS) is a rare disorder with a broad spectrum including precocious puberty (PP) due to recurrent estrogen-secreting ovarian cysts. This study evaluates the long-term safety and efficacy of letrozole treatment in large cohort of girls with MAS-associated PP. Retrospective cohort analysis. Clinical data, including history and physical examination, bone age, and pelvic ultrasounds, were reviewed on 28 letrozole-treated girls. Adult height was reviewed for 42 historical controls. Outcomes included rate of skeletal maturation, growth velocity, predicted adult height and adult height. Twenty-eight girls received letrozole treatment. Treatment duration was 4.1 ± 2.6 years (mean ± 1 s.d.) (range: 0.5-10.9) and mean follow-up was 6.0 ± 3.3 years (range: 0.5-15.0), for a total of 135.9 person-years of follow-up. Letrozole treatment was highly effective at decreasing the rate of skeletal maturation, with a decline in change in bone age over change in chronological age (ΔBA/ΔCA) from 1.7 (IQR: 2.3) to 0.5 (IQR: 0.4) (P < 0.0001), and growth velocity Z-scores, which declined from 2.2 ± 2.3 to -0.6 ± 1.6 (P = 0.0004). Predicted adult height Z-scores increased significantly from -2.9 ± 3.2 to -0.8 ± 1.5 for subjects on treatment (P = 0.004). Four subjects who completed treatment reached adult height Z-scores ranging from -1.5 to 1.7 (median: -0.6), which were increased in comparison with untreated historical controls (P = 0.02). There was no change in uterine size or ovarian volumes, and no adverse events over the treatment period. In this study with the longest follow-up to date, letrozole treatment resulted in sustained beneficial effects on skeletal maturation, growth velocity and predicted adult height. © 2016 European Society of Endocrinology.

Sex 'n' drugs 'n' rock 'n' roll: the meaning and social consequences of pubertal timing.

PubMed

Waylen, Andrea; Wolke, Dieter

2004-11-01

This is a brief review of the normal changes in adolescent behaviour and the interplay between biology and social factors that occur at and around puberty, in an attempt to explain when this transition may become problematic The onset of puberty is a biological marker for an individual's transition from a non-reproductive to a reproductive state. Adolescence is a normal developmental transition associated with clearly visible physical changes, reorganization and pruning of neuronal circuits in the brain and the occurrence of new behaviours and interests. It is a time when new life tasks (orientation towards peers of the other sex, romantic and sexual involvement and mastering an educational career) need to be mastered. Parent-child conflict increases and becomes more intense as the adolescent struggles for more independence while still requiring support. These normal changes can become problematic if biological and social expectations diverge e.g. entering puberty very early or very late. While early pubertal onset in boys is likely to have beneficial effects, in girls precocious pubertal timing may have a negative impact on body-image, affect (or emotional well-being) and sex-role expectations. Other individual biological predispositions and genetic endowment may interact with social factors (e.g. peers, parenting style, neighbourhood) making adolescence either an adaptive or a challenging transition. There is a lack of sufficiently large longitudinal studies that have been able to study this interaction between genetics, biology and social environment on adolescent development. The Avon Longitudinal Study of Parents and Children (ALSPAC) cohort provides a unique opportunity to investigate the impact of pubertal timing on social behaviour. Planned assessments and concepts are outlined.

Integrative testis transcriptome analysis reveals differentially expressed miRNAs and their mRNA targets during early puberty in Atlantic salmon.

PubMed

Skaftnesmo, K O; Edvardsen, R B; Furmanek, T; Crespo, D; Andersson, E; Kleppe, L; Taranger, G L; Bogerd, J; Schulz, R W; Wargelius, A

2017-10-18

Our understanding of the molecular mechanisms implementing pubertal maturation of the testis in vertebrates is incomplete. This topic is relevant in Atlantic salmon aquaculture, since precocious male puberty negatively impacts animal welfare and growth. We hypothesize that certain miRNAs modulate mRNAs relevant for the initiation of puberty. To explore which miRNAs regulate mRNAs during initiation of puberty in salmon, we performed an integrated transcriptome analysis (miRNA and mRNA-seq) of salmon testis at three stages of development: an immature, long-term quiescent stage, a prepubertal stage just before, and a pubertal stage just after the onset of single cell proliferation activity in the testis. Differentially expressed miRNAs clustered into 5 distinct expression profiles related to the immature, prepubertal and pubertal salmon testis. Potential mRNA targets of these miRNAs were predicted with miRmap and filtered for mRNAs displaying negatively correlated expression patterns. In summary, this analysis revealed miRNAs previously known to be regulated in immature vertebrate testis (miR-101, miR-137, miR-92b, miR-18a, miR-20a), but also miRNAs first reported here as regulated in the testis (miR-new289, miR-30c, miR-724, miR-26b, miR-new271, miR-217, miR-216a, miR-135a, miR-new194 and the novel predicted n268). By KEGG enrichment analysis, progesterone signaling and cell cycle pathway genes were found regulated by these differentially expressed miRNAs. During the transition into puberty we found differential expression of miRNAs previously associated (let7a/b/c), or newly associated (miR-15c, miR-2184, miR-145 and the novel predicted n7a and b) with this stage. KEGG enrichment analysis revealed that mRNAs of the Wnt, Hedgehog and Apelin signaling pathways were potential regulated targets during the transition into puberty. Likewise, several regulated miRNAs in the pubertal stage had earlier been associated (miR-20a, miR-25, miR-181a, miR-202, let7c/d/a, miR-125b, miR-222a/b, miR-190a) or have now been found connected (miR-2188, miR-144, miR-731, miR-8157 and the novel n2) to the initiation of puberty. This study has - for the first time - linked testis maturation to specific miRNAs and their inversely correlated expressed targets in Atlantic salmon. The study indicates a broad functional conservation of already known miRNAs and associated pathways involved in the transition into puberty in vertebrates. The analysis also reveals miRNAs not previously associated with testis tissue or its maturation, which calls for further functional studies in the testis.

Hyperandrogenemia in male autistic children and adolescents: relation to disease severity.

PubMed

El-Baz, Farida; Hamza, Rasha T; Ayad, Mohamed S E; Mahmoud, Nermine H

2014-01-01

It has been suggested that autistic patients have elevated blood androgens, and although signs of precocious puberty have been reported in autistic patients, such a relation has not yet been clarified. To assess serum androgen levels in a group of Egyptian male autistic children and adolescents and their relation to disease severity. In addition, the risk for association of androgens with autism was estimated. In comparison to 20 controls, 30 male autistic children were studied. All subjects were subjected to clinical evaluation, intelligence quotient (IQ) assessment and measurement of serum free testosterone (FT), dehydroepiandosterone (DHEA) and Δ4-androstenedione (Δ4-A). Androgens were higher in autistic patients than in controls and increased with increased autistic severity. Of the patients, 11 (36.66%) had high FT, 9 (30%) had high DHEA, 12 (40%) had high Δ4-A and 8 (26.66%) showed elevation of all androgen levels. 38.45, 95% CI: 2.14-688.93, p=0.013) and Δ4-A (OR: 13.6, 95%CI: 2.25-22.89, p=0.04) had a significant risk for association with autism. Hyperandrogenemia is prevalent in autistic patients and increases with autistic severity. Thus, androgen levels should be assessed in autistic patients with signs of early puberty. Further studies are warranted regarding trials of anti-androgen therapy in such patients.

Polish Society of Endocrinology Position statement on endocrine disrupting chemicals (EDCs).

PubMed

Rutkowska, Aleksandra; Rachoń, Dominik; Milewicz, Andrzej; Ruchała, Marek; Bolanowski, Marek; Jędrzejuk, Diana; Bednarczuk, Tomasz; Górska, Maria; Hubalewska-Dydejczyk, Alicja; Kos-Kudła, Beata; Lewiński, Andrzej; Zgliczyński, Wojciech

2015-01-01

With the reference to the position statements of the Endocrine Society, the Paediatric Endocrine Society, and the European Society of Paediatric Endocrinology, the Polish Society of Endocrinology points out the adverse health effects caused by endocrine disrupting chemicals (EDCs) commonly used in daily life as components of plastics, food containers, pharmaceuticals, and cosmetics. The statement is based on the alarming data about the increase of the prevalence of many endocrine disorders such as: cryptorchidism, precocious puberty in girls and boys, and hormone-dependent cancers (endometrium, breast, prostate). In our opinion, it is of human benefit to conduct epidemiological studies that will enable the estimation of the risk factors of exposure to EDCs and the probability of endocrine disorders. Increasing consumerism and the industrial boom has led to severe pollution of the environment with a corresponding negative impact on human health; thus, there is great necessity for the biomonitoring of EDCs in Poland.

Somatic and germinal cells' interrelationship in the course of seminiferous tubule maturation in man.

PubMed

Kula, K; Romer, T E; Wlodarczyk, W P

1980-02-01

Certain successive phases of seminiferous tubule maturation were observed in a transsection of a Leydig cell adenoma-bearing testis of a boy with precocious puberty. Massively accumulated Leydig cells may stimulate the maturation of Sertoli cells, as indicated by progressive replacement of Sertoli cell precursors by mature Sertoli cells at a distance closer to the adenoma. On the other hand, tubules less advanced in maturation contained a higher number of somatic cells than those more advanced in maturation. Leydig-cell-dependent maturation of Sertoli cells may be in competition with Certoli cell multiplication, or numerous undifferentiated somatic cells may undergo a natural elimination in the course of tubular maturation. An inverse relation between the number of Sertoli cell precursors and the number of meiotic spermatocytes suggests that quantitative reduction of Sertoli cell precursors may be important for the intratubular milieu necessary for the onset of the first meiosis in man.

Long term ocular and neurological involvement in severe congenital toxoplasmosis.

PubMed

Meenken, C; Assies, J; van Nieuwenhuizen, O; Holwerda-van der Maat, W G; van Schooneveld, M J; Delleman, W J; Kinds, G; Rothova, A

1995-06-01

This study was set up to determine the long term ocular and systemic sequelae in patients with severe congenital toxoplasmosis. Cross sectional and retrospective study of 17 patients with severe congenital toxoplasmosis. In addition to chorioretinitis (100%), the most common abnormal ocular features were optic nerve atrophy (83%), visual acuity of less than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed iridic abnormalities and about 40% developed a cataract. Overt endocrinological disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2), gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1). The observed endocrinological involvement was associated in all cases with obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy. The recognition of long term ocular, neurological, and endocrinological sequelae of congenital toxoplasmosis is important for medical management of these severely handicapped patients.

Triptorelin embonate: a 6-month formulation for prostate cancer.

PubMed

Whelan, Peter

2010-12-01

Luteinizing hormone releasing hormone (LH RH) agonists are the major agent for androgen deprivation therapy in advanced and metastatic prostate cancer. They also have a role in endometriosis, uterine fibroids and central precocious puberty. Triptorelin embonate 22.5 mg is a new, sustained-release, 6-month formulation of an LH RH agonist. It possesses longer duration of action than the current standard 3-month preparation and appears to have similar efficacy and side effects. The use of LH RH agonists for androgen deprivation in prostate cancer has increased considerably in the last 20 years. Recent work has shown that some of this usage has constituted overtreatment and it is within these newer paradigms of therapy that the new 6-month preparation is situated. The new 6-month LH RH preparation - triptorelin embonate - will be of help in several key areas of therapy for prostate cancer, notably as an adjunct to radiation therapy and chemotherapy. It possesses a similar effect, but with fewer side effects, than those that are now commonly available.

Seizures presenting as incessant laughter: a case of gelastic epilepsy.

PubMed

Holmes, Christina M; Goldman, Mitchell J

2012-12-01

Gelastic seizures are defined as seizure activity manifesting as laughter inappropriate to the situation, with supporting evidence on electroencephalogram or magnetic resonance imaging. Gelastic seizures are most commonly reported in patients with hypothalamic hamartomas causing precocious puberty. The differential diagnosis of incessant laughter is important to recognize in the Emergency Department, as some conditions warrant immediate treatment and others require further diagnostic work-up with implications for the entire family. The background and pathophysiology of gelastic epilepsy will be discussed. The case of a previously healthy girl with acute onset of incessant laughter is reported. This patient was diagnosed with a clinical case of gelastic seizures. This case illustrates the importance of recognizing this form of seizures for accurate treatment and follow-up. This case report illustrates the importance of a broad differential for a patient presenting emergently with uncontrollable laughter. Gelastic epilepsy is relatively rare but requires further work-up and often may require chronic therapy. Copyright © 2012 Elsevier Inc. All rights reserved.

Gigantism due to growth hormone excess in a boy with optic glioma.

PubMed

Drimmie, F M; MacLennan, A C; Nicoll, J A; Simpson, E; McNeill, E; Donaldson, M D

2000-10-01

True gigantism is rare in early childhood and is usually due to excess GH secretion from a pituitary adenoma. We report a case in which the endocrine abnormality is secondary to an optic glioma. Careful endocrine evaluation has shown that GH peak amplitude was not increased but rather there was failure of GH levels to suppress to baseline and a lack of pulsatility. There is no evidence of a direct secretory role for the tumour and we postulate that the tumour is affecting GH secretion through an effect on somatostatin tone. Specific tumour therapy is not indicated for this patient in the absence of mass effect or visual disturbance. The GH excess is being treated with somatostatin analogue (Octreotide) and as he has developed precocious puberty he is also receiving long acting GnRH analogue (Zoladex). This boy appears likely to have neurofibromatosis type 1 (NF1) which raises the question of subtle GH excess in NF1 patients with tall stature.

Mazabraud syndrome associated with McCune-Albright syndrome: a case report and review of the literature.

PubMed

Biazzo, Alessio; Di Bernardo, Andrea; Parafioriti, Antonina; Confalonieri, Norberto

2017-08-23

Mazabraud syndrome is a very rare benign disorder characterized by the association of monostotic or polyostotic fibrous dysplasia and one or multiple intramuscular myxomas. McCune -Albright syndrome is a rare benign disorder characterized by the association of polyostotic fibrous dysplasia, cafè-au-lait skin pigmentations and endocrine dysfunction, such as precocious puberty, diabetes mellitus, goiter and breast fibroadenomatosis. The association of Mazabraud syndrome and McCune-Albright in the same patient is an anecdotal event. We report the case of a 28-year-old girl with Mazabraud syndrome associated with McCune-Albright syndrome. Our literature review shows that in these patients there is a higher risk of malignant transformation of fibrous dysplasia into osteosarcoma, confirming previous reports. Conversely, no malignant transformation has been reported for myxomas in isolated Mazabraud syndrome or in the association with McCune-Albright syndrome. We conclude that these patients should be scheduled to a close and long-term follow-up.

Long term ocular and neurological involvement in severe congenital toxoplasmosis.

PubMed Central

Meenken, C; Assies, J; van Nieuwenhuizen, O; Holwerda-van der Maat, W G; van Schooneveld, M J; Delleman, W J; Kinds, G; Rothova, A

1995-01-01

AIMS--This study was set up to determine the long term ocular and systemic sequelae in patients with severe congenital toxoplasmosis. METHODS--Cross sectional and retrospective study of 17 patients with severe congenital toxoplasmosis. RESULTS--In addition to chorioretinitis (100%), the most common abnormal ocular features were optic nerve atrophy (83%), visual acuity of less than 0.1 (85%), strabismus, and microphthalmos. In 50% of cases we observed iridic abnormalities and about 40% developed a cataract. Overt endocrinological disease, diagnosed in five of 15 patients, included panhypopituitarism (n = 2), gonadal failure with dwarfism (n = 1), precocious puberty with dwarfism and thyroid deficiency (n = 1), and diabetes mellitus and thyroid deficiency (n = 1). The observed endocrinological involvement was associated in all cases with obstructive hydrocephalus with a dilated third ventricle and optic nerve atrophy. CONCLUSION--The recognition of long term ocular, neurological, and endocrinological sequelae of congenital toxoplasmosis is important for medical management of these severely handicapped patients. PMID:7626575

Prevalence and risk factors for type 2 diabetes mellitus with Prader-Willi syndrome: a single center experience.

PubMed

Yang, Aram; Kim, Jinsup; Cho, Sung Yoon; Jin, Dong-Kyu

2017-08-30

Prader-Willi syndrome (PWS) is often related to severe obesity and type-2 diabetes mellitus (T2DM). However, few studies, and none in Korea, have examined prevalence of T2DM and other variables in PWS. The aim of this study was to identify the prevalence and associated risk factors for T2DM in Korean patients with PWS. We performed a retrospective cohort study of the 84 PWS patients aged 10 or over (10.3-35.8 years of age) diagnosed with PWS at Samsung Medical Center from 1994 to 2016. We estimated occurrence of T2DM according to age (10-18 years versus >18 years), body mass index (BMI), genotype, history of growth hormone therapy, homeostasis model of assessment-insulin resistance (HOMA-IR), and the presence of dyslipidemia, hypogonadism, or central precocious puberty. Additionally, we investigated cutoff values of risk factors for development of T2DM. Twenty-nine of a total 211 patients, diagnosed with PWS over the study period, were diagnosed as having T2DM (13.7%, mean age 15.9 ± 3.6 years). In the >18 years group, obesity, HOMA-IR, and presence of dyslipidemia, hypogonadism, or central precocious puberty were associated with the occurrence of T2DM in univariate analysis. In multivariate logistic regression analysis, only obesity (p = 0.001) and HOMA-IR (p < 0.001) were significant predictive factors for T2DM. Based on the receiver operating a characteristic curve analysis, the cutoff values of HOMA-IR and BMI for predicting T2DM were >2.7 and >28.49 kg/m 2 , respectively. Of the 29 patients, seven had ≥1 microvascular complication, with non-proliferative diabetic retinopathy in 6 of 7 cases. Advanced age and HOMA-IR were positively correlated with diabetic microvascular complications (p < 0.05, Spearman correlation coefficient 0.393 and 0.434, respectively). The prevalence of diabetes in Korean PWS was similar to that in previous results. BMI and HOMA-IR were strong predictive factors for the development of T2DM in PWS. We specifically suggest the regular monitoring of glucose homeostasis parameters through a detailed settlement of ethnically specific cutoff values for BMI and HOMA-IR in PWS to prevent progression of T2DM and diabetic microvascular complications.

A child with hypertension and ambiguous genitalia - an uncommon variant of congenital adrenal hyperplasia: a case report.

PubMed

Pant, Vivek; Baral, Suman; Shrestha, Bishal; Tumbapo, Arjun

2017-06-23

Deficiency in 11β-hydroxylase as a cause of congenital adrenal hyperplasia is uncommon. It should be considered in the differential diagnosis of hypertension with virilization in any prepubescent child. A 12-year-old Asian boy from eastern Nepal presented with pain in his abdomen and hypertension. He was raised as a male but had absent testicles since birth and had precocious puberty. Plasma testosterone, follicle-stimulating hormone, and luteinizing hormone were below baseline level. Basal 17-hydroxyprogesterone was elevated. Magnetic resonance imaging of his pelvis showed presence of Müllerian structures and karyotyping revealed 46,XX genotype. A clinical diagnosis of 11β-hydroxylase deficiency was made in view of hypertension with severe virilization in a 46,XX individual. Our patient's legal guardian was unwilling for our patient to change gender and because our patient is underage, the condition was well explained to his parents. He was managed with steroids and antihypertensive drugs. He was on regular follow-up; after 2 years there was no hypertension but he developed true puberty with functional ovaries. He was prescribed leuprolide (gonadotropin-releasing hormone analogue), letrozole (aromatase inhibitor), and a continuation of antihypertensive drugs. This case highlights the importance of a thorough physical examination of the external genitalia at birth and appropriate referral, and addresses issues in the management of such a disorder. Ethical issues pertaining to consent and who is entitled to give it should be clear so that the affected individual will have optimal psychological development and quality of life.

Early metformin therapy (age 8-12 years) in girls with precocious pubarche to reduce hirsutism, androgen excess, and oligomenorrhea in adolescence.

PubMed

Ibáñez, Lourdes; López-Bermejo, Abel; Díaz, Marta; Marcos, Maria Victoria; de Zegher, Francis

2011-08-01

Girls with a combined history of low(-normal) birth weight (LBW) and precocious pubarche (PP) are at high risk to develop polycystic ovary syndrome (PCOS). The objective of the study was to compare the capacity of early vs. late metformin treatment to prevent adolescent PCOS. This was a randomized, open-label study over 7 yr. The study was conducted at a university hospital. Thirty-eight LBW-PP girls were followed up from the mean age 8 until age 15 yr. Early metformin (study yr 1-4; age 8-12 yr) vs. late metformin (yr 6; age 13-14 yr). Measures included height; weight; hirsutism score; menstrual cycle; endocrine-metabolic screening (fasting; follicular phase); C-reactive protein; body composition (absorptiometry); abdominal fat partitioning (magnetic resonance imaging); ovarian morphology (ultrasound); PCOS (National Institutes of Health and Androgen Excess Society definitions) after yr 7 (all girls thus untreated for at least 1 yr). None of the girls dropped out of the study. At age 15 yr, early-metformin girls were taller (4 cm), were in a less proinflammatory state, and had less central fat due to reductions in visceral and hepatic fat. Hirsutism, androgen excess, oligomenorrhea, and PCOS were between 2- and 8-fold more prevalent in late- than early-treated girls. Abdominal adiposity was the first variable to diverge (at age 8-10 yr) between girls without vs. with PCOS at age 15 yr. In LBW-PP girls, early metformin therapy was found to prevent or delay the development of hirsutism, androgen excess, oligomenorrhea, and PCOS more effectively than late metformin. The time window of late childhood and early puberty may be more critical for the development, and thus for the prevention, of adolescent PCOS than the first years beyond menarche.

A noninvasive estimation of cerebral perfusion pressure using critical closing pressure.

PubMed

Varsos, Georgios V; Kolias, Angelos G; Smielewski, Peter; Brady, Ken M; Varsos, Vassilis G; Hutchinson, Peter J; Pickard, John D; Czosnyka, Marek

2015-09-01

Cerebral blood flow is associated with cerebral perfusion pressure (CPP), which is clinically monitored through arterial blood pressure (ABP) and invasive measurements of intracranial pressure (ICP). Based on critical closing pressure (CrCP), the authors introduce a novel method for a noninvasive estimator of CPP (eCPP). Data from 280 head-injured patients with ABP, ICP, and transcranial Doppler ultrasonography measurements were retrospectively examined. CrCP was calculated with a noninvasive version of the cerebrovascular impedance method. The eCPP was refined with a predictive regression model of CrCP-based estimation of ICP from known ICP using data from 232 patients, and validated with data from the remaining 48 patients. Cohort analysis showed eCPP to be correlated with measured CPP (R = 0.851, p < 0.001), with a mean ± SD difference of 4.02 ± 6.01 mm Hg, and 83.3% of the cases with an estimation error below 10 mm Hg. eCPP accurately predicted low CPP (< 70 mm Hg) with an area under the curve of 0.913 (95% CI 0.883-0.944). When each recording session of a patient was assessed individually, eCPP could predict CPP with a 95% CI of the SD for estimating CPP between multiple recording sessions of 1.89-5.01 mm Hg. Overall, CrCP-based eCPP was strongly correlated with invasive CPP, with sensitivity and specificity for detection of low CPP that show promise for clinical use.

Select corn coproducts from the ethanol industry and their potential as ingredients in pet foods.

PubMed

de Godoy, M R C; Bauer, L L; Parsons, C M; Fahey, G C

2009-01-01

The objectives of this study were to determine the chemical composition and nutritive value of corn protein product 1 (CPP 1), corn protein product 2 (CPP 2), and corn fiber (CF), novel coproducts of the ethanol industry, and compare these feed ingredients with standard plant protein ingredients [soybean meal (SBM), distillers dried grains with solubles (DDGS), corn gluten meal (CGlM), and corn germ meal (CGeM)], and to compare CF sources (CF control 1 and control 2) with standard fiber sources (peanut hulls, Solka-Floc, and beet pulp) commonly used in pet foods. Corn fiber, CPP 1, and CPP 2 were produced at a pilot-scale modified dry-grind plant, with CPP 2 having a greater degree of purification than CPP 1. Crude protein values for CPP 2 and CPP 1 were 57.3 and 49.7%, respectively. Total dietary fiber concentration was 29% for CPP 2 and 23.5% for CPP 1. Acid-hydrolyzed fat and GE concentrations were similar for these ingredients. In a protein efficiency ratio assay, no differences (P > 0.05) in feed intake, BW gain, or CP intake were noted for CPP 2, CPP 1, or CGlM. However, feeding CPP 2 resulted in a greater (P < 0.05) G:F ratio and protein efficiency ratio than CPP 1 and CGlM. In a cecectomized rooster assay, CGlM had numerically the greatest standardized total AA, total essential AA, and total nonessential AA digestibilities, but they were not different (P > 0.05) from CPP 1 or SBM values. Corn germ meal resulted in the least values, but they were not different from those for DDGS and CPP 1. The greatest values for true nitrogen-corrected ME were obtained with CGlM, followed by CPP 2, DDGS, CPP 1, SBM, and CGeM. Distillers dried grains with solubles and CPP 1 had similar true nitrogen-corrected ME values, and they were not different from values for CPP 2 and SBM. In vitro CP disappearance was greatest (P < 0.05) for CGlM (94.1%), intermediate for DDGS (76.8%) and CPP 1 (77.5%), and least for CPP 2 (74.1%) and CGeM (67.7%). Corn fibers contained predominantly insoluble dietary fiber (1% or less of soluble dietary fiber), with a moderate CP concentration. In vitro OM disappearance for the fiber sources, when using inoculum from dog feces, revealed that with the exception of beet pulp, which had a moderate disappearance value after 16 h of fermentation (17.7%), all fiber substrates had a nonsignificant extent of fermentation. In conclusion, novel corn coproducts had properties comparable with the standard protein and fiber sources used in animal nutrition.

Ultrasound-responsive nanobubbles contained with peptide-camptothecin conjugates for targeted drug delivery.

PubMed

Xie, Xiangyang; Lin, Wen; Liu, Hui; Deng, Jianping; Chen, Ying; Liu, Hong; Fu, Xudong; Yang, Yang

2016-10-01

To improve the targeting delivery efficiency of anticancer drug to tumor sites, a new strategy combining cell-permeable peptide (CPP) and ultrasound was reported in this article. In this study, we devised and tested a strategy for functional payload delivery to cells by loading CPP-camptothecin conjugate (CPP-CPT) into nanobubble (CPP-CPT NB). Here, CPP existing in the conjugation form of CPP and CPT was hidden in nanobubble to cloak the penetration activity of CPP. Meanwhile, local tumor ultrasound was utilized to achieve specific targeting of CPP-CPT to the tumor cells. The mean particle size of the prepared CPP-CPT NB was ∼200 nm, and the drug entrapment efficiency was >80%. Stimulated by ultrasound, over 90% of the entrapped CPP-CPTs would release from the nanobubbles. Subsequent research demonstrated that the CPP-CPT NB showed effective cellular uptake and significant cytotoxic activity in HeLa cells in vitro. Additionally, after systemic administration in mice, CPP-CPT NB with ultrasound showed a higher tumor inhibition effect in nude mice xenografted HeLa cells tumors and excellent body safety when compared with normal CPT injection group. In conclusion, the carrier constructed in this study would be a safe and efficiently drug delivery system for specific cancer treatment.

Learning from bottom-up dissemination: Importing an evidence-based trauma intervention for infants and young children to Israel.

PubMed

David, Paula; Schiff, Miriam

2015-12-01

This article describes a pilot study of a "bottom up" dissemination process of a new evidence based intervention for treating early childhood trauma. Clinicians applied to learn Child-Parent Psychotherapy (CPP), imported to Israel from the U.S. A focus group of six graduates of a CPP training program responded to questions concerning their experiences learning and using CPP. All 39 CPP graduates from two cohorts also completed a cross sectional survey related to their use of CPP. Within the focus group, the openness of the workplace and the intervention's characteristics were considered major factors impacting CPP use; the training program was perceived to promote CPP implementation, and lack of supervision and secondary traumatic stress were the major inhibiting factors. Using CPP-informed therapy, as opposed to CPP with fidelity, was perceived to be one of the main outcomes of the training. Survey results showed that 53% of graduates were using CPP in over three cases, and almost all intended to use CPP within the next year. Ninety-five percent were using CPP principles in their therapeutic work. The implications of importing a new evidence based intervention to a foreign country that utilizes a different dissemination system within a different professional culture are discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss.

PubMed

Alencar, Catarina Ribeiro Barros de; Oliveira, Gabriela Cristina de; Magalhães, Ana Carolina; Buzalaf, Marília Afonso Rabelo; Machado, Maria Aparecida de Andrade Moreira; Honório, Heitor Marques; Rios, Daniela

2017-01-01

This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI - Sugar free chewing gum with CPP-ACP; GII - Conventional sugar free chewing gum; and GIII - No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey's test (p<0.05). The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss.

Efficacy of pastes containing CPP-ACP and CPP-ACFP in patients with Sjögren's syndrome.

PubMed

Peric, Tamara; Markovic, Dejan; Petrovic, Bojan; Radojevic, Vesna; Todorovic, Tatjana; Radicevic, Biljana Andjelski; Heinemann, Radmila Jancic; Susic, Gordana; Popadic, Aleksandra Peric; Spiric, Vesna Tomic

2015-12-01

The purpose of this study was to evaluate efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) containing pastes among individuals with Sjögren's syndrome (SS). Thirty patients were randomised into three groups: CPP-ACP, CPP-ACFP, and 0.05 % NaF to be used two times a day during a 28-day experimental period. Saliva was analysed for flow rate, pH, buffering capacity and mineral concentrations. Dental plaque was examined for pH. Following the formation of artificial carious lesion, participants wore enamel slabs for an in situ remineralisation study. Remineralisation potential was examined using scanning electron microscope (SEM) and energy dispersive spectroscopic (EDS) technique. SE microphotographs were subsequently analysed for area, diameter, perimeter, roundness and the number of enamel defects and percentage of tooth surface affected by defects. At the end of the experimental period, a slight increase of salivary pH could have been observed. No differences in mineral composition of saliva were noted. The use of CPP-ACP and CPP-ACFP contributed to a significant rise of plaque pH. Image analysis revealed excessive reduction of defects' dimensions in the three experimental groups, and a decrease of the number of enamel defects in the CPP-ACP and CPP-ACFP groups. The EDS analysis did not show differences in Ca/P, Ca/O and P/O ratios in any of the treatment groups. CPP-ACP and CPP-ACFP hold promise as remineralising agents for patients with SS. Pastes containing CPP-ACP/CPP-ACFP show enhanced remineralisation potential compared with NaF mouthrinse in patients with SS.

In situ effect of CPP-ACP chewing gum upon erosive enamel loss

PubMed Central

de ALENCAR, Catarina Ribeiro Barros; de OLIVEIRA, Gabriela Cristina; MAGALHÃES, Ana Carolina; BUZALAF, Marília Afonso Rabelo; MACHADO, Maria Aparecida de Andrade Moreira; HONÓRIO, Heitor Marques; RIOS, Daniela

2017-01-01

Abstract Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is able to increase salivary calcium and phosphate levels at an acidic pH. Previous studies demonstrated that a CPP-ACP chewing gum was able to enhance the re-hardening of erosion lesions, but could not diminish enamel hardness loss. Therefore, there is no consensus regarding the effectiveness of CPP-ACP on dental erosion. Objective This in situ study investigated the ability of a CPP-ACP chewing gum in preventing erosive enamel loss. Material and Methods: During three experimental crossover phases (one phase per group) of seven days each, eight volunteers wore palatal devices with human enamel blocks. The groups were: GI – Sugar free chewing gum with CPP-ACP; GII – Conventional sugar free chewing gum; and GIII – No chewing gum (control). Erosive challenge was extraorally performed by immersion of the enamel blocks in cola drink (5 min, 4x/day). After each challenge, in groups CPP and No CPP, volunteers chewed one unit of the corresponding chewing gum for 30 minutes. Quantitative analysis of enamel loss was performed by profilometry (µm). Data were analyzed by Repeated-Measures ANOVA and Tukey’s test (p<0.05). Results The use of chewing gum (CPP and No CPP) resulted in lower erosive enamel loss compared with the control group (p<0.05). CPP-ACP chewing gum (CPP) did not improve the protection against erosive enamel loss compared with conventional chewing gum (No CPP) (p>0.05). Conclusion The CPP-ACP chewing gum was not able to enhance the anti-erosive effect of conventional chewing gum against enamel loss. PMID:28678944

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601), SECOND FLOOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601), SECOND FLOOR SHOWING PROCESS MAKEUP AREA AND EIGHTEEN CELLS AND ADJOINING REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING COLD LAB, DECONTAMINATION ROOM, MULTICURIE CELL ROOM, AND OFFICES. TO LEFT ARE LABORATORY BUILDING (CPP-602) AND MAINTENANCE BUILDING (CPP-630). INL DRAWING NUMBER 200-0601-00-706-051980. ALTERNATE ID NUMBER CPP-E-1980. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601), FIRST FLOOR SHOWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601), FIRST FLOOR SHOWING SAMPLE CORRIDORS AND EIGHTEEN CELLS AND ADJOINING REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING REMOTE ANALYTICAL FACILITIES LAB, DECONTAMINATION ROOM, AND MULTICURIE CELL ROOM. TO LEFT ARE LABORATORY BUILDING (CPP-602) AND MAINTENANCE BUILDING (CPP-630). INL DRAWING NUMBER 200-0601-00-706-051979. ALTERNATE ID NUMBER CPP-E-1979. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Effects of the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on mechanical properties of luting and lining glass ionomer cement

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-07-01

Recently, the addition of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into glass ionomer cements (GICs) has attracted interest due to its remineralization of teeth and its antibacterial effects. However, it should be investigated to ensure that the incorporation of CPP-ACP does not have significant adverse effects on its mechanical properties. The purpose of this study was to evaluate the effects of the addition of CPP-ACP on the mechanical properties of luting and lining GIC. The first step was to synthesize the CPP-ACP. Then the CPP-ACP at concentrations of 1%, 1.56% and 2% of CPP-ACP was added into a luting and lining GIC. GIC without CPP-ACP was used as a control group. The results revealed that the incorporation of CPP-ACP up to 1.56%(w/w) increased the flexural strength (29%), diametral tensile strength (36%) and microhardness (18%), followed by a reduction in these mechanical properties at 2%(w/w) CPP-ACP. The wear rate was significantly decreased (23%) in 1.56%(w/w) concentration of CPP-ACP and it was increased in 2%(w/w). Accordingly, the addition of 1.56%(w/w) CPP-ACP into luting and lining GIC had no adverse effect on the mechanical properties of luting and lining GIC and could be used in clinical practice.

A National Trial on Differences in Cerebral Perfusion Pressure Values by Measurement Location.

PubMed

McNett, Molly M; Bader, Mary Kay; Livesay, Sarah; Yeager, Susan; Moran, Cristina; Barnes, Arianna; Harrison, Kimberly R; Olson, DaiWai M

2018-04-01

Cerebral perfusion pressure (CPP) is a key parameter in management of brain injury with suspected impaired cerebral autoregulation. CPP is calculated by subtracting intracranial pressure (ICP) from mean arterial pressure (MAP). Despite consensus on importance of CPP monitoring, substantial variations exist on anatomical reference points used to measure arterial MAP when calculating CPP. This study aimed to identify differences in CPP values based on measurement location when using phlebostatic axis (PA) or tragus (Tg) as anatomical reference points. The secondary study aim was to determine impact of differences on patient outcomes at discharge. This was a prospective, repeated measures, multi-site national trial. Adult ICU patients with neurological injury necessitating ICP and CPP monitoring were consecutively enrolled from seven sites. Daily MAP/ICP/CPP values were gathered with the arterial transducer at the PA, followed by the Tg as anatomical reference points. A total of 136 subjects were enrolled, resulting in 324 paired observations. There were significant differences for CPP when comparing values obtained at PA and Tg reference points (p < 0.000). Differences remained significant in repeated measures model when controlling for clinical factors (mean CPP-PA = 80.77, mean CPP-Tg = 70.61, p < 0.000). When categorizing CPP as binary endpoint, 18.8% of values were identified as adequate with PA values, yet inadequate with CPP values measured at the Tg. Findings identify numerical differences for CPP based on anatomical reference location and highlight importance of a standard reference point for both clinical practice and future trials to limit practice variations and heterogeneity of findings.

Changes in regional gray matter volume in women with chronic pelvic pain - a voxel based morphometry study

PubMed Central

As-Sanie, Sawsan; Harris, Richard; Napadow, Vitaly; Kim, Jieun; Neshewat, Gina; Kairys, Anson; Williams, David; Clauw, Daniel; Schmidt-Wilcke, Tobias

2012-01-01

Chronic pelvic pain (CPP) is a highly prevalent pain condition, estimated to affect 15-20% of women in the United States. Endometriosis is often associated with CPP, however other factors, such as pre-existing or concomitant changes of the central pain system, might contribute to the development of chronic pain. We applied voxel-based morphometry to determine whether women with CPP with and without endometriosis display changes in brain morphology in regions known to be involved in pain processing.Four subgroups of women participated: 17 with endometriosis and CPP, 15 with endometriosis without CPP, 6 with CPP without endometriosis, as well as 23 healthy controls. All patients with endometriosis and/or CPP were surgically-confirmed. Relative to controls, women with endometriosis-associated CPP displayed decreased gray matter volume in brain regions involved in pain perception including the left thalamus, left cingulategyrus, right putamen, and right insula. Women with CPP without endometriosis also showed decreases in gray matter volume in the left thalamus. Such decreases were not observed in patients with endometriosis that had no CPP. We conclude thatCPP is associated with changes in regional gray matter volume within the central pain system. Although endometriosis may be an important risk factor for the development of CPP, acting as a cyclic source of peripheral nociceptive input, our data support the notion that changes in the central pain system also play an important role in the development of chronic pain, regardless of the presence of endometriosis. PMID:22387096

The effect of CPP-ACP-propolis chewing gum on calcium and phosphate ion release on caries-active subjects’ saliva and the formation of Streptococcus mutans biofilm

NASA Astrophysics Data System (ADS)

Hasnamudhia, F.; Bachtiar, E. W.; Sahlan, M.; Soekanto, S. A.

2017-08-01

The aim of this study was to analyze the effect of CPP-APP and propolis wax if they are combined in a chewing gum formulation, observed from the calcium and phosphate ion level released by CPP-ACP and the emphasis of Streptococcus mutans mass in the biofilm by propolis wax on caries-active subjects’ saliva. Chewing gum simulation was done in vitro on 25 caries-active subjects’ saliva using five concentrations of chewing gum (0% propolis + 0% CPP-ACP, 0% propolis + CPP-ACP, 2% propolis + CPP-ACP, 4% propolis + CPP-ACP, and 6% propolis + CPP-ACP) and was then tested using an atomic absorption spectrophotometer to analyze calcium ion levels, an ultraviolet-visible spectrophotometer to analyze phosphate ion levels, and a biofilm assay using crystal violet to analyze the decline in biofilm mass. After the chewing simulation, calcium ion levels on saliva+gum eluent increased significantly compared to the saliva control, with the highest calcium level released by CPP-ACP + 2% propolis chewing gum. There was an insignificant phosphate level change between the saliva control and saliva+gum eluent. There was also a significant decline of S. mutans biofilm mass in the saliva+gum eluent, mostly by the CPP-ACP chewing gum and CPP-ACP + 6% propolis. The CPP-ACP-propolis chewing gum simulation generated the largest increase in calcium and phosphate ion level and the largest decline in S. mutans biofilm mass.

Ovarian morphology and function during growth hormone therapy of short girls born small for gestational age.

PubMed

Tinggaard, Jeanette; Jensen, Rikke Beck; Sundberg, Karin; Birkebæk, Niels; Christiansen, Peter; Ellermann, Annie; Holm, Kirsten; Jeppesen, Eva Mosfeldt; Kremke, Britta; Marcinski, Pawel; Pedersen, Carsten; Saurbrey, Nina; Thisted, Ebbe; Main, Katharina M; Juul, Anders

2014-12-01

To study the effect of growth hormone (GH) treatment on ovarian and uterine morphology and function in short, prepubertal small-for-gestational-age (SGA) girls. A multinational, randomized controlled trial on safety and efficacy of GH therapy in short, prepubertal children born SGA. Not applicable. A subgroup of 18 Danish girls born SGA included in North European SGA Study (NESGAS). One year of GH treatment (67 μg/kg/day) followed by 2 years of randomized GH treatment (67 μg/kg/day, 35 μg/kg/day, or IGF-I titrated). Data on anthropometrics, reproductive hormones, and ultrasonographic examination of the internal genitalia were collected during 36 months of GH treatment. Uterine and ovarian volume increased significantly during 3 years of treatment (64% and 110%, respectively) but remained low within normal reference ranges. Ovarian follicles became visible in 58% after 1 year compared with 28% before GH therapy. Anti-Müllerian hormone increased significantly during the 3 years of GH therapy but remained within the normal range. Precocious puberty was observed in one girl; another girl developed multicystic ovaries. GH treatment was associated with statistically significant growth of the internal genitalia, but remained within the normal range. As altered pubertal development and ovarian morphology were found in 2 of 18 girls, monitoring of puberty and ovarian function during GH therapy in SGA girls is prudent. Altogether, the findings are reassuring. However, long-term effects of GH treatment on adult reproductive function remain unknown. EudraCT 2005-001507-19. Copyright © 2014 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

Genotype-phenotype characterization in 13 individuals with chromosome Xp11.22 duplications.

PubMed

Grams, Sarah E; Argiropoulos, Bob; Lines, Matthew; Chakraborty, Pranesh; Mcgowan-Jordan, Jean; Geraghty, Michael T; Tsang, Marilyn; Eswara, Marthand; Tezcan, Kamer; Adams, Kelly L; Linck, Leesa; Himes, Patricia; Kostiner, Dana; Zand, Dina J; Stalker, Heather; Driscoll, Daniel J; Huang, Taosheng; Rosenfeld, Jill A; Li, Xu; Chen, Emily

2016-04-01

We report 13 new individuals with duplications in Xp11.22-p11.23. The index family has one male and two female members in three generations with mild-severe intellectual disability (ID), speech delay, dysmorphic features, early puberty, constipation, and/or hand and foot abnormalities. Affected individuals were found to have two small duplications in Xp11.22 at nucleotide position (hg19) 50,112,063-50,456,458 bp (distal) and 53,160,114-53,713,154 bp (proximal). Collectively, these two regions include 14 RefSeq genes, prompting collection of a larger cohort of patients, in an attempt to delineate critical genes associated with the observed phenotype. In total, we have collected data on nine individuals with duplications overlapping the distal duplication region containing SHROOM4 and DGKK and eight individuals overlapping the proximal region including HUWE1. Duplications of HUWE1 have been previously associated with non-syndromic ID. Our data, with previously published reports, suggest that duplications involving SHROOM4 and DGKK may represent a new syndromic X-linked ID critical region associated with mild to severe ID, speech delay +/- dysarthria, attention deficit disorder, precocious puberty, constipation, and motor delay. We frequently observed foot abnormalities, 5th finger clinodactyly, tapering fingers, constipation, and exercise intolerance in patients with duplications of these two genes. Regarding duplications including the proximal region, our observations agree with previous studies, which have found associations with intellectual disability. In addition, expressive language delay, failure to thrive, motor delay, and 5th finger clinodactyly were also frequently observed in patients with the proximal duplication. © 2015 Wiley Periodicals, Inc.

Enhanced current-perpendicular-to-plane giant magnetoresistance effect in half-metallic NiMnSb based nanojunctions with multiple Ag spacers

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

Wen, Zhenchao; Yamamoto, Tatsuya; Kubota, Takahide

2016-06-06

Current-perpendicular-to-plane giant magnetoresistance (CPP-GMR) heterostructure devices using half-metallic NiMnSb Heusler alloy electrodes with single, dual, and triple Ag spacers were fabricated. The NiMnSb alloy films and Ag spacers show (001) epitaxial growth in all CPP-GMR multilayer structures. The dual-spacer CPP-GMR nanojunction exhibited an enhanced CPP-GMR ratio of 11% (a change in the resistance-area product, ΔRA, of 3.9 mΩ μm{sup 2}) at room temperature, which is approximately twice (thrice) of 6% (1.3 mΩ μm{sup 2}) in the single-spacer device. The enhancement of the CPP-GMR effects in the dual-spacer devices could be attributed to improved interfacial spin asymmetry. Moreover, it was observedmore » that the CPP-GMR ratios increased monotonically as the temperatures decreased. At 4.2 K, a CPP-GMR ratio of 41% (ΔRA = 10.5 mΩ μm{sup 2}) was achieved in the dual-spacer CPP-GMR device. This work indicates that multispacer structures provide an efficient enhancement of CPP-GMR effects in half-metallic material-based CPP-GMR systems.« less

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children

PubMed Central

Poureslami, H.; Hoseinifar, Ra.; Khazaeli, P.; Hoseinifar, Re.; Sharifi, H.; Poureslami, P.

2017-01-01

Statement of Problem: The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. Objectives: The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. Materials and Methods: One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Results: Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. Conclusions: CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene. PMID:28959766

Changes in the Concentration of Ions in Saliva and Dental Plaque after Application of CPP-ACP with and without Fluoride among 6-9 Year Old Children.

PubMed

Poureslami, H; Hoseinifar, Ra; Khazaeli, P; Hoseinifar, Re; Sharifi, H; Poureslami, P

2017-03-01

The casein phospho peptide-amorphous calcium phosphate with or without fluoride (CPP-ACPF and CPP-ACP respectively) are of considerably new materials which are highly recommended for prevention of dental caries. However, there is a shortage in literature on how they affect the ion concentration of saliva or dental plaque. The aim of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children with Early Childhood Caries (ECC) after applying the CPP-ACP paste in comparison with the use of CPP-ACPF paste. One ml of un-stimulated saliva of 25 preschool children was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. CPP-ACP as well as CPP-ACPF pastes were applied on the tooth surfaces in two separate steps. In steps, plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Atomic Absorption Device and the amount of phosphate and fluoride ions was measured by Ion Chromatography instrument. Data were analyzed using Repeated Measurements ANOVA at a p < 0.05 level of significance. Application of both CPP-ACPF and CPP-ACP significantly increased the concentration of calcium, phosphate, and fluoride in both saliva and dental plaque. Moreover, significantly higher salivary fluoride concentration was seen after application of CPP-ACPF compared to CPP-ACP. No other significant difference was observed between these two materials. CPP-ACPF can be more useful than CPP-ACP in protecting the primary teeth against caries process, especially when there is poor hygiene.

Williams Syndrome and 15q Duplication: Coincidence versus Association.

PubMed

Khokhar, Aditi; Agarwal, Swashti; Perez-Colon, Sheila

2017-01-01

Williams syndrome is a multisystem disorder caused by contiguous gene deletion in 7q11.23, commonly associated with distinctive facial features, supravalvular aortic stenosis, short stature, idiopathic hypercalcemia, developmental delay, joint laxity, and a friendly personality. The clinical features of 15q11q13 duplication syndrome include autism, mental retardation, ataxia, seizures, developmental delay, and behavioral problems. We report a rare case of a girl with genetically confirmed Williams syndrome and coexisting 15q duplication syndrome. The patient underwent treatment for central precocious puberty and later presented with primary amenorrhea. The karyotype revealed 47,XX,+mar. FISH analysis for the marker chromosome showed partial trisomy/tetrasomy for proximal chromosome 15q (15p13q13). FISH using an ELN -specific probe demonstrated a deletion in the Williams syndrome critical region in 7q11.23. To our knowledge, a coexistence of Williams syndrome and 15q duplication syndrome has not been reported in the literature. Our patient had early pubertal development, which has been described in some patients with Williams syndrome. However, years later after discontinuing gonadotropin-releasing hormone analogue treatment, she developed primary amenorrhea.

Diagnosis and treatment of polycystic ovarian syndrome in adolescents.

PubMed

Nicandri, Katrina F; Hoeger, Kathleen

2012-12-01

To review what is understood about the pathophysiology of polycystic ovarian syndrome (PCOS), the diagnostic challenges of PCOS in adolescent women, associated risk factors, as well as the best evidence-based treatment options for adolescence. Diagnosing PCOS in adolescents requires a unique set of criteria for which no single marker currently exists. Adolescents at high risk for developing the syndrome are congenital virilization, low birth weight, premature pubarche, central precocious puberty, large for gestational age girls born to overweight mothers, obesity syndromes, insulin-resistant features, and girls born to parents with PCOS, central obesity, or diabetes in whom PCOS ought to be suspected when associated with irregular menses. Insulin, hyperandrogenemia, and adipocytokines are integral players in the pathophysiology of PCOS. PCOS may be an inheritable trait; however, no gene has yet been identified. Quality of life remains a concern for young women with PCOS. Lifestyle modifications geared to prevent long-term sequelae remain the first-line treatment in conjunction with oral contraceptive pills. Identifying PCOS in adolescents remains a diagnostic dilemma, but early intervention and treatment can improve long-term health.

Amenorrhoea and reversible infertility due to obstructive hydrocephalus: literature review and case report.

PubMed

Hamilton, Kimberly; Iskandar, Bermans

2018-02-12

Endocrine abnormalities are well-recognized consequences of intracranial pathology such as pituitary tumours. Less commonly, hydrocephalus may lead to dysfunction of the endocrine system, presenting as amenorrhoea or precocious puberty. We present a case report and literature review of hydrocephalus causing endocrine abnormalities including reversible infertility. A 34 year-old female presented with amenorrhoea and infertility. MRI showed a third ventricular mass and hydrocephalus. The amenorrhoea resolved within weeks of endoscopic third ventriculostomy and tumour biopsy; pregnancy ensued within 6 months. Thirty-two cases of hydrocephalus-related amenorrhoea were reported between 1915 and 2007. All patients who underwent modern hydrocephalus treatment experienced partial or complete resolution of endocrine dysfunction. Successful pregnancy was reported in three patients, as in our case presentation. While mechanisms of dysfunction have not been completely elucidated, studies point toward loss of GnRH pulsatility due to compression of the medio-basal hypothalamic structures. Hydrocephalus can cause endocrine dysfunction, including amenorrhoea, which may reverse with CSF diversion. Therefore, cranial imaging is an important component in the evaluation of such endocrine abnormalities.

Fertility Preservation in Klinefelter Syndrome Patients during the Transition Period.

PubMed

Rives, Nathalie; Rives, Aurélie; Rondanino, Christine; Castanet, Mireille; Cuny, Ariane; Sibert, Louis

2018-01-01

Spermatozoa have occasionally been identified in ejaculate of adult Klinefelter syndrome (KS) patients but very exceptionally in KS adolescents. Spermatozoa can also be retrieved in testicular tissue of KS adolescents. The testis may also harbor spermatogonia and noncompletely differentiated germ cells. Neither clinical features nor hormonal parameters could predict germ cell recovery in KS adults or adolescents. No predictive factors can actually demonstrate that early diagnosis of KS would allow increasing the chance of sperm retrieval even if it has been suggested that semen quality may decline with age in KS patients. Leydig cell dysfunction may also be another factor that might affect the spermatogenesis process in XXY adolescents. Fertility preservation might be preferentially proposed in KS adolescents when semen sampling is possible, when the patient is able to consider alternative options to become a father, and to accept germ cell retrieval failure. However, precocious diagnosis of KS has also to be considered because it might not solely improve the possibility of fertility preservation after the onset of puberty, but also the medical care and the quality of life of these patients. © 2018 S. Karger AG, Basel.

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia.

PubMed

Deshpande, Saurabh S; Shetty, Devdas; Saifi, Shenaz

2017-01-01

Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of.

Sonographic Appearance of Testicular Adrenal Rest Tumour in a Patient with Congenital Adrenal Hyperplasia

PubMed Central

Shetty, Devdas; Saifi, Shenaz

2017-01-01

Summary Background Testicular adrenal rest tumours (TARTs) are benign testicular masses that are found in inadequately treated patients with congenital adrenal hyperplasia (CAH). Recognizing this association and identifying characteristic ultrasound features of TARTs is important so as to avoid misdiagnosing them as malignancies, which can lead to unnecessary interventions. Case Report We describe a case of a 9-year-old boy, with a diagnosis of CAH and precocious puberty, who was referred to our department for an ultrasound evaluation of the abdomen and scrotum. On ultrasound, there were well-defined, heterogeneous, predominantly hypoechoic, round-to-oval masses in both testes. Taking into account the presence of CAH and a typical sonographic appearance of bilateral testicular masses, a diagnosis of testicular adrenal rest tumour was made; biopsy was deferred and hormonal treatment was modified. Conclusions Prompt diagnosis of testicular adrenal rest tumours is essential, as it only indicates inadequate hormonal control. Moreover, it can prevent unnecessary biopsies and orchidectomies, and can maintain fertility. TARTs have a typical imaging appearance that every radiologist must be aware of. PMID:29662583

McCune Albright syndrome in association with excessive GH secretion: case report.

PubMed

Özsu, Elif; Mutlu, Gül Yeşiltepe; Çizmecioğlu, Filiz Mine; Hatun, Şükrü

2015-06-01

McCune-Albright Syndrome is a rare syndrome characterized with excessive function of peripheral endocrine organs and activating mutations of the stimulatory G protein alpha subunit are involved in the pathogenesis. The three main findings of the disease include hyperpigmented café au lait spots, fibrous dysplasia and increased endocrine functions and excessive secretion of growth hormone is observed in 21% of the patients. Clinical signs may be missed in these patients because of precocious puberty and craniofacial fibrous dysplasia. Since radiotherapy causes to sarcomatous changes and transsphenoidal surgery may cause to severe thickening in the cranial bones, they are not appropriate treatment options and medical treatment is recommended. Bromocriptine, cabergoline and octreotide or different combinations of these drugs are used in treatment and pegvisomant has also been used in recent years. Here, we present a male patient aged 12 years and 7 months to show gigantism as a rare clinical reflection of McCune-Albright Syndrome with an excessive height (197 cm), café au lait spots, growht hormone levels which could not be supressed with oral glucose tolerance test and increased prolactin levels.

Food Restriction Increases Acquisition, Persistence and Drug Prime-Induced Expression of a Cocaine-Conditioned Place Preference in Rats

PubMed Central

Zheng, Danielle; de Vaca, Soledad Cabeza; Carr, Kenneth D.

2011-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. PMID:22074687

Food restriction increases acquisition, persistence and drug prime-induced expression of a cocaine-conditioned place preference in rats.

PubMed

Zheng, Danielle; Cabeza de Vaca, Soledad; Carr, Kenneth D

2012-01-01

Cocaine conditioned place preference (CPP) is more persistent in food-restricted than ad libitum fed rats. This study assessed whether food restriction acts during conditioning and/or expression to increase persistence. In Experiment 1, rats were food-restricted during conditioning with a 7.0 mg/kg (i.p.) dose of cocaine. After the first CPP test, half of the rats were switched to ad libitum feeding for three weeks, half remained on food restriction, and this was followed by CPP testing. Rats tested under the ad libitum feeding condition displayed extinction by the fifth test. Their CPP did not reinstate in response to overnight food deprivation or a cocaine prime. Rats maintained on food restriction displayed a persistent CPP. In Experiment 2, rats were ad libitum fed during conditioning with the 7.0 mg/kg dose. In the first test only a trend toward CPP was displayed. Rats maintained under the ad libitum feeding condition did not display a CPP during subsequent testing and did not respond to a cocaine prime. Rats tested under food-restriction also did not display a CPP, but expressed a CPP following a cocaine prime. In Experiment 3, rats were ad libitum fed during conditioning with a 12.0 mg/kg dose. After the first test, half of the rats were switched to food restriction for three weeks. Rats that were maintained under the ad libitum condition displayed extinction by the fourth test. Their CPP was not reinstated by a cocaine prime. Rats tested under food-restriction displayed a persistent CPP. These results indicate that food restriction lowers the threshold dose for cocaine CPP and interacts with a previously acquired CPP to increase its persistence. In so far as CPP models Pavlovian conditioning that contributes to addiction, these results suggest the importance of diet and the physiology of energy balance as modulatory factors. Copyright © 2011 Elsevier Inc. All rights reserved.

Cell-penetrating peptide-doxorubicin conjugate loaded NGR-modified nanobubbles for ultrasound triggered drug delivery.

PubMed

Lin, Wen; Xie, Xiangyang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yang

2016-01-01

A new drug-targeting system for CD13(+) tumors has been developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, the CPP-doxorubicin conjugate (CPP-DOX) was entrapped in the asparagine-glycine-arginine (NGR) peptide modified NB (CPP-DOX/NGR-NB) and the penetration of CPP-DOX was temporally masked; local ultrasound stimulation could trigger the CPP-DOX release from NB and activate its penetration. The CPP-DOX/NGR-NBs had particle sizes of about 200 nm and drug entrapment efficiency larger than 90%. In vitro release results showed that over 85% of the encapsulated DOX or CPP-DOX would release from NBs in the presence of ultrasound, while less than 1.5% of that (30 min) without ultrasound. Cell experiments showed the higher cellular CPP-DOX uptake of CPP-DOX/NGR-NB among the various NB formulations in Human fibrosarcoma cells (HT-1080, CD13(+)). The CPP-DOX/NGR-NB with ultrasound treatment exhibited an increased cytotoxic activity than the one without ultrasound. In nude mice xenograft of HT-1080 cells, CPP-DOX/NGR-NB with ultrasound showed a higher tumor inhibition effect (3.1% of T/C%, day 24), longer median survival time (50 days) and excellent body safety compared with the normal DOX injection group. These results indicate that the constructed vesicle would be a promising drug delivery system for specific cancer treatment.

The impact of a highly visible display of cerebral perfusion pressure on outcome in individuals with cerebral aneurysms.

PubMed

Kirkness, Catherine J; Burr, Robert L; Cain, Kevin C; Newell, David W; Mitchell, Pamela H

2008-01-01

Nurses' ability to rapidly detect decreases in cerebral perfusion pressure (CPP), which may contribute to secondary brain injury, may be limited by poor visibility of CPP displays. To evaluate the impact of a highly visible CPP display on the functional outcome in individuals with cerebral aneurysms. Patients with cerebral aneurysms (n = 100) who underwent continuous CPP monitoring were enrolled and randomized to beds with or without the additional CPP display. Six-month outcome was assessed. Functional outcome was not significantly different between control and intervention groups after controlling for initial neurologic condition (odds ratio .904, 95% confidence interval 0.317 to 2.573). However, greater time below CPP thresholds (55 to 70 mm Hg) was significantly associated with poorer outcome (P = .005 to .010). Although the enhanced CPP display was not associated with significantly better outcome, longer periods of CPP below set levels were associated with poorer outcome.

Biochemical transformation of calciprotein particles in uraemia.

PubMed

Smith, Edward R; Hewitson, Tim D; Hanssen, Eric; Holt, Stephen G

2018-05-01

Calciprotein particles (CPP) have emerged as nanoscale mediators of phosphate-induced toxicity in Chronic Kidney Disease (CKD). Uraemia favors ripening of the particle mineral content from the amorphous (CPP-I) to the crystalline state (CPP-II) but the pathophysiological significance of this transformation is uncertain. Clinical studies suggest an association between CPP ripening and inflammation, vascular dysfunction and mortality. Although ripening has been modelled in vitro, it is unknown whether particles synthesised in serum resemble their in vivo counterparts. Here we show that in vitro formation and ripening of CPP in uraemic serum is characterised by extensive physiochemical rearrangements involving the accretion of mineral, loss of surface charge and transformation of the mineral phase from a spherical arrangement of diffuse domains of amorphous calcium phosphate to densely-packed lamellar aggregates of crystalline hydroxyapatite. These physiochemical changes were paralleled by enrichment with small soluble apolipoproteins, complement factors and the binding of fatty acids. In comparison, endogenous CPP represent a highly heterogeneous mixture of particles with characteristics mostly intermediate to synthetic CPP-I and CPP-II, but are also uniquely enriched for carbonate-substituted apatite, DNA fragments, small RNA and microbe-derived components. Pathway analysis of protein enrichment predicted the activation of cell death and pro-inflammatory processes by endogenous CPP and synthetic CPP-II alike. This comprehensive characterisation validates the use of CPP-II generated in uraemic serum as in vitro equivalents of their endogenous counterparts and provides insight into the nature and pathological significance of CPP in CKD, which may act as vehicles for various bioactive ligands. Copyright © 2018 Elsevier Inc. All rights reserved.

Intracranial pressure and cerebral perfusion pressure in patients developing brain death.

PubMed

Salih, Farid; Holtkamp, Martin; Brandt, Stephan A; Hoffmann, Olaf; Masuhr, Florian; Schreiber, Stephan; Weissinger, Florian; Vajkoczy, Peter; Wolf, Stefan

2016-08-01

We investigated whether a critical rise of intracranial pressure (ICP) leading to a loss of cerebral perfusion pressure (CPP) could serve as a surrogate marker of brain death (BD). We retrospectively analyzed ICP and CPP of patients in whom BD was diagnosed (n = 32, 16-79 years). Intracranial pressure and CPP were recorded using parenchymal (n = 27) and ventricular probes (n = 5). Data were analyzed from admission until BD was diagnosed. Intracranial pressure was severely elevated (mean ± SD, 95.5 ± 9.8 mm Hg) in all patients when BD was diagnosed. In 28 patients, CPP was negative at the time of diagnosis (-8.2 ± 6.5 mm Hg). In 4 patients (12.5%), CPP was reduced but not negative. In these patients, minimal CPP was 4 to 18 mm Hg. In 1 patient, loss of CPP occurred 4 hours before apnea completed the BD syndrome. Brain death was universally preceded by a severe reduction of CPP, supporting loss of cerebral perfusion as a critical step in BD development. Our data show that a negative CPP is neither sufficient nor a prerequisite to diagnose BD. In BD cases with positive CPP, we speculate that arterial blood pressure dropped below a critical closing pressure, thereby causing cessation of cerebral blood flow. Copyright © 2016 Elsevier Inc. All rights reserved.

Efficacy of CPP-ACP and CPP-ACPF on enamel remineralization - an in vitro study using scanning electron microscope and DIAGNOdent.

PubMed

Jayarajan, Jayanth; Janardhanam, P; Jayakumar, P

2011-01-01

Remineralization as a treatment procedure has received a lot of attention both from clinicians as well researchers. The objective of this in vitro study was to find out the efficacy of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium phosphate fluoride (CPP-ACPF) in remineralizing enamel surface on which artificial caries lesion had been created. The changes were analyzed using DIAGNOdent (KaVo) and scanning electron microscope (SEM). Ninety maxillary premolars were selected and divided into three groups of 30 teeth each: A (artificial saliva), B (CPP-ACP), and C (CPP-ACPF). All the samples were assessed using DIAGNOdent at the baseline and after demineralization and remineralization. Three samples were randomly selected from each group after remineralization for surface evaluation using SEM. Statistical analysis showed that group B {CPP-ACP (4.1 ± 1.8)} and group C {CPP-ACPF (4.8 ± 1.2)} had a significantly higher amount of remineralization than group A (1.7 ± 0.7). All the three groups showed a statistically significant amount of remineralization. However, because of the added benefit of fluoride (NaF 0.2%), CPP-ACPF (Tooth Mousse-Plus) showed marginally more amount of remineralization than CPP-ACP (Tooth Mousse).

Cycling peak power in obese and lean 6- to 8-year-old girls and boys.

PubMed

Aucouturier, Julien; Lazaar, Nordine; Doré, Eric; Meyer, Martine; Ratel, Sebastien; Duché, Pascale

2007-06-01

The purpose of this study was to investigate the possible effect of the difference in percentage body fat (%BF) and fat-free mass (FFM) on cycling peak power (CPP) in 6- to 8-year-old obese and lean untrained girls and boys. Obese (35 girls, 35 boys) and lean (35 girls, 35 boys) children were measured for obesity, %BF, calculated from skinfold measurements. FFM was calculated as body mass (BM) minus body fat. A force-velocity test on a cycle ergometer was used to measure CPP. CPP was related to anthropometric variables using standard and allometric models. CPP in absolute terms was higher in obese children than in lean children irrespective of gender. BM-related CPP was significantly lower in obese children than in lean ones, whereas no effect of obesity appeared on FFM-related CPP. Velocity at CPP (Vopt) was significantly lower and force at CPP (Fopt) was significantly higher in girls than in boys. Muscle power production was unaffected by obesity in children. Low BM-related CPP could explain the difficulty of taking up physical activities that are body-mass related in obese children. Gender difference for Vopt and Fopt shows that girls and boys may have different maturation patterns affecting CPP.

Sexual functioning in women with chronic pelvic pain: the role of anxiety and depression.

PubMed

ter Kuile, Moniek M; Weijenborg, Philomeen T M; Spinhoven, Philip

2010-05-01

Chronic pelvic pain (CPP) in women is a long lasting and often disabling condition. It seems reasonable to expect that as a result of the pain, extreme fatigue and/or emotional problems, women with CPP may report a variety of sexual problems. The present study investigated differences in the report of sexual problems in women with CPP compared with healthy controls, and whether the association of CPP with sexual problems was moderated or mediated by somatic and psychological factors as manifested in women suffering from CPP. One hundred fifty-four women with CPP and 58 age-matched controls completed self-report measures for sexual functioning, pain, physical impairment, anxiety, depression, and sexual and physical abuse. Golombok Rust Inventory of Sexual Satisfaction. Women with CPP reported higher levels of vaginistic complaints, sexual avoidance, nonsensuality and sexual dissatisfaction than healthy controls. Sexual problems were associated with anxiety, depression, and sexual abuse history but not with somatic factors as pain and physical impairment. Anxiety as well as depression, irrespective of the report of sexual abuse experiences, mediated the effect of CPP on sexual problems. Sexual abuse was a general predictor of sexual problems in both women with CPP and controls. Anxiety and depression constitute important factors in the evaluation of sexual problems in women with CPP.

[How can we determine the best cerebral perfusion pressure in pediatric traumatic brain injury?].

PubMed

Vuillaume, C; Mrozek, S; Fourcade, O; Geeraerts, T

2013-12-01

The management of cerebral perfusion pressure (CPP) is the one of the main preoccupation for the care of paediatric traumatic brain injury (TBI). The physiology of cerebral autoregulation, CO2 vasoreactivity, cerebral metabolism changes with age as well as the brain compliance. Low CPP leads to high morbidity and mortality in pediatric TBI. The recent guidelines for the management of CPP for the paediatric TBI indicate a CPP threshold 40-50 mmHg (infants for the lower and adolescent for the upper). But we must consider the importance of age-related differences in the arterial pressure and CPP. The best CPP is the one that allows to avoid cerebral ischaemia and oedema. In this way, the adaptation of optimal CPP must be individual. To assess this objective, interesting tools are available. Transcranial Doppler can be used to determine the best level of CPP. Other indicators can predict the impairment of autoregulation like pressure reactivity index (PRx) taking into consideration the respective changes in ICP and CPP. Measurement of brain tissue oxygen partial pressure is an other tool that can be used to determine the optimal CPP. Copyright © 2013 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. All rights reserved.

Incorporation of carrot pomace powder in wheat flour: effect on flour, dough and cookie characteristics.

PubMed

Ahmad, Mukhtar; Wani, Touseef Ahmed; Wani, S M; Masoodi, F A; Gani, Adil

2016-10-01

Carrot pomace powder (CPP) of 72 and 120 mesh sizes was incorporated in wheat flour at 10, 15 and 20 % level and its impact on flour, dough and cookie characteristics was evaluated. Protein content of the flour blends (8.84-7.88 %) decreased and fibre content (4.63-6.68 %) increased upon blending of CPP in wheat flour. Wheat flour containing 120 mesh CPP showed better functional properties [water absorption (1.16-1.47 %), oil absorption (1.11-1.39 %), solubility index (41-50 %) and swelling power (1.34-1.39)] than those containing 72 mesh. Water solvent retention capacity and sucrose solvent retention capacity increased while lactic acid solvent retention capacity and sodium carbonate solvent retention capacity decreased with blending of CPP. Water absorption, dough development time and degree of softening increased whereas, dough stability and mixing tolerance decreased with increasing CPP. The highest decrease in pasting was observed flour containing 72 mesh CPP. Rheology of dough containing 120 mesh CPP closely resembled the control. Color of flour and cookies increased with blending of CPP irrespective of mesh size. Antioxidant activity of cookies was higher than the flour blends. The cookies containing CPP of 72 mesh showed the lowest hardness. However, cookies containing CPP of 120 mesh showed the best sensory properties. Incorporation of 120 mesh CPP produced low gluten cookies with manageable flour and dough characteristics and better antioxidant and sensory properties.

Reinforced spatial alternation as an animal model of obsessive-compulsive disorder (OCD): investigation of 5-HT2C and 5-HT1D receptor involvement in OCD pathophysiology.

PubMed

Tsaltas, Eleftheria; Kontis, Dimitris; Chrysikakou, Sofia; Giannou, Haralambos; Biba, Angeliki; Pallidi, Stella; Christodoulou, Angeliki; Maillis, Antonis; Rabavilas, Andreas

2005-05-15

This study introduces a laboratory model of compulsive behavior based on persistence in the context of rewarded spatial alternation. Rats were screened for spontaneous persistence during T-maze reinforced alternation. Experiment 1: One high and one low spontaneous persistence group (n = 8) received 20 injections of fluoxetine, a matched pair saline, both followed by 4 days of meta-chlorophenylpiperazine (mCPP) challenge. Experiment 2: Five matched groups of rats (n = 9) received pretreatment (20 injections) with fluoxetine, mCPP, desipramine, diazepam or saline, followed by 4 days of mCPP challenge (fluoxetine in mCPP group). After washout, animals received 2 days of naratriptan, followed by another 2-day mCPP challenge. In both experiments mCPP significantly increased persistence in saline controls. Fluoxetine also acutely increased persistence scores: after a gradual return to baseline, these scores showed tolerance to mCPP. Experiment 1: This pattern was significant in high but not low initial persistence groups. Experiment 2: Fluoxetine and mCPP showed cross-tolerance. Neither desipramine nor diazepam protected against mCPP challenge. Persistence scores returned to baseline during washout and naratriptan and were thereafter increased by another mCPP challenge in all but the fluoxetine and mCPP groups, suggesting 5-HT2C receptor mediation. This model is based on spontaneous persistence behavior showing pharmacological responses concordant with those of compulsive symptomatology.

Conditioned Place Preference Induced by Licit Drugs: Establishment, Extinction, and Reinstatement

PubMed Central

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-01-01

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine. PMID:19082419

Conditioned place preference induced by licit drugs: establishment, extinction, and reinstatement.

PubMed

Liu, Yu; Le Foll, Bernard; Liu, Yanli; Wang, Xi; Lu, Lin

2008-12-14

The conditioned place preference (CPP) model has been widely used to evaluate the rewarding effects of abused drugs, and recently, the extinction and reinstatement phases of this paradigm have been used to assess relapse to drug seeking. The vast majority of studies have focused on CPP induced by illicit drugs, such as psychostimulants and opioids. Although legal psychoactive drugs, such as ethanol, nicotine, and caffeine, are more widely used than illegal drugs, the establishment, extinction, and reinstatement of CPP produced by these licit drugs are less well understood. The present review discusses the extant research on CPP induced by legal drugs. We first describe the CPP model and discuss the behavioral procedures used to induce CPP for ethanol, nicotine, and caffeine. We then summarize the neuronal substrates that underlie CPP induced by these drugs from a genetic perspective. Finally, we draw on findings from pharmacological studies and discuss the neurotransmitters and neurohormones underlying CPP produced by ethanol, nicotine, and caffeine.

THE ENDOCANNABINOID SYSTEM MODULATES THE VALENCE OF THE EMOTION ASSOCIATED TO FOOD INGESTION

PubMed Central

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, O.

2010-01-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant, or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide and if such CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. PMID:21182571

η6-Cycloparaphenylene transition metal complexes: synthesis, structure, photophysical properties, and application to the selective monofunctionalization of cycloparaphenylenes.

PubMed

Kubota, Natsumi; Segawa, Yasutomo; Itami, Kenichiro

2015-01-28

The synthesis, structure, photophysical properties, and reactivity of cycloparaphenylenes (CPPs) coordinated to group 6 transition metal fragments are described. The η(6)-coordination of [9]CPP or [12]CPP with M(CO)6 (M = Cr, Mo, W) afforded the corresponding [n]CPP-M(CO)3 complexes (n = 9, 12; M = Cr, Mo, W). In the (1)H NMR spectra of these complexes, characteristic upfield-shifted singlet signals corresponding to the four hydrogen atoms attached to the coordinated C6H4 ring of the CPPs were observed at 5.4-5.9 ppm. The complex [9]CPP-Cr(CO)3 could be successfully isolated in spite of its instability. X-ray crystallographic analysis and computational studies of [9]CPP-Cr(CO)3 revealed that chromium-CPP coordination occurs at the convex surface of [9]CPP both in the solid state and in solution. TD-DFT calculations suggested that the emerging high-wavenumber absorption peak upon coordination of [9]CPP to Cr(CO)3 should be assigned to a weak HOMO-LUMO transition. Moreover, by using the complex [9]CPP-Cr(CO)3, a rapid and highly monoselective CPP functionalization has been achieved. The established one-pot method, consisting of complexation, deprotonation, nucleophilic substitution, and decomplexation steps, yielded silyl-, boryl-, and methoxycarbonyl-substituted CPPs in up to 93% yield relative to reacted starting material.

Cell-penetrating peptide-siRNA conjugate loaded YSA-modified nanobubbles for ultrasound triggered siRNA delivery.

PubMed

Xie, Xiangyang; Yang, Yanfang; Lin, Wen; Liu, Hui; Liu, Hong; Yang, Yang; Chen, Ying; Fu, Xudong; Deng, Jianping

2015-12-01

Due to the absence of effective in vivo delivery systems, the employment of small interference RNA (siRNA) in the clinic has been hindered. In this paper, a new siRNA targeting system for EphA2-positive tumors was developed, based on ultrasound-sensitive nanobubbles (NBs) and cell-permeable peptides (CPPs). Here, a CPP-siRNA conjugate (CPP-siRNA) was entrapped in an ephrin mimetic peptide (YSA peptide)-modified NB (CPP-siRNA/YSA-NB) and the penetration of the CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research demonstrated that the CPP-siRNA/YSA-NBs had particle sizes of approximately 200 nm and a siRNA entrapment efficiency of more than 85%. The in vitro release results showed that over 90% of the encapsulated CPP-siRNA released from the NBs in the presence of ultrasound, while less than 1.5% of that (30 min) released without ultrasound. Cell experiments showed a the higher CPP-siRNA cellular uptake of CPP-siRNA/YSA-NB among the various formulations in human breast adenocarcinoma cells (MCF-7, EphA2 positive cells). Additionally, after systemic administration in mice, CPP-siRNA/YSA-NB accumulated in the tumor, augmented c-Myc silencing and delayed tumor progression. In conclusion, the application of CPP-siRNA/YSA-NB with ultrasound may provide a strategy for the selective and efficient delivery of siRNA. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic psychosocial stress causes delayed extinction and exacerbates reinstatement of ethanol-induced conditioned place preference in mice.

PubMed

Bahi, Amine; Dreyer, Jean-Luc

2014-01-01

We have shown previously, using an animal model of voluntary ethanol intake and ethanol-conditioned place preference (EtOH-CPP), that exposure to chronic psychosocial stress induces increased ethanol intake and EtOH-CPP acquisition in mice. Here, we examined the impact of chronic subordinate colony (CSC) exposure on EtOH-CPP extinction, as well as ethanol-induced reinstatement of CPP. Mice were conditioned with saline or 1.5 g/kg ethanol and were tested in the EtOH-CPP model. In the first experiment, the mice were subjected to 19 days of chronic stress, and EtOH-CPP extinction was assessed during seven daily trials without ethanol injection. In the second experiment and after the EtOH-CPP test, the mice were subjected to 7 days of extinction trials before the 19 days of chronic stress. Drug-induced EtOH-CPP reinstatement was induced by a priming injection of 0.5 g/kg ethanol. Compared to the single-housed colony mice, CSC mice exhibited increased anxiety-like behavior in the elevated plus maze (EPM) and the open field tests. Interestingly, the CSC mice showed delayed EtOH-CPP extinction. More importantly, CSC mice showed increased alcohol-induced reinstatement of the EtOH-CPP behavior. Taken together, this study indicates that chronic psychosocial stress can have long-term effects on EtOH-CPP extinction as well as drug-induced reinstatement behavior and may provide a suitable model to study the latent effects of chronic psychosocial stress on extinction and relapse to drug abuse.

A 10-yr Analysis of Chronic Pelvic Pain and Chronic Opioid Therapy in the Women Veteran Population.

PubMed

Cichowski, Sara B; Rogers, Rebecca G; Komesu, Yuko; Murata, Erin; Qualls, Clifford; Murata, Allison; Murata, Glen

2018-05-18

Chronic pelvic pain (CPP) affects an estimated 30% of women Veterans. Previous research shows high rates of narcotic abuse in the women Veteran population. Narcotics are not recommended for the treatment of CPP. Understanding how CPP impacts narcotic prescribing in the women Veteran population is critical to addressing the public health crisis of opioid abuse. Our objective was to compare chronic opioid therapy (COT) prescribed 5 yr prior to and following CPP diagnosis and to identify predictors of COT as well as adverse events associated with COT. We choose to look at 10 yr of data because we thought this time period would provide unique insight into the longitudinal associations of CPP and COT and was available in the database. Women with non-cancer CPP were included for analyses from the Veteran's Affairs Corporate Database Warehouse. COT was defined as 90 d of opiates/calendar year for each of the 5 yr proceeding and following the diagnosis of CPP. Patient characteristics and potential variables influencing COT were collected. We compared baseline demographics between the women who received COT to the women who did not receive COT to find additional demographic predictors of COT in association with CPP. Multivariable analysis identified predictors of COT in this population of women with CPP. We utilized an interrupted time series analysis to understand the impact of the diagnosis of CPP on COT. A total of 49,601 women met inclusion criteria with an average age of 40.1 ± 11.5 yr; 37.3% self-characterized as being a racial minority and 24% had a history of military sexual trauma. Chronic use increased significantly (p < 0.001) in the 5 yr preceding the diagnosis of CPP from 6.3% (n = 3124) of women at time -5 to 13.6% (n = 6746) at time 0. In the first year following the diagnosis of CPP, 16.8% (n = 8,333) of women with CPP met the criteria for COT (p < 0.001) and 15% (n = 7440) of women with CPP remained in the COT group for the remaining 5 yr following the diagnosis. On average women in the COT group had 250-292 d of opioids/year. When comparing women who received chronic narcotics following the diagnosis of CPP versus those who did not receive chronic narcotics, women who received COT were older, more likely to smoke and more frequently diagnosed with other pain conditions such as back pain, headaches, and fibromyalgia. (All p < 0.001). In the multivariable model, predictors of COT following CPP diagnosis included prior COT (OR = 10.0 (95% CI 9.4, 10.6), a positive history of military sexual trauma, smoking, and other chronic pain conditions. The distinct pattern of prescribing shown in this cohort may mean COT is prescribed for CPP and this prescribing pattern contributes to the adverse events associated with COT. As COT is not recommended for CPP, physicians need more education on the therapies available to help CPP patients.

[Remineralization of enamel promoted by casein phosphopeptide-amorphous calcium phosphate with different concentration of fluorin].

PubMed

Liu, Lu; Yang, Lin; Zou, Min

2013-10-01

To evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) combined with different concentrations of fluoride on demineralization of enamel remineralization. Extracted premolar teeth for orthodontic reason were immersed into lactic acid gel to prepare artificial white spot lesions. Then the specimens were randomly assigned to 3 groups: 5% CPP-ACP group as control, 5% CPP-ACP +500 mg/L F- group and 5% CPP-ACP +900 mg/L F- group, which were measured by micro-hardness tester. SPSS 18.0 software package was used for data analysis. There were significant differences in micro-hardness between control group and experimental group 1 and experimental group 2 by SNK-q test (P<0.05). CPP-ACP can make the demineralization of enamel remineralization occurs. F can promote the CPP-ACP remineralization. The increase of fluoride can make the CPP-ACP remineralization better below 1000-1500 mg/L.

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP601) BASEMENT SHOWING PROCESS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

FLOOR PLAN OF MAIN PROCESSING BUILDING (CPP-601) BASEMENT SHOWING PROCESS CORRIDOR AND EIGHTEEN CELLS. TO LEFT IS LABORATORY BUILDING (CPP-602). INL DRAWING NUMBER 200-0601-00-706-051981. ALTERNATE ID NUMBER CPP-E-1981. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CALCIPROTEIN PARTICLE FORMATION IN PERITONEAL DIALYSIS EFFLUENT IS DEPENDENT ON DIALYSATE CALCIUM CONCENTRATION.

PubMed

Cai, Michael M; Smith, Edward R; Kent, Annette; Huang, Louis; Hewitson, Tim D; McMahon, Lawrence P; Holt, Stephen G

2018-05-23

The accumulation of fetuin-A-containing calciprotein particles (CPP) in the serum of patients with renal disease and those with chronic inflammation may be involved in driving sterile inflammation and extraosseous mineral deposition. We previously showed that both fetuin-A and CPP were present in the peritoneal dialysis (PD) effluent of stable PD patients. It is unknown whether different PD fluids might affect the formation of CPP in vivo Method: Peritoneal effluent from 12 patients was collected after a 6-hour dwell with 7 different commercial PD fluids. Calciprotein particles and inflammatory cytokines were measured by flow cytometry. High inter-subject variability in CPP concentration was observed. Peritoneal dialysis fluids containing 1.75 mmol/L calcium were associated with enhanced formation of CPP in vivo , compared with fluids containing 1.25 mmol/L calcium. Osmotic agent, fluid pH, and glucose concentration did not affect CPP formation. Peritoneal dialysis effluent CPP levels were not associated with changes in inflammatory cytokines. High calcium-containing PD fluids favor intraperitoneal CPP formation. This finding may have relevance for future PD fluid design.

Retention in plaque and remineralization of enamel lesions by various forms of calcium in a mouthrinse or sugar-free chewing gum.

PubMed

Reynolds, E C; Cai, F; Shen, P; Walker, G D

2003-03-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes incorporated into sugar-free chewing gum have been shown to remineralize enamel subsurface lesions in situ. The aim of this study was to compare the ability of CPP-ACP, with that of other forms of calcium, to be retained in supragingival plaque and remineralize enamel subsurface lesions in situ when delivered in a mouthrinse or sugar-free gum in randomized, double-blind trials. In the mouthrinse study, only the CPP-ACP-containing mouthrinse significantly increased plaque calcium and inorganic phosphate levels, and the CPP were immunolocalized to the surfaces of bacterial cells as well as the intercellular matrix. In the chewing gum studies, the gum containing the CPP-ACP, although not containing the most calcium per piece of gum, produced the highest level of enamel remineralization independent of gum-chewing frequency and duration. The CPP could be detected in plaque extracts 3 hrs after subjects chewed the CPP-ACP-containing gum. The results showed that CPP-ACP were superior to other forms of calcium in remineralizing enamel subsurface lesions.

The endocannabinoid system modulates the valence of the emotion associated to food ingestion.

PubMed

Méndez-Díaz, Mónica; Rueda-Orozco, Pavel Ernesto; Ruiz-Contreras, Alejandra Evelyn; Prospéro-García, Oscar

2012-07-01

Endocannabinoids (eCBs) are mediators of the homeostatic and hedonic systems that modulate food ingestion. Hence, eCBs, by regulating the hedonic system, may be modulating the valence of the emotion associated to food ingestion (positive: pleasant or negative: unpleasant). Our first goal was to demonstrate that palatable food induces conditioned place preference (CPP), hence a positive-valence emotion. Additionally, we analyzed if this CPP is blocked by AM251, inducing a negative valence emotion, meaning avoiding the otherwise pursued compartment. The second goal was to demonstrate that CPP induced by regular food would be strengthened by the simultaneous administration of anandamide or oleamide, and if such, CPP is blocked by AM251. Finally, we tested the capacity of eCBs (without food) to induce CPP. Our results indicate that rats readily developed CPP to palatable food, which was blocked by AM251. The CPP induced by regular food was strengthened by eCBs and blocked by AM251. Finally, oleamide, unlike anandamide, induced CPP. These results showed that eCBs mediate the positive valence (CPP) of the emotion associated to food ingestion. It was also observed that the blockade of the CB1 receptor causes a loss of correlation between food and CPP (negative valence: avoidance). These data further support the role of eCBs as regulators of the hedonic value of food. © 2010 The Authors. Addiction Biology © 2010 Society for the Study of Addiction.

Extinction of opiate reward reduces dendritic arborization and c-Fos expression in the nucleus accumbens core.

PubMed

Leite-Morris, Kimberly A; Kobrin, Kendra L; Guy, Marsha D; Young, Angela J; Heinrichs, Stephen C; Kaplan, Gary B

2014-04-15

Recurrent opiate use combined with environmental cues, in which the drug was administered, provokes cue-induced drug craving and conditioned drug reward. Drug abuse craving is frequently linked with stimuli from a prior drug-taking environment via classical conditioning and associative learning. We modeled the conditioned morphine reward process by using acquisition and extinction of conditioned place preference (CPP) in C57BL/6 mice. Mice were trained to associate a morphine injection with a drug context using a classical conditioning paradigm. In morphine conditioning (0, 0.25, 0.5, 1, 5, or 10 mg/kg) experimental mice acquired a morphine CPP dose response with 10mg/kg as most effective. During morphine CPP extinction experiments, mice were divided into three test groups: morphine CPP followed by extinction training, morphine CPP followed by sham extinction, and saline controls. Extinction of morphine CPP developed within one extinction experiment (4 days) that lasted over two more trials (another 8 days). However, the morphine CPP/sham extinction group retained a place preference that endured through all three extinction trials. Brains were harvested following CPP extinction and processed using Golgi-Cox impregnation. Changes in dendritic morphology and spine quantity were examined in the nucleus accumbens (NAc) Core and Shell neurons. In the NAcCore only, morphine CPP/extinguished mice produced less dendritic arborization, and a decrease in neuronal activity marker c-Fos compared to the morphine CPP/sham extinction group. Extinction of morphine CPP is associated with decreased structural complexity of dendrites in the NAcCore and may represent a substrate for learning induced structural plasticity relevant to addiction. Published by Elsevier B.V.

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats

PubMed Central

Salti, Ahmad; Kummer, Kai K.; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2016-01-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. PMID:26300300

Social interaction reward decreases p38 activation in the nucleus accumbens shell of rats.

PubMed

Salti, Ahmad; Kummer, Kai K; Sadangi, Chinmaya; Dechant, Georg; Saria, Alois; El Rawas, Rana

2015-12-01

We have previously shown that animals acquired robust conditioned place preference (CPP) to either social interaction alone or cocaine alone. Recently it has been reported that drugs of abuse abnormally activated p38, a member of mitogen-activated protein kinase family, in the nucleus accumbens. In this study, we aimed to investigate the expression of the activated form of p38 (pp38) in the nucleus accumbens shell and core of rats expressing either cocaine CPP or social interaction CPP 1 h, 2 h and 24 h after the CPP test. We hypothesized that cocaine CPP will increase pp38 in the nucleus accumbens shell/core as compared to social interaction CPP. Surprisingly, we found that 24 h after social interaction CPP, pp38 neuronal levels were decreased in the nucleus accumbens shell to the level of naïve rats. Control saline rats that received saline in both compartments of the CPP apparatus and cocaine CPP rats showed similar enhanced p38 activation as compared to naïve and social interaction CPP rats. We also found that the percentage of neurons expressing dopaminergic receptor D2R and pp38 was also decreased in the shell of the nucleus accumbens of social interaction CPP rats as compared to controls. Given the emerging role of p38 in stress/anxiety behaviors, these results suggest that (1) social interaction reward has anti-stress effects; (2) cocaine conditioning per se does not affect p38 activation and that (3) marginal stress is sufficient to induce p38 activation in the shell of the nucleus accumbens. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

PubMed

Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

2012-01-01

The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

Casein phosphopeptide-amorphous calcium phosphate and shear bond strength of adhesives to primary teeth enamel.

PubMed

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-02-01

CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel.

Facilitated extinction of morphine conditioned place preference with Tat-GluA2(3Y) interference peptide.

PubMed

Dias, C; Wang, Y T; Phillips, A G

2012-08-01

Neuroplasticity including long-term depression (LTD) has been implicated in both learning processes and addiction. LTD can be blocked by intravenous administration of the interference peptide Tat-GluA2(3Y) that prevents regulated endocytosis of the alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) receptor. In this study, Tat-GluA2(3Y) was used to assess the role of LTD in the induction, expression, extinction and reinstatement of morphine-induced conditioned place preference (CPP). CPP was established in rats by pairing morphine (5 mg/kg, i.p.) or saline with a specific environmental context using a balanced protocol. Tat-GluA2(3Y) (0; 1.5; 2.25 nmol/g; i.v.), scrambled peptide (Tat-GluA2(Sc)), or vehicle was administered during the acquisition phase or prior to the test for CPP. Tat-GluA2(3Y) had no effect on the induction or initial expression of morphine-induced CPP. Rats that received Tat-GluA2(3Y) or Tat-GluA2(Sc) during acquisition were subsequently tested for 11 consecutive days in order to extinguish morphine CPP. CPP was then reinstated by an injection of morphine (5 mg/kg, i.p.). Co-administration of morphine and Tat-GluA2(3Y) during acquisition greatly facilitated extinction of CPP without affecting morphine-induced reinstatement of CPP. Using an intermittent retest schedule with bi-weekly tests to measure the maintenance of CPP, Tat-GluA2(3Y) during the acquisition phase had no effect on the maintenance of CPP. We propose that co-administration of Tat-GluA2(3Y) with morphine during acquisition of CPP weakens the association between morphine and contextual cues leading to rapid extinction of morphine CPP with repeated daily testing. Copyright © 2012 Elsevier B.V. All rights reserved.

Morphine-induced conditioned place preference in rhesus monkeys: Resistance to inactivation of insula and extinction.

PubMed

Wu, XuJun; Zhao, Ning; Bai, Fan; Li, ChuanYu; Liu, CiRong; Wei, JingKuan; Zong, Wei; Yang, LiXin; Ryabinin, Andrey E; Ma, YuanYe; Wang, JianHong

2016-05-01

Drug addicts experience strong craving episodes in response to drug-associated cues. Attenuating these responses using pharmacological or behavioral approaches could aid recovery from addiction. Cue-induced drug seeking can be modeled using the conditioned place preference procedure (CPP). Our previous work showed that conditioned place preference (CPP) can be induced by administration of increasing doses of morphine in rhesus monkeys. Here, we investigated whether expression of morphine-induced CPP can be attenuated by inhibiting activity of insular cortex or by repeated unreinforced exposures to the CPP test. The insula has been demonstrated to be involved in addiction to several drugs of abuse. To test its role in morphine CPP, bilateral cannulae were implanted into the insula in seven adult monkeys. The CPP was established using a biased apparatus by intramuscular injections of morphine at increasing doses (1.5, 3.0 and 4.5mg/kg) for each monkey. After the monkeys established morphine CPP, their insulae were reversibly inactivated by bilateral microinjection with 5% lidocaine (40μl) prior to the post-conditioning test (expression) of CPP using a within-subject design. The microinjections of lidocaine failed to affect CPP expression when compared to saline injections. We subsequently investigated morphine-associated memory during six episodes of CPP tests performed in these monkeys over the following 75.0±0.2months. While the preference score showed a declining trend with repeated testing, morphine-induced CPP was maintained even on the last test performed at 75months post-conditioning. This observation indicated strong resistance of morphine-induced memories to extinction in rhesus monkeys. Although these data do not confirm involvement of insula in morphine-induced CPP, our observation that drug-associated memories can be maintained over six drug-free years following initial experience with morphine has important implications for treatment of drug addiction using extinction therapy. Copyright © 2016 Elsevier Inc. All rights reserved.

Taming the Wildness of "Trojan-Horse" Peptides by Charge-Guided Masking and Protease-Triggered Demasking for the Controlled Delivery of Antitumor Agents.

PubMed

Shi, Nian-Qiu; Qi, Xian-Rong

2017-03-29

Cell-penetrating peptide (CPP), also called "Trojan Horse" peptide, has become a successful approach to deliver various payloads into cells for achieving the intracellular access. However, the "Trojan Horse" peptide is too wild, not just to "Troy", but rather widely distributed in the body. Thus, there is an urgent need to tame the wildness of "Trojan Horse" peptide for targeted delivery of antineoplastic agents to the tumor site. To achieve this goal, we exploit a masked CPP-doxorubicin conjugate platform for targeted delivery of chemotherapeutic drugs using charge-guided masking and protease-triggered demasking strategies. In this platform, the cell-penetrating function of the positively CPP (d-form nonaarginine) is abrogated by a negatively shielding peptide (masked CPP), and between them is a cleavable substrate peptide by the protease (MMP-2/9). Protease-triggered demasking would occur when the masked CPP reached the MMP-2/9-riched tumor. The CPP-doxorubicin conjugate (CPP-Dox) and the masked CPP-Dox conjugate (mCPP-Dox) were used as models for the evaluation of masking and demasking processes. It was found that exogenous MMP-2/9 could effectively trigger the reversion of CPP-cargo in this conjugate, and this trigger adhered to the Michaelis-Menten kinetics profile. This conjugate was sensitive to the trigger of endogenous MMP-2/9 and could induce enhanced cytotoxicity toward MMP-2/9-rich tumor cells. In vivo antitumor efficacy revealed that this masked conjugate had considerable antitumor activity and could inhibit the tumor growth at a higher level relative to CPP-cargo. Low toxicity in vivo showed the noticeably decreased wildness of this conjugate toward normal tissues and more controllable entry of antitumor agents into "Troy". On the basis of analyses in vitro and in vivo, this mCPP-cargo conjugate delivery system held an improved selectivity toward MMP-2/9-rich tumors and would be a promising strategy for tumor-targeted treatment.

Sexual selection leads to a tenfold difference in reproductive success of alternative reproductive tactics in male Atlantic salmon

NASA Astrophysics Data System (ADS)

Tentelier, Cédric; Lepais, Olivier; Larranaga, Nicolas; Manicki, Aurélie; Lange, Frédéric; Rives, Jacques

2016-06-01

The precocious maturation of some male Atlantic salmon ( Salmo salar L.) has become a textbook example of alternative mating tactics, but the only estimates of reproductive success available so far are either the collective contribution of precocious males to reproduction in the wild or individual reproductive success in oversimplified experimental conditions. Using genetic parentage analysis on anadromous and precocious potential spawners and their offspring, we quantified components of individual reproductive success of both tactics in a natural population. On average, precocious males produced 2.24 (variance 67.62) offspring, against 27.17 (3080) for anadromous males. For both tactics, most of the variance in reproductive success was due to mating success, with 83 % of precocious males having no mate, against 50 % for anadromous males. Body size increased reproductive success of anadromous males and tended to decrease precocious males' reproductive success. Although these results do not solve the coexistence of alternative reproductive tactics (ARTs) in Atlantic salmon, their inclusion in comprehensive models of lifetime reproductive success should shed light on the evolution of precocious maturation in Atlantic salmon and its effect on the selection of phenotypic traits.

Sexual selection leads to a tenfold difference in reproductive success of alternative reproductive tactics in male Atlantic salmon.

PubMed

Tentelier, Cédric; Lepais, Olivier; Larranaga, Nicolas; Manicki, Aurélie; Lange, Frédéric; Rives, Jacques

2016-06-01

The precocious maturation of some male Atlantic salmon (Salmo salar L.) has become a textbook example of alternative mating tactics, but the only estimates of reproductive success available so far are either the collective contribution of precocious males to reproduction in the wild or individual reproductive success in oversimplified experimental conditions. Using genetic parentage analysis on anadromous and precocious potential spawners and their offspring, we quantified components of individual reproductive success of both tactics in a natural population. On average, precocious males produced 2.24 (variance 67.62) offspring, against 27.17 (3080) for anadromous males. For both tactics, most of the variance in reproductive success was due to mating success, with 83% of precocious males having no mate, against 50% for anadromous males. Body size increased reproductive success of anadromous males and tended to decrease precocious males' reproductive success. Although these results do not solve the coexistence of alternative reproductive tactics (ARTs) in Atlantic salmon, their inclusion in comprehensive models of lifetime reproductive success should shed light on the evolution of precocious maturation in Atlantic salmon and its effect on the selection of phenotypic traits.

Efficient siRNA Delivery Using Novel Cell-Penetrating Peptide-siRNA Conjugate-Loaded Nanobubbles and Ultrasound.

PubMed

Xie, Xiangyang; Lin, Wen; Li, Mingyuan; Yang, Yang; Deng, Jianping; Liu, Hui; Chen, Ying; Fu, Xudong; Liu, Hong; Yang, Yanfang

2016-06-01

Because of the absence of tolerable and effective carriers for in vivo delivery, the applications of small interfering RNA (siRNA) in the clinic for therapeutic purposes have been limited. In this study, development of a novel siRNA delivery system based on ultrasound-sensitive nanobubbles (NBs, nano-sized echogenic liposomes) and cell-permeable peptides (CPPs) is described. A CPP-siRNA conjugate was entrapped in an NB, (CPP-siRNA)-NB, and the penetration of CPP-siRNA was temporally masked; local ultrasound stimulation triggered the release of CPP-siRNA from the NBs and activated its penetration. Subsequent research revealed that the (CPP-siRNA)-NBs had a mean particle size of 201 ± 2.05 nm and a siRNA entrapment efficiency >85%. In vitro release results indicated that >90% of the encapsulated CPP-siRNA was released from NBs in the presence of ultrasound, whereas <1.5% (30 min) was released in the absence of ultrasound. Cell experiments indicated higher cellular CPP-siRNA uptake of (CPP-siRNA)-NBs with ultrasound among the various formulations in human breast adenocarcinoma cells (HT-1080). Additionally, after systemic administration in mice, (CPP-siRNA)-NBs accumulated in the tumor, augmented c-myc silencing and delayed tumor progression. In conclusion, the application of (CPP-siRNA)-NBs with ultrasound may constitute an approach to selective targeted delivery of siRNA. Copyright © 2016 World Federation for Ultrasound in Medicine & Biology. Published by Elsevier Inc. All rights reserved.

A cluster of culture positive gonococcal infections but with false negative cppB gene based PCR.

PubMed

Lum, G; Freeman, K; Nguyen, N L; Limnios, E A; Tabrizi, S N; Carter, I; Chambers, I W; Whiley, D M; Sloots, T P; Garland, S M; Tapsall, J W

2005-10-01

To describe the prevalence and characteristics of isolates of Neisseria gonorrhoeae grown from urine samples that produced negative results with nucleic acid amplification assays (NAA) targeting the cppB gene. An initial cluster of culture positive, but cppB gene based NAA negative, gonococcal infections was recognised. Urine samples and suspensions of gonococci isolated over 9 months in the Northern Territory of Australia were examined using cppB gene based and other non-cppB gene based NAA. The gonococcal isolates were phenotyped by determining the auxotype/serovar (A/S) class and genotyped by pulsed field gel electrophoresis (PFGE). 14 (9.8%) of 143 gonococci isolated were of A/S class Pro(-/)Brpyut, indistinguishable on PFGE and negative in cppB gene based, but not other, NAA. This cluster represents a temporal and geographic expansion of a gonococcal subtype lacking the cppB gene with consequent loss of sensitivity of NAA dependent on amplification of this target. Gonococci lacking the cppB gene have in the past been more commonly associated with the PAU-/PCU- auxotype, a gonococcal subtype hitherto infrequently encountered in Australia. NAA based on the cppB gene as a target may produce false positive as well as false negative NAA. This suggests that unless there is continuing comparison with culture to show their utility, cppB gene based NAA should be regarded as suboptimal for use either as a diagnostic or supplemental assay for diagnosis of gonorrhoea, and NAA with alternative amplification targets should be substituted.

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms

PubMed Central

Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E. A.; Huq, N. Laila; Reynolds, Eric C.

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge. PMID:27589264

Casein Phosphopeptide-Amorphous Calcium Phosphate Reduces Streptococcus mutans Biofilm Development on Glass Ionomer Cement and Disrupts Established Biofilms.

PubMed

Dashper, Stuart G; Catmull, Deanne V; Liu, Sze-Wei; Myroforidis, Helen; Zalizniak, Ilya; Palamara, Joseph E A; Huq, N Laila; Reynolds, Eric C

2016-01-01

Glass ionomer cements (GIC) are dental restorative materials that are suitable for modification to help prevent dental plaque (biofilm) formation. The aim of this study was to determine the effects of incorporating casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) into a GIC on the colonisation and establishment of Streptococcus mutans biofilms and the effects of aqueous CPP-ACP on established S mutans biofilms. S. mutans biofilms were either established in flow cells before a single ten min exposure to 1% w/v CPP-ACP treatment or cultured in static wells or flow cells with either GIC or GIC containing 3% w/w CPP-ACP as the substratum. The biofilms were then visualised using confocal laser scanning microscopy after BacLight LIVE/DEAD staining. A significant decrease in biovolume and average thickness of S. mutans biofilms was observed in both static and flow cell assays when 3% CPP-ACP was incorporated into the GIC substratum. A single ten min treatment with aqueous 1% CPP-ACP resulted in a 58% decrease in biofilm biomass and thickness of established S. mutans biofilms grown in a flow cell. The treatment also significantly altered the structure of these biofilms compared with controls. The incorporation of 3% CPP-ACP into GIC significantly reduced S. mutans biofilm development indicating another potential anticariogenic mechanism of this material. Additionally aqueous CPP-ACP disrupted established S. mutans biofilms. The use of CPP-ACP containing GIC combined with regular CPP-ACP treatment may lower S. mutans challenge.

NeuroD modulates opioid agonist-selective regulation of adult neurogenesis and contextual memory extinction.

PubMed

Zheng, Hui; Zhang, Yue; Li, Wen; Loh, Horace H; Law, Ping-Yee

2013-04-01

Addictive drugs, including opioids, modulate adult neurogenesis. In order to delineate the probable implications of neurogenesis on contextual memory associated with addiction, we investigated opioid agonist-selective regulation of neurogenic differentiation 1 (NeuroD) activities under the conditioned place preference (CPP) paradigm. Training mice with equivalent doses of morphine and fentanyl produced different CPP extinction rates without measurable differences in the CPP acquisition rate or magnitude. Fentanyl-induced CPP required much longer time for extinction than morphine-induced CPP. We observed a parallel decrease in NeuroD activities and neurogenesis after morphine-induced CPP, but not after fentanyl-induced CPP. Increasing NeuroD activities with NeuroD-lentivirus (nd-vir) injection at the dentate gyrus before CPP training reversed morphine-induced decreases in NeuroD activities and neurogenesis, and prolonged the time required for extinction of morphine-induced CPP. On the other hand, decreasing NeuroD activities via injection of miRNA-190-virus (190-vir) reversed the fentanyl effect on NeuroD and neurogenesis and shortened the time required for extinction of fentanyl-induced CPP. Another contextual memory task, the Morris Water Maze (MWM), was affected similarly by alteration of NeuroD activities. The reduction in NeuroD activities either by morphine treatment or 190-vir injection decreased MWM task retention, while the increase in NeuroD activities by nd-vir prolonged MWM task retention. Thus, by controlling NeuroD activities, opioid agonists differentially regulate adult neurogenesis and subsequent contextual memory retention. Such drug-related memory regulation could have implications in eventual context-associated relapse.

The effect of casein phosphopeptide-amorphous calcium phosphate and a cola soft drink on in vitro enamel hardness.

PubMed

Panich, Muratha; Poolthong, Suchit

2009-04-01

The authors conducted an in vitro study to compare the hardness of normal enamel with enamel eroded by a cola soft drink and enamel remineralized by casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) or artificial saliva. The authors immersed 40 extracted sound central and lateral incisors alternately in a cola soft drink or artificial saliva for 10 cycles of five seconds each. They repeated this procedure two times at six-hour intervals. They divided the samples randomly into four groups and applied CPP-ACP to the samples, immersed them in artificial saliva, deionized water or both. They measured the hardness on the labial surface at baseline, after erosion and after remineralization and analyzed the data with one-way repeated-measures analysis of variance and two-way analysis of variance. The cola soft drink significantly decreased enamel hardness. CPP-ACP and CPP-ACP and artificial saliva significantly increased the hardness of eroded enamel. CPP-ACP and CPP-ACP and artificial saliva increased the hardness of eroded enamel significantly more than artificial saliva did. CPP-ACP increased the hardness of eroded enamel. CPP-ACP had a greater effect on enamel hardness than did artificial saliva. Consumption of a cola soft drink can cause tooth erosion. CPP-ACP may significantly remineralize eroded enamel compared with artificial saliva.

[Effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching].

PubMed

Lu, Jing; Ding, Xiao-jun; Yu, Xiao-ping; Gong, Yi-ming

2015-10-01

To evaluate the effect of casein phosphopeptide-amorphouscalcium phosphate (CPP-ACP) treatment on the shear bond strength of orthodontic brackets after tooth bleaching. One hundred extracted human premolars were randomly divided and treated according to 5 groups (n=20) : (1) no treatment; (2) 10% carbamide peroxide bleaching; (3) 38% hydrogen peroxide bleaching; (4)10% carbamide peroxide bleaching and CPP-ACP paste; (5)38% hydrogen peroxide bleaching and CPP-ACP paste. In all groups, the brackets were bonded using a conventional acid-etch and bond system (Transbond XT, 3M Unitek, Monrovia, Calif). The shear bond strength adhesive remnant index (ARI) of the brackets were determined and the data was analyzed by ANOVA and Bonferroni test using SPSS13.0 software package. The use of 10% carbamide peroxide and 38% hydrogen peroxide bleaching significantly decreased the shear bond strength of orthodontic brackets when compared with untreated group (P<0.05). After combination of tooth bleaching and CPP-ACP treatment, group 4 (10% carbamide peroxide bleaching + CPP-ACP) and group 5 (38% hydrogen peroxide bleaching + CPP-ACP) showed higher levels of shear bond strength than group 2 and 3; however, no significant difference was found (P>0.05). The ARI did not show any significant difference before and after CPP-ACP treatment. After tooth bleaching, CPP-ACP treatment have little influence on the shear bond strength of orthodontic brackets.

Cannabinoid 1 receptor blockade in the dorsal hippocampus prevents the reinstatement but not acquisition of morphine-induced conditioned place preference in rats.

PubMed

Zhao, Xin; Yao, Li; Wang, Fang; Zhang, Han; Wu, Li

2017-07-05

The cannabinoid 1 receptors (CB1Rs) signaling is strongly linked to conditioned rewarding effects of opiates. Learned associations between environmental contexts and discrete cues and drug use play an important role in the maintenance and/or relapse of morphine addiction. Although previous studies suggest that context-dependent morphine treatment alters endocannabinoid signaling and synaptic plasticity in the hippocampus, the role of endocannabinoid in morphine conditioned place preference (CPP) and reinstatement remains unknown. In the present study, we found daily escalating doses of morphine induce significant CPP in rats. After the extinction of CPP, a priming dose of morphine was sufficient to reinstate morphine CPP and was associated with the elevated CB1R levels compared with saline control groups, suggesting upregulation of CB1R pathway in the hippocampus contribute to the reinstatement of morphine CPP. By using a pharmacological inhibitor of CB1R administered into the dorsal hippocampus, we showed that blockade of CB1R signaling did not alter the morphine CPP acquisition but inhibited the reinstatement of morphine CPP. In addition, no effects were induced upon CB1R blockade in the prefrontal cortex on reinstatement of morphine CPP. These studies reveal region-specific effects of hippocampal blockade of CB1R signaling pathway on the reinstatement of morphine CPP.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction.

PubMed

El Rawas, Rana; Klement, Sabine; Kummer, Kai K; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex-nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction.

Storage study and quality evaluation of coconut protein powder.

PubMed

Naik, Aduja; Prakash, Maya; R, Ravi; Raghavarao, Ksms

2013-11-01

Coconut skim milk and insoluble protein are 2 major byproducts in the production of virgin coconut oil. Coconut skim milk was homogenized along with insoluble protein and spray dried to obtain a value-added product, namely, coconut protein powder (CPP). This study deals with the storage study of CPP under different conditions (refrigerated [control], ambient and accelerated). CPP samples were withdrawn periodically at designated intervals of 15 d for accelerated and control, and 30 d for ambient condition. CPP stored at different conditions exhibited marginal moisture uptake (by 0.74 % w/w for control, 0.76 % w/w for ambient, and 1.26 % w/w for accelerated condition) and as a result, had very little effect on the functional properties of the powder. Withdrawn CPP was tested for sensory quality aspects and subjected to instrumental analysis as well. Withdrawn CPP was incorporated as a milk substitute in dessert (Kheer). Quantitative descriptive analysis of the powder and product (Kheer) showed no significant difference in attributes of CPP during the storage period of 2 mo. Electronic nose analysis revealed that CPP samples were not much different with respect to aroma pattern matching, respectively. © 2013 CSIR-Central Food Technological Research Institute.

Design, synthesis, and functional testing of recombinant cell penetrating peptides

NASA Astrophysics Data System (ADS)

Widyaningtyas, S. T.; Soebandrio, A.; Ibrahim, F.; Bela, B.

2017-08-01

Cell penetrating peptides (CPP) are one of the most attractive DNA delivery systems currently in development. In this research, in silico CPP development was performed based on a literature study to look for peptides that induce endosome escape, have the ability to bind DNA, and pass through cell membranes and/or nuclear membranes with a final goal of creating a new CPP to be used as a DNA delivery system. We report herein the successful isolation of three candidate CPP molecules, which have all been successfully expressed and purified by NiNTA. One of the determinants of CPP success as a DNA carrier is the ability of the CPP to bind and protect DNA from the effects of nucleases. The DNA binding test results show that all three CPPs can bind to DNA and protect it from the effects of serum nucleases. These three CPP candidates designed in silico and synthesized in the prokaryote system are eligible candidates for further testing of their ability to deliver DNA in vitro and in vivo.

Incorporation of casein phosphopeptide-amorphous calcium phosphate into a glass-ionomer cement.

PubMed

Mazzaoui, S A; Burrow, M F; Tyas, M J; Dashper, S G; Eakins, D; Reynolds, E C

2003-11-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) nanocomplexes have been shown to prevent demineralization and promote remineralization of enamel subsurface lesions in animal and in situ caries models. The aim of this study was to determine the effect of incorporating CPP-ACP into a self-cured glass-ionomer cement (GIC). Incorporation of 1.56% w/w CPP-ACP into the GIC significantly increased microtensile bond strength (33%) and compressive strength (23%) and significantly enhanced the release of calcium, phosphate, and fluoride ions at neutral and acidic pH. MALDI mass spectrometry also showed casein phosphopeptides from the CPP-ACP nanocomplexes to be released. The release of CPP-ACP and fluoride from the CPP-ACP-containing GIC was associated with enhanced protection of the adjacent dentin during acid challenge in vitro.

Trazodone generates m-CPP: in 2008 risks from m-CPP might outweigh benefits of trazodone.

PubMed

Kast, Richard E

2009-01-01

Since deleterious effects of m-CPP, the primary catabolic metabolite of trazodone, were last reviewed 2 years ago, research data continue to accrue showing that clinically significant levels of m-CPP (a) are generated in patients using trazodone for sleep and (b) are present 24 h a day and (c) have potentially serious ill effects. This commentary argues that the documented potential for harm and multiple risks of m-CPP outweigh potential benefits of trazodone, given the development and marketing of many safer alternatives since trazodone's introduction in the 1980s.

Cognitive Processes that Underlie Mathematical Precociousness in Young Children

ERIC Educational Resources Information Center

Swanson, H. Lee

2006-01-01

The working memory (WM) processes that underlie young children's (ages 6-8 years) mathematical precociousness were examined. A battery of tests that assessed components of WM (phonological loop, visual-spatial sketchpad, and central executive), naming speed, random generation, and fluency was administered to mathematically precocious and…

NORTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. HOT PILOT PLANT BUILDING (CPP-640) APPEARS IN RIGHT OF PHOTO. THE REMOTE ANALYTICAL FACILITY (CPP-627) WAS LOCATED ON CONCRETE PAD IN FOREGROUND. INL PHOTO NUMBER HD-54-33-3. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Casein Phosphopeptide-Amorphous Calcium Phosphate and Shear Bond Strength of Adhesives to Primary Teeth Enamel

PubMed Central

Farokh Gisovar, Elham; Hedayati, Nassim; Shadman, Niloofar; Shafiee, Leila

2015-01-01

Background: CPP-ACP (Phosphopeptide-Amorphous Calcium Phosphate) has an important role in caries prevention in pediatric patients. This study was done, because of the great use of CPP-ACP and the need for restoration for teeth treated with CPP-ACP as well as the importance of shear bond strength of adhesives in the success of restorations. Objectives: This study aimed to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on shear bond strength of dental adhesives to enamel of primary teeth molars. Materials and Methods: This in vitro study was conducted on 180 extracted primary molars. They were randomly divided into 6 groups and each group was divided into 2 subgroups (treated with CPP-ACP and untreated). In subgroups with CPP-ACP, enamel was treated with CPP-ACP paste 1 h/d for 5 days. Types of adhesives that were evaluated in this study were Tetric N-Bond, AdheSE, AdheSE One F, single Bond 2, SE Bond, and Adper Prompt L-Pop. Shear bond strength was tested with a universal testing machine and mode of failure was evaluated under stereomicroscope. Data were analyzed by T test, 2-way analysis of variance (ANOVA), Tukey and Fisher exact test using SPSS18. P < 0.05 was considered as significance level. Results: Shear bond strengths of different adhesive systems to enamel of primary teeth treated and untreated with CPP-ACP showed no significant difference (P > 0.05). Mode of failure in all groups regardless of CPP-ACP administration was mainly adhesive type. Our results indicated that CPP-ACP did not affect shear bond strength of studied adhesives to primary teeth enamel. Conclusions: To have a successful and durable composite restoration, having a high strength bonding is essential. Considering the wide use of CPP-ACP in preventing tooth decay and the role of adhesive shear bond strength (SBS) in success of composite restoration, we conducted the present study to evaluate the effect of CPP-ACP on the SBS of adhesives to primary teeth enamel. PMID:25793113

Effects of the κ-opioid receptor on the inhibition of 100 Hz electroacupuncture on cocaine-induced conditioned place preference

PubMed Central

Hou, Bingjun

2016-01-01

The administration of 100 Hz electroacupuncture has been demonstrated to suppress cocaine-induced conditioned place preference (CPP) in rats, and there is evidence that the κ-opioid receptor may have a role in cocaine addiction. The present study sought to explore the mechanisms underlying the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP in rats. A rat model of cocaine-induced CPP was used in the present study to investigate the following: i) Naloxone treatment (5 and 10 mg/kg) following 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, revealing that a high dose (10 mg/kg) of naloxone blocked the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP; ii) nor-binaltorphimine (nor-BNI) on 100 Hz electroacupuncture-mediated inhibition on cocaine-induced CPP, which indicated that administration of 10 µg/5 µl and 0.3 µg/1 µl nor-BNI intracerebroventricularly and via the nucleus accumbens, respectively, reversed the inhibitory effects of 100 Hz electroacupuncture on cocaine-induced CPP, and that injection of nor-BNI in different brain areas of rats blocks the inhibitory effects of electroacupuncture on cocaine-induced CPP; and iv) 100 Hz electroacupuncture on the mRNA expression levels of the κ-opioid receptor in the rat nucleus accumbens and amygdala, which established that mRNA expression levels of κ-opioid receptor in the nucleus accumbens were increased with 100 Hz electroacupuncture plus cocaine-induced CPP. Overall, the results of the present study indicated that 100 Hz electroacupuncture was able to suppress cocaine-induced CPP via the κ-opioid receptor in the nucleus accumbens. PMID:27588082

Inhibitory effects of processed Aconiti tuber on morphine-induced conditioned place preference in rats.

PubMed

Wu, Guiyun; Huang, Wenqi; Zhang, Hui; Li, Qiaobo; Zhou, Jun; Shu, Haihua

2011-06-14

Our previous studies indicated that processed Aconiti tuber (PAT), a traditional Chinese herbal medicine, had antinociceptive effects and inhibitory effects on morphine tolerance by activation of kappa-opioid receptor (KOR). Preclinical studies also demonstrated that KOR agonists functionally attenuate addictive behaviors of morphine, such as conditioned place preference (CPP). Therefore, we hypothesize that PAT may inhibit morphine-induced CPP in rats. (1) Five groups of rats (n=8 for each group) were alternately subcutaneous (s.c.) injected with morphine 10mg/kg (one group receive normal saline as a control) and normal saline for 8 days and oral co-administrated with distilled water or PAT 0.3, 1.0, or 3.0 g/kg daily on days 2-9 during CPP training, respectively. (2) Other four groups of rats were randomly s.c. injected with nor-binaltorphimine (nor-BNI; 5mg/kg) or normal saline (as a control) 120 min before alternately s.c. with morphine and normal saline and oral co-administrated with distilled water or PAT 3.0 g/kg daily. Each rat was acquired pre-conditioning and post-conditioning CPP data and assayed dynorphin concentrations by radioimmunoassay in rat's nucleus accumbens (NAc) after CPP training. (1) PAT 1.0 or 3.0 g/kg dose-dependently decreased the morphine-induced increase of CPP scores. (2) Nor-BNI completely antagonized the inhibition of PAT on morphine-induced CPP. (3) PAT dose-dependently increased dynorphin content in rats' NAc after CPP training. (1) PAT dose-dependently inhibited morphine-induced CPP. (2) The inhibition of PAT on morphine-induced CPP was probably due to activation of KOR by increasing dynorphin release in rats' NAc. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Impact of endocrine hyperfunction and phosphate wasting on bone in McCune-Albright syndrome.

PubMed

Lala, R; Matarazzo, P; Andreo, M; Defilippi, C; de Sanctis, C

2002-01-01

Skin dysplasia, as café-au-lait spots, bone fibrous dysplasia and peripheral endocrinopathies are the main clinical features of McCune-Albright syndrome (MAS). This illness is due to activating mutations of the Gsalpha protein and is spread with a mosaic pattern in affected tissues that consist of intermixed areas of normal and mutated cells. Peripheral endocrine secretion, free of hypothalamic pituitary control, is the hallmark of the endocrine syndromes: precocious puberty, Cushing's syndrome, hyperthyroidism and gigantism/acromegaly. In addition, phosphate wasting as hyperphosphaturia is often present. The impact of hormonal hypersecretion and phosphate loss on the bones of patients with MAS is poorly understood both in normal and fibrous bone tissue. As hypercortisolism and hyperthyroidism increase bone resorption, hyperestrogenism and growth hormone hypersecretion stimulate bone growth and mineralization, and phosphate wasting reduces bone mineral content. All these actions can be exerted at varying times and degrees in a single patient on lesional and non-lesional bones. Sonographic evidence of multiple diffused hyperechogenic spots in the testes of patients with MAS do not seem to be related to alterations in calcium-phosphate metabolism but rather to zonal dysplasia/hyperplasia of testicular tissue.

Measuring estrogens in women, men, and children: Recent advances 2012-2017.

PubMed

Smy, Laura; Straseski, Joely

2018-05-22

The measurement of estrogens is important for diagnosing and monitoring the health of women, men, and children. For example, for postmenopausal women or women undergoing treatment for breast cancer with aromatase inhibitors, the measurement of extremely low concentrations of estrogens in serum, especially estradiol, is problematic but essential for proper medical care. Achieving superb analytical sensitivity and specificity has been and continues to be a challenge for the clinical laboratory, but is a challenge that is being taken seriously. Focusing on publications from 2012 to 2017, this review will provide an overview of recent research in the development of methods to accurately and precisely measure estrogens, including a variety of estrogen metabolites. Additionally, the latest in clinical research involving estrogen measurement in women, men, and children will be presented to provide an update on the association of estrogens with diseases or conditions such as breast cancer, precocious puberty, infertility, and pregnancy. This research update will provide context as to why estrogen measurement is important and why laboratories are working hard to support the recommendations made by the Endocrine Society regarding estrogen measurement. Copyright © 2018 Elsevier Inc. All rights reserved.

Control of molting in crustacea

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

Skinner, D.M.; Graham, D.E.; Holland, C.A.

1982-01-01

The single, overriding event that occurs during all proecdysial periods in crustaceans is the synthesis of a new exoskeleton that encompasses an enlarged animal when the old shell is cast off. Regeneration of missing appendages and larval or puberty metamorphoses also occur during proecdysis. Proecdysial periods have been divided into substages defined by the occurrence of specific events. Although a number of factors must be postulated to account for individual proecdysial events, only the molting hormone, 20-hydroxyecdysone, has been identified and isolated. Much evidence indicates that the X-organ sinus glands complex, a neurosecretory tissue located in the eyestalks, is themore » source of a molt inhibiting hormone (MIH) responsible for maintaining animals in anecdysis. An exuviation factor has been proposed to support the extrication of the animal from the old exoskeleton. There is evidence for a limb growth inhibitory factor (LGIF) that affects the rate of growth of regenerating limbs. We are proposing an anecdysial limb autotomy factor (LAF/sub an/) that propels into precocious molts anecdysial limb autotomy factor (LAF/sub pro/) that interrupts the proecdysial period of animals that lose one or more normal or partially regenerated pereopods before a critical time in proecdysis.« less

What is known about sexual health after pediatric acquired brain injury: A scoping review.

PubMed

Simpson, Grahame; Simons-Coghill, Martine; Bates, Annerley; Gan, Caron

2017-01-01

Positive sexual development is a core task in the transition from childhood/adolescence to adulthood. Little is known about the extent of research addressing this topic after acquired brain injury (ABI). To identify publications (1980 to 2016) addressing positive sexual health among children/adolescents with ABI. A scoping review. A search conducted using OVID and PubMed databases yielded 2021 citations with 28 publications meeting the inclusion criteria (six reviews, one expert account, 19 observational and two intervention studies). Teenagers with ABI reported poorer body image, feeling less sexually or physically attractive than sex and age matched non brain-damaged controls. The one study with findings on sexual orientation, reported 15% of adolescents with ABI identified as lesbian, gay or bisexual. Precocious puberty was a rare outcome from ABI, but the most common focus of the publications (14/28). Finally, two case studies (genital touching and classroom masturbation respectively) found that behavioral interventions were an effective means of extinguishing inappropriate sexual behaviour after childhood ABI. Sexual health is a neglected area of research in post-ABI care for children/adolescents. A better understanding of the needs and challenges will help rehabilitation professionals and parents provide more informed and effective supports.

Brain regions associated with the acquisition of conditioned place preference for cocaine vs. social interaction

PubMed Central

El Rawas, Rana; Klement, Sabine; Kummer, Kai K.; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

Positive social interaction could play an essential role in switching the preference of the substance dependent individual away from drug related activities. We have previously shown that conditioned place preference (CPP) for cocaine at the dose of 15 mg/kg and CPP for four 15-min episodes of social interaction were equally strong when rats were concurrently conditioned for place preference by pairing cocaine with one compartment and social interaction with the other. The aim of the present study was to investigate the differential activation of brain regions related to the reward circuitry after acquisition/expression of cocaine CPP or social interaction CPP. Our findings indicate that cocaine CPP and social interaction CPP activated almost the same brain regions. However, the granular insular cortex and the dorsal part of the agranular insular cortex were more activated after cocaine CPP, whereas the prelimbic cortex and the core subregion of the nucleus accumbens were more activated after social interaction CPP. These results suggest that the insular cortex appears to be potently activated after drug conditioning learning while activation of the prelimbic cortex—nucleus accumbens core projection seems to be preferentially involved in the conditioning to non-drug stimuli such as social interaction. PMID:23015784

18-methoxycoronaridine blocks acquisition but enhances reinstatement of a cocaine place preference

PubMed Central

McCallum, Sarah E.; Glick, Stanley D.

2009-01-01

The iboga alkaloid congener, 18-methoxycoronaridine (18-MC), decreases self-administration of multiple drugs of abuse. Here, in a biased procedure, we investigated whether 18-MC would have a similar effect on the acquisition, expression and reinstatement of a cocaine conditioned place preference (CPP) in male, Sprague-Dawley rats. While 18-MC attenuated acquisition of a cocaine CPP, it had no effect on CPP expression, and enhanced the reinstatement of cocaine CPP following extinction. Our results are consistent with those obtained using ibogaine, but reinforce the notion that acquisition, expression and reinstatement of a CPP likely involve separate mechanisms. PMID:19442876

Community Influence on Precocious Transitions to Adulthood: Racial Differences and Mental Health Consequences

ERIC Educational Resources Information Center

Wickrama, K. A. S.; Merten, Michael J.; Elder, Glen H., Jr.

2005-01-01

The "rush to adulthood" is defined by precocious events that place excessive demands on youth who are not adequately prepared for the responsibilities of adulthood. This study investigates the influence of community disadvantage, family, and race on adolescent precocious life events and depressive symptoms in the transition to adulthood. The…

Methylone and mCPP, two new drugs of abuse?

PubMed

Bossong, M G; Van Dijk, J P; Niesink, R J M

2005-12-01

Recently, two new ecstasy-like substances, methylone and mCPP, were found in street drugs in the Netherlands by the Drugs Information and Monitoring System (DIMS). Methylone (3,4-methylenedioxymethcathinone) is the main ingredient of a new liquid designer drug that appeared on the Dutch drug market, called 'Explosion'. mCPP (meta-chlorophenylpiperazine) is a substance often used as a probe for the serotonin function in psychiatric research, and has now been found in street drugs, both in tablets and powders. Methylone as well as mCPP act on monoaminergic systems, resembling MDMA (3,4-methylenedioxymethamphetamine), with mCPP mainly affecting the serotonin system. The subjective effects of both new substances exhibit subtle differences with those of MDMA. Only little is known about the harmfulness of both methylone and mCPP. However, because of similarities between these substances and MDMA, risks common to MDMA cannot be excluded.

Evaluation of the rewarding properties of nicotine and caffeine by implementation of a five-choice conditioned place preference task in zebrafish.

PubMed

Faillace, M P; Pisera-Fuster, A; Bernabeu, R

2018-06-08

The rewarding properties of drugs in zebrafish can be studied using the conditioned place preference (CPP) paradigm. Most devices that have been used for CPP consist of two-half tanks with or without a central chamber. Here we evaluated the rewarding effects of nicotine and caffeine using a tank with five arms distributed radially from a central chamber that we have denoted Fish Tank Radial Maze (FTRM). Zebrafish were trained to associate nicotine or caffeine with a coloured arm. In testing sessions to assess CPP induction, between two and five different arms were available to explore. We found that when offering the two arms, one of them associated to the drug mediating conditioning for 14 days, zebrafish showed nicotine-induced CPP but not caffeine-induced CPP. When zebrafish had the option to explore drug-paired arms together with new coloured arms as putative distractors, the nicotine-CPP strength was maintained for at least three days. The presence of novel environments induced caffeine-CPP, which was still positive after three days of testing sessions. Complementary behavioural data supported these findings. Nicotine-CPP was prevented by the histone deacetylase inhibitor phenylbutyrate administered during conditioning; however, there were no effects on caffeine-CPP. The specific acetylation of lysine 9 in histone 3 (H3-K9) was increased in nicotine-conditioned zebrafish brains. This study suggests that novel environmental cues facilitate drug-environment associations, and hence, the use of drugs of abuse. Copyright © 2018 Elsevier Inc. All rights reserved.

Pharmacological reduction of adult hippocampal neurogenesis modifies functional brain circuits in mice exposed to a cocaine conditioned place preference paradigm.

PubMed

Castilla-Ortega, Estela; Blanco, Eduardo; Serrano, Antonia; Ladrón de Guevara-Miranda, David; Pedraz, María; Estivill-Torrús, Guillermo; Pavón, Francisco Javier; Rodríguez de Fonseca, Fernando; Santín, Luis J

2016-05-01

We investigated the role of adult hippocampal neurogenesis in cocaine-induced conditioned place preference (CPP) behaviour and the functional brain circuitry involved. Adult hippocampal neurogenesis was pharmacologically reduced with temozolomide (TMZ), and mice were tested for cocaine-induced CPP to study c-Fos expression in the hippocampus and in extrahippocampal addiction-related areas. Correlational and multivariate analysis revealed that, under normal conditions, the hippocampus showed widespread functional connectivity with other brain areas and strongly contributed to the functional brain module associated with CPP expression. However, the neurogenesis-reduced mice showed normal CPP acquisition but engaged an alternate brain circuit where the functional connectivity of the dentate gyrus was notably reduced and other areas (the medial prefrontal cortex, accumbens and paraventricular hypothalamic nucleus) were recruited instead of the hippocampus. A second experiment unveiled that mice acquiring the cocaine-induced CPP under neurogenesis-reduced conditions were delayed in extinguishing their drug-seeking behaviour. But if the inhibited neurons were generated after CPP acquisition, extinction was not affected but an enhanced long-term CPP retention was found, suggesting that some roles of the adult-born neurons may differ depending on whether they are generated before or after drug-contextual associations are established. Importantly, cocaine-induced reinstatement of CPP behaviour was increased in the TMZ mice, regardless of the time of neurogenesis inhibition. The results show that adult hippocampal neurogenesis sculpts the addiction-related functional brain circuits, and reduction of the adult-born hippocampal neurons increases cocaine seeking in the CPP model. © 2015 Society for the Study of Addiction.

Effect of baclofen on morphine-induced conditioned place preference, extinction, and stress-induced reinstatement in chronically stressed mice.

PubMed

Meng, Shanshan; Quan, Wuxing; Qi, Xu; Su, Zhiqiang; Yang, Shanshan

2014-01-01

A stress-induced increase in excitability can result from a reduction in inhibitory neurotransmission. Modulation of gamma-aminobutyric acid (GABA)ergic transmission is an effective treatment for drug seeking and relapse. This study investigated whether baclofen, a GABA(B) receptor agonist, had an impact on morphine-induced conditioned place preference (CPP), extinction, and stress-induced relapse in chronically stressed mice. Chronic stress was induced by restraining mice for 2 h for seven consecutive days. We first investigated whether chronic stress influenced morphine-induced CPP, extinction, and stress-induced relapse in the stressed mice. Next, we investigated whether three different doses of baclofen influenced chronic stress as measured by the expression of morphine-induced CPP. We chose the most effective dose for subsequent extinction and reinstatement experiments. Reinstatement of morphine-induced CPP was induced by a 6-min forced swim stress. Locomotor activity was also measured for each test. Chronic stress facilitated the expression of morphine-induced CPP and prolonged extinction time. Forced swim stress primed the reinstatement of morphine-induced CPP in mice. Baclofen treatment affected the impact of chronic stress on different phases of morphine-induced CPP. Our results showed that baclofen antagonized the effects of chronic stress on morphine-induced CPP. These findings suggest the potential clinical utility of GABA(B) receptor-positive modulators as an anti-addiction agent in people suffering from chronic stress.

Cellular Internalization of Fibroblast Growth Factor-12 Exerts Radioprotective Effects on Intestinal Radiation Damage Independently of FGFR Signaling

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

Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp; Umeda, Sachiko; Yasuda, Takeshi

2014-02-01

Purpose: Several fibroblast growth factors (FGFs) were shown to inhibit radiation-induced tissue damage through FGF receptor (FGFR) signaling; however, this signaling was also found to be involved in the pathogenesis of several malignant tumors. In contrast, FGF12 cannot activate any FGFRs. Instead, FGF12 can be internalized readily into cells using 2 cell-penetrating peptide domains (CPP-M, CPP-C). Therefore, this study focused on clarifying the role of FGF12 internalization in protection against radiation-induced intestinal injury. Methods and Materials: Each FGF or peptide was administered intraperitoneally to BALB/c mice in the absence of heparin 24 hours before or after total body irradiation withmore » γ rays at 9 to 12 Gy. Several radioprotective effects were examined in the jejunum. Results: Administration of FGF12 after radiation exposure was as effective as pretreatment in significantly promoting intestinal regeneration, proliferation of crypt cells, and epithelial differentiation. Two domains, comprising amino acid residues 80 to 109 and 140 to 169 of FGF12B, were identified as being responsible for the radioprotective activity, so that deletion of both domains from FGF12B resulted in a reduction in activity. Interestingly, these regions included the CPP-M and CPP-C domains, respectively; however, CPP-C by itself did not show an antiapoptotic effect. In addition, FGF1, prototypic FGF, possesses a domain corresponding to CPP-M, whereas it lacks CPP-C, so the fusion of FGF1 with CPP-C (FGF1/CPP-C) enhanced cellular internalization and increased radioprotective activity. However, FGF1/CPP-C reduced in vitro mitogenic activity through FGFRs compared with FGF1, implying that FGFR signaling might not be essential for promoting the radioprotective effect of FGF1/CPP-C. In addition, internalized FGF12 suppressed the activation of p38α after irradiation, resulting in reduced radiation-induced apoptosis. Conclusions: These findings indicate that FGF12 can protect the intestine against radiation-induced injury through its internalization, independently of FGFRs, suggesting that cellular uptake of FGF12 is an alternative signaling pathway useful for cancer radiation therapy.« less

Complementary and Alternative Medicine in the Treatment of Chronic Pelvic Pain in Women: What Is the Evidence?

PubMed

Paiva, Sara; Carneiro, Márcia Mendonça

2013-01-01

Chronic pelvic pain (CPP) is defined as pain of at least 6 months' duration that occurs in the lower abdomen or below the umbilicus and has resulted in functional or psychological disability or required intervention and treatment. Therapeutic interventions center around the treatment of CPP as a diagnosis in and of itself, and treatment of specific disorders that may be related to CPP. A multidisciplinary approach for diagnosis and treatment seems to be most effective for symptomatic relief. This paper reviews the evidence for such interventions as psychological treatments including the use of complementary and alternative medicine techniques for CPP in women. Unfortunately, finding the best evidence in this setting is difficult as only very few randomized controlled trials are available. A combination of treatments is usually required over time for the treatment of refractory CPP. The multifactorial nature of CPP needs to be discussed with the patient and a good rapport as well as a partnership needs to be developed to plan a management program with regular followup. Promotion of a multidisciplinary approach which includes complementary and alternative medicine techniques in managing CPP in women seems to yield the best results.

[Effects of propranolol on acquisition and retrieval of morphine- induced conditioned place preference memories in ICR mice].

PubMed

Mao, Yu; Yang, Shang-Chuan; Liu, Chang; Ma, Yuan-Ye; Hu, Xin-Tian

2011-12-01

To interfere with the drug-cue memory processes of addicts such as reconsolidation by the administration of the β-adrenergic receptor (β-AR) of norepinephrine (NE) antagonist propranolol (PRO) has become a potential therapy in the future to decrease or inhibit relapse. However, the relationship between PRO and the acquisition or retrieval of morphine-cue memory is not clear. This study examined the effects of PRO on the acquisition and retrieval of memories in morphine-induced conditioned place preference (CPP) mice model. We found that during memory acquisition period, PRO had no effects on the expression and extinction of morphine-CPP, which suggests that the β-AR was irrelevant to the CPP memory acquisition. However, during memory retrieval period, although PRO did not affect the expression of CPP, but it delayed the occurrence of CPP extinction, which indicates that PRO has an inhibit effect on CPP memory extinction, and β-AR plays an important role in modulating the extinction of morphine-CPP. Our study further improved the relationship between drug addiction and β-AR, and proposed a new theory to help developing potential therapy to cure addiction and other neuropsychiatric disorders.

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL WALL SECTIONS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111682. ALTERNATE ID NUMBER 8952-CPP-640-A-5. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP640). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111684. ALTERNATE ID NUMBER 8952-CPP-640-A-7. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

PLAN VIEW OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLAN VIEW OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS. INL DRAWING NUMBER 200-0603-00-706-051285. ALTERNATE ID NUMBER CPP-D-1285. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Hybrid 2D photonic crystal-assisted Lu3Al5O12:Ce ceramic-plate phosphor and free-standing red film phosphor for white LEDs with high color-rendering index.

PubMed

Park, Hoo Keun; Oh, Ji Hye; Kang, Heejoon; Zhang, Jian; Do, Young Rag

2015-03-04

This paper reports the combined optical effects of a two-dimensional (2D) SiNx photonic crystal layer (PCL)-assisted Lu3Al5O12:Ce (LuAG:Ce) green ceramic-plate phosphor (CPP) and a free-standing (Sr,Ca)AlSiN3:Eu red film phosphor to enhance luminous efficacy, color rendering index (CRI), and special CRI (R9) of LuAG:Ce CPP-capped white light-emitting diodes (LEDs) for high-power white LEDs at 350 mA. By introducing the 2D SiNx PCL, the luminous efficacy was improved by a factor of 1.25 and 1.15 compared to that of the conventional flat CPP-capped LED and the thickness-increased CPP-capped LED (with a thickness of 0.15 mm), respectively, while maintaining low color-rendering properties. The combining of the free-standing red film phosphor in the flat CPP-capped, the 2D PCL-assisted CPP-capped, and the thickness-increased CPP-capped LEDs led to enhancement of the CRI and the special CRI (R9); it also led to a decrease of the correlated color temperature (CCT) due to broad wavelength coverage via the addition of red emission. High CRI (94), natural white CCT (4450 K), and acceptable luminous efficacy (71.1 lm/W) were attained from the 2D PCL-assisted LuAG:Ce CPP/free-standing red film phosphor-based LED using a red phosphor concentration of 7.5 wt %. It is expected that the combination of the 2D PCL and the free-standing red film phosphor will be a good candidate for achieving a high-power white CPP-capped LED with excellent CRI.

Context-dependent effects of rimonabant on ethanol-induced conditioned place preference in female mice.

PubMed

Silva, Aline A F; Barbosa-Souza, Evelyn; Confessor-Carvalho, Cassio; Silva, Raiany R R; De Brito, Ana Carolina L; Cata-Preta, Elisangela G; Silva Oliveira, Thaynara; Berro, Lais F; Oliveira-Lima, Alexandre J; Marinho, Eduardo A V

2017-10-01

The CB1 receptor antagonist rimonabant has been previously found to prevent behavioral effects of drugs of abuse in a context-dependent manner, suggesting an important role of endocannabinoid signaling in drug-induced environmental conditioning. The aim of the present study was to evaluate the effects of rimonabant on ethanol-induced conditioned place preference (CPP) in female mice. Animals were conditioned with saline or ethanol (1.8g/kg) during 8 sessions, and subsequently treated with either saline or rimonabant (1 or 10mg/kg) in the CPP environment previously associated with saline (unpaired) or ethanol (paired) for 6 consecutive days. Animals were then challenged with ethanol (1.8g/kg) in the ethanol-paired environment and ethanol-induced CPP was quantified on the following day. While treatment with 1mg/kg rimonabant in the saline-associated environment had no effects on the subsequent expression of ethanol-induced CPP, it blocked the expression of CPP to ethanol when paired to the ethanol-associated environment. When given in the ethanol-paired environment, 10mg/kg rimonabant induced aversion to the ethanol-associated environment. The same aversion effect was observed for 10mg/kg rimonabant when given in the saline-associated environment, thereby potentiating the expression of ethanol-induced CPP. Importantly, rimonabant did not induce CPP or conditioned place aversion on its own. Controlling for the estrous cycle phase showed no influences of hormonal cycle on the development and expression of ethanol-induced CPP. Our data suggest that rimonabant reduces the rewarding properties of ethanol by abolishing drug-environment conditioning in the CPP paradigm in a context-dependent manner. Copyright © 2017 Elsevier B.V. All rights reserved.

The physical properties and ion release of CPP-ACP-modified calcium silicate-based cements.

PubMed

Dawood, A E; Manton, D J; Parashos, P; Wong, Rhk; Palamara, Jea; Stanton, D P; Reynolds, E C

2015-12-01

This study investigated the physical properties and ion release of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP)-modified calcium silicate-based cements (CSCs) and compared the properties of a trial mineral trioxide aggregate (MTA) with two commercially available CSCs, Biodentine(™) and Angelus(®) MTA. The setting time, solubility, compressive strength and Vickers surface microhardness of the three CSCs incorporated with 0%, 0.5%, 1.0%, 2.0% and 3.0% (w/w) CPP-ACP were investigated. Release of calcium (Ca(2+) ), phosphate ions (Pi ) and pH of the test cements were measured after 24, 72, 168 and 336 h of storage. The addition of up to 1.0% CPP-ACP into Biodentine(™) and 0.5% into the other cements did not adversely affect their physical properties except for the setting time. The addition of 0.5% CPP-ACP increased Ca(2+) released from Biodentine(™) (after 168 and 336 h), Angelus(®) MTA (after 168 h) and the trial MTA (after 72 h). The addition of 1.0-3.0% CPP-ACP increased Ca(2+) and Pi released from all the cements. Biodentine(™) released more Ca(2+) particularly in the early stages and showed shorter setting time and higher mechanical properties than the other cements. The mechanical properties of Angelus(®) MTA and the trial MTA were similar. All the cements produced highly alkaline storage solutions. Up to 1.0% CPP-ACP in Biodentine(™) improves Ca(2+) and Pi release and 0.5% CPP-ACP in Angelus(®) MTA and the trial MTA improves Ca(2+) release without altering the mechanical properties and solubility. The addition of CPP-ACP into CSCs prolonged the setting time. © 2015 Australian Dental Association.

The effects of d-govadine on conditioned place preference with d-amphetamine or food reward.

PubMed

Nesbit, Maya O; Dias, Carine; Phillips, Anthony G

2017-03-15

Tetrahydroprotoberberines (THPB) have a high affinity for dopamine (DA) D1 and D2 receptors and may provide a novel treatment for drug addiction. We assessed the effects of the THPB d-govadine on the acquisition, expression, extinction and reinstatement of d-amphetamine-(1.5mg/kg, i.p.) induced conditioned place preference (CPP). Furthermore, the effects of d-govadine on conditioned association between contextual stimuli and a natural reward were examined using food-induced CPP. In separate experiments, rats received d-govadine (0, 0.5 or 1.0mg/kg, i.p.) before a) each d-amphetamine injection during conditioning, b) expression of amphetamine-induced CPP, c) each extinction session, d) amphetamine-induced reinstatement of CPP, or e) placement into a compartment containing food during conditioning. Although d-govadine had no effect on acquisition of amphetamine CPP, treatment with d-govadine during acquisition dose-dependently extinguished a preference for the amphetamine-associated context more quickly than vehicle treatment. Moreover, d-govadine treatment facilitated the extinction of amphetamine CPP when given repeatedly throughout the extinction phase. Although the expression of amphetamine CPP was not affected by d-govadine administered prior to the expression test, amphetamine-induced reinstatement of CPP following an extinction period was blocked by d-govadine (1.0mg/kg). The intermediate dose of d-govadine blocked the acquisition of food CPP, whereas the high dose facilitated extinction of this preference as compared to vehicle-treated animals. Therefore, d-govadine attenuates the maintenance of conditioned associations between contextual stimuli and amphetamine or food reward, as well as amphetamine-induced reinstatement of drug seeking behaviour. As such, d-govadine may be a candidate for further development as a pharmacological treatment of psychostimulant drug dependence. Copyright © 2017 Elsevier B.V. All rights reserved.

Toward an understanding of disequilibrium dihedral angles in mafic rocks

USGS Publications Warehouse

Holness, Marian B.; Humphreys, Madeleine C.S.; Sides, Rachel; Helz, Rosalind T.; Tegner, Christian

2012-01-01

The median dihedral angle at clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, Θcpp, is generally lower than equilibrium (109˚ {plus minus} 2˚). Observation of a wide range of mafic bodies demonstrates that previous work on systematic variations of Θcpp is incorrect in several important respects. Firstly, the spatial distribution of plagioclase compositional zoning demonstrates that the final geometry of three-grain junctions, and hence Θcpp, is formed during solidification (the igneous process): sub-solidus textural modification in most dolerites and gabbros, previously thought to be the dominant control on Θcpp, is insignificant. Θcpp is governed by mass transport constraints, the inhibiting effects of small pore size on crystallization, and variation in relative growth rates of pyroxene and plagioclase. During rapid cooling, pyroxene preferentially fills wider pores while the narrower pores remain melt-filled, resulting in an initial value of Θcpp of 78˚, rather than 60˚ which would be expected if all melt-filled pores were filled with pyroxene. Lower cooling rates create a higher initial Θcpp due to changes in relative growth rates of the two minerals at the nascent three-grain junction. Low Θcpp (associated with cuspate clinopyroxene grains at triple junctions) can also be diagnostic of infiltration of previously melt-free rocks by late-stage evolved liquids (the metasomatic process). Modification of Θcpp by sub-solidus textural equilibration (the metamorphic process) is only important for fine-grained mafic rocks such as chilled margins and intra-plutonic chill zones. In coarse-grained gabbros from shallow crustal intrusions the metamorphic process occurs only in the centres of oikocrysts, associated with rounding of chadacrysts.

Regulation of extinction of cocaine-induced place preference by midkine is related to a differential phosphorylation of peroxiredoxin 6 in dorsal striatum.

PubMed

Gramage, Esther; Pérez-García, Carmen; Vicente-Rodríguez, Marta; Bollen, Silke; Rojo, Loreto; Herradón, Gonzalo

2013-09-15

The neurotrophic factors Midkine (MK) and Pleiotrophin (PTN) have been suggested to modulate drugs of abuse-induced effects. To test this hypothesis, cocaine (10 and 15mg/kg)-induced conditioned place preference (CPP) was rendered in PTN knockout (PTN-/-), MK knockout (MK-/-) and wild type (WT+/+) mice, and then extinguished after repeated saline injections (distributed in 4 extinction sessions). Cocaine induced a similar CPP in all the three genotypes. We found a significantly increased percentage of MK-/- mice that did not extinguish cocaine CPP at the end of the extinction sessions. Particularly, 40% of MK-/- mice did not extinguish cocaine (15mg/kg)-induced CPP compared to WT+/+ and PTN-/- mice (∼0-6%). Interestingly, we found that a greater magnitude of extinction of CPP after the first extinction session (5 days after last administration of cocaine) correlates with increased tyrosine phosphorylation of the enzyme peroxiredoxin 6 in the dorsal striatum of MK-/- mice. On the other hand, a greater magnitude of CPP extinction correlates with increased tyrosine phosphorylation of aconitase 2 in the prefrontal cortex of WT+/+ mice. In contrast, a lower magnitude of CPP extinction correlates with increased phosphorylation of aconitase 2 in the prefrontal cortex of PTN-/- mice, suggesting that the correlation between the tyrosine phosphorylation levels of aconitase 2 and magnitude of CPP extinction depends on the genotype considered. The data demonstrate that MK is a novel genetic factor that plays a role in the extinction of cocaine-induced CPP by mechanisms that may involve specific phosphorylation of striatal peroxiredoxin 6. Copyright © 2013 Elsevier B.V. All rights reserved.

Dopaminergic and serotonergic modulation of persistent behaviour in the reinforced spatial alternation model of obsessive-compulsive disorder.

PubMed

Kontis, Dimitris; Boulougouris, Vasileios; Papakosta, Vasiliki Maria; Kalogerakou, Stamatina; Papadopoulos, Socrates; Poulopoulou, Cornelia; Papadimitriou, George N; Tsaltas, Eleftheria

2008-11-01

We have proposed rewarded T-maze alternation as a model of obsessive-compulsive disorder (OCD): the serotonin agonist m-chlorophenylpiperazine (mCPP) increments persistence therein, while chronic pretreatment with selective serotonin reuptake inhibitor (SSRI fluoxetine) but not benzodiazepine or desipramine abolishes mCPP effects. However, we noted that acute SSRI administration also causes transient persistence increase, counteracted by mCPP pretreatment. This study (a) further explores the cross-tolerance between fluoxetine and mCPP and (b) extends the model by investigating its sensitivity to dopaminergic manipulations (D2, 3 agonism--quinpirole). In both experiments, baseline and drug testing were carried out under daily T-maze alternation training. Exp. 1: Matched group (n = 8) pairs of rats received one of the following 20-day pretreatments (daily intraperitoneal administration): (1) saline, (2) low-dose fluoxetine (2.5 mg/kg), (3) low-dose mCPP (0.5 mg/kg) or (4) combined fluoxetine + mCPP. One group per pretreatment then received a 4-day challenge with high-dose fluoxetine (10 mg/kg), the other with high-dose mCPP (2.5 mg/kg). Exp. 2: One group (n = 12) of rats received 20-day treatment with saline, another with quinpirole (0.5 mg/kg). Exp. 1: Saline and low-dose mCPP- or fluoxetine-pretreated animals showed significant persistence increases under both challenges, while combined low-dose fluoxetine + mCPP pretreatment afforded full protection from either challenge. Exp. 2: Quinpirole significantly increased directional persistence after 13 administration days. These results establish the sensitivity of the rewarded alternation OCD model to D2, 3 receptor activation, thereby extending its profile of pharmacological isomorphism with OCD. Furthermore, they suggest a common mechanism of action of an SSRI and a serotonin agonist in the control of directional persistence.

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL FLOOR PLAN OF OPERATING AREA HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-0640-00-279-111678. ALTERNATE ID NUMBER 8952-CPP-640-A-1. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP640). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

ARCHITECTURAL DOOR DETAILS AND SCHEDULE OF HOT PILOT PLANT (CPP-640). INL DRAWING NUMBER 200-640-00-279-111683. ALTERNATE ID NUMBER 8952-CPP-640-A-6. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting

PubMed Central

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-01-01

We report on Y3Al5O12: Ce3+ ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce3+ concentration. The luminous properties of the Y3Al5O12: Ce3+ CPP nano phosphor are improved when compared to the Y3Al5O12: Ce3+ CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce3+ CPP with an optimal Ce3+ content of 0.5 mol % shows 2733 lm/mm2 value under high power blue radiant flux density of 19.1 W/mm2. The results indicate that Y3Al5O12: Ce3+ CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications. PMID:27502730

High power laser-driven ceramic phosphor plate for outstanding efficient white light conversion in application of automotive lighting.

PubMed

Song, Young Hyun; Ji, Eun Kyung; Jeong, Byung Woo; Jung, Mong Kwon; Kim, Eun Young; Yoon, Dae Ho

2016-08-09

We report on Y3Al5O12: Ce(3+) ceramic phosphor plate (CPP) using nano phosphor for high power laser diode (LD) application for white light in automotive lighting. The prepared CPP shows improved luminous properties as a function of Ce(3+) concentration. The luminous properties of the Y3Al5O12: Ce(3+) CPP nano phosphor are improved when compared to the Y3Al5O12: Ce(3+) CPP with bulk phosphor, and hence, the luminous emittance, luminous flux, and conversion efficiency are improved. The Y3Al5O12: Ce(3+) CPP with an optimal Ce(3+) content of 0.5 mol % shows 2733 lm/mm(2) value under high power blue radiant flux density of 19.1 W/mm(2). The results indicate that Y3Al5O12: Ce(3+) CPP using nano phosphor can serve as a potential material for solid-state laser lighting in automotive applications.

Nicotine place preference in the mouse: influences of prior handling, dose and strain and attenuation by nicotinic receptor antagonists.

PubMed

Grabus, Sheri D; Martin, Billy R; Brown, Sharon E; Damaj, M Imad

2006-03-01

Although conditioned place preferences (CPPs) are seen with most abused drugs, nicotine does not always produce a preference in this design. The goals of the present experiment were to (1) examine various factors that could contribute to these inconsistent results and (2) begin to evaluate the specific nicotinic receptors involved in the nicotine CPP. The influences of prior handling, environmental habituation, and injection habituation on a nicotine CPP were first evaluated in ICR mice. Subsequently, various nicotine doses were assessed for their abilities to produce a CPP, and the effectiveness of nicotinic receptor antagonists in attenuating this preference was examined. Finally, nicotine CPPs were assessed in C57BL/6J and DBA/2J mice to examine the influence of strain in this design. Nicotine CPPs were seen in handled/environmentally habituated, but not in unhandled, ICR mice. Habituation to the injection techniques failed to strengthen the preference. In ICR mice, a CPP was seen with one intermediate dose of nicotine. This CPP was attenuated by mecamylamine and dihydro-beta-erythroidine (DHbetaE). A nicotine CPP was also seen in C57BL/6J, but not in DBA/2J, mice. Earlier handling experience and strain are important factors when evaluating a nicotine CPP in the mouse. In addition, certain nicotinic receptors underlie the nicotine CPP, indicating that this model can elucidate underlying mediators of nicotine reward.

Disequilibrium dihedral angles in dolerite sills

USGS Publications Warehouse

Holness, Marian B.; Richardson, Chris; Helz, Rosalind T.

2012-01-01

The geometry of clinopyroxene-plagioclase-plagioclase junctions in mafic rocks, measured by the median dihedral angle Θcpp, is created during solidification. In the solidifying Kilauea Iki (Hawaii) lava lake, the wider junctions between plagioclase grains are the first to be filled by pyroxene, followed by the narrower junctions. The final Θcpp, attained when all clinopyroxene-plagioclase-plagioclase junctions are formed, is 78° in the upper crust of the lake, and 85° in the lower solidification front. Θcpp in the 3.5-m-thick Traigh Bhàn na Sgùrra sill (Inner Hebrides) is everywhere 78°. In the Whin Sill (northern England, 38 m thick) and the Portal Peak sill (Antarctica, 129 m thick), Θcpp varies symmetrically, with the lowest values at the margins. The 266-m-thick Basement Sill (Antarctica) has asymmetric variation of Θcpp, attributed to a complex filling history. The chilled margins of the Basement Sill are partially texturally equilibrated, with high Θcpp. The plagioclase grain size in the two widest sills varies asymmetrically, with the coarsest rocks found in the upper third. Both Θcpp and average grain size are functions of model crystallization times. Θcpp increases from 78° to a maximum of ∼100° as the crystallization time increases from 1 to 500 yr. Because the use of grain size as a measure of crystallization time is dependent on an estimate of crystal growth rates, dihedral angles provide a more direct proxy for cooling rates in dolerites.

Multidisciplinary Cleft Palate Program at BC Children's Hospital: Are We Meeting the Standards of Care?

PubMed

Dahiya, Anita; Courtemanche, Rebecca; Courtemanche, Douglas J

2018-05-01

To characterize current Cleft Palate Program (CPP) practices and evaluate the timeliness of appointments with respect to patient age and diagnosis based on American Cleft Palate-Craniofacial Association (ACPA) population guidelines and CPP patient-specific recommendations. A retrospective review of CPP patient appointments from November 6, 2012, to March 31, 2015, was done. Data were analyzed using descriptive and inferential statistics. The study was conducted using data from the CPP at BC Children's Hospital. A total of 1214 appointments were considered in the analysis, including syndromic and nonsyndromic patients of 0 to 27 years of age. Percentage of patients meeting follow-up targets by ACPA standards and CPP team recommendations. Our results showed patients 5 years and younger or nonsyndromic were more likely to be seen on time ( P < .001). No relationship between the timeliness of an appointment and specific patient diagnoses or distance to clinic was found. With the exception of nursing (97% of appointments were on time), all disciplines had less than 45% of appointments on time with 51% of appointments meeting ACPA guidelines for timeliness and 32% of all appointments meeting CPP recommendations. Timely care for the cleft/craniofacial patient populations represents a challenge for the CPP. Although half of patients may meet the general ACPA guidelines, only 32% of patients are meeting the CPP patient-specific recommendations. To provide better patient care, future adjustments are needed, which may include improved resource allotment and program support.

The Selective D3 Receptor Antagonist SB277011A Attenuates Morphine-Triggered Reactivation of Expression of Cocaine-Induced Conditioned Place Preference

PubMed Central

Rice, Onarae V.; Heidbreder, Christian A.; Gardner, Eliot L.; Schonhar, Charles D.; Ashby, Charles R.

2014-01-01

We examined the effect of acute administration of the selective D3 receptor antagonist SB277011A on morphine-triggered reactivation of cocaine-induced conditioned place preference (CPP) in adult male Sprague-Dawley rats. Repeated pairing of animals with 15 mg/kg i.p. of cocaine HCl or vehicle to cue-specific CPP chambers produced a significant CPP response compared to animals paired only with vehicle in both chambers. Expression of the CPP response to cocaine was then extinguished by repeatedly giving the animals vehicle injections in the cocaine-paired chambers. The magnitude of the CPP response after extinction was not significantly different from that of animals paired only with vehicle. Expression of the extinguished CPP response was reactivated by acute administration of 5 mg/kg i.p. of morphine but not by vehicle. Acute administration of 6 or 12 mg/kg i.p. (but not 3 mg/kg) of SB277011A significantly attenuated morphine-triggered reactivation of the cocaine-induced CPP. SB277011A itself (12 mg/kg i.p.) did not reactivate the extinguished CPP response. Overall, SB277011 decreases the incentive motivational actions of morphine. The present findings suggest that central D3 dopamine receptors are involved in relapse to cocaine-seeking behavior that a final common neural mechanism exists to mediate the incentive motivational effects of psychostimulants and opiates, and that selective dopamine D3 receptor antagonists constitute promising compounds for treating addiction. PMID:23404528

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP627) AND HOT PILOT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION OF REMOTE ANALYTICAL FACILITY (CPP-627) AND HOT PILOT PLANT (CPP-640) LOOKING NORTHEAST. INL PHOTO NUMBER HD-22-2-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING SOUTH AFTER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING SOUTH AFTER REMOTE ANALYTICAL FACILITY (CPP-627) WAS REMOVED. PHOTO NUMBER HD-54-33-2. Mike Crane, Photographer, 7/2006 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) ON THE RIGHT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) ON THE RIGHT AND LABORATORY (CPP-602) ON THE LEFT. INL PHOTO NUMBER NRTS-51-3373. Unknown Photographer, 9/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

PLOT PLAN OF FUEL STORAGE BUILDING (CPP603) SHOWING STORAGE BASINS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

PLOT PLAN OF FUEL STORAGE BUILDING (CPP-603) SHOWING STORAGE BASINS AND PROPOSED LOCATION OF FUEL ELEMENT CUTTING FACILITY. INL DRAWING NUMBER 200-0603-00-706-051287. ALTERNATE ID NUMBER CPP-C-1287. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP627) LOOKING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627) LOOKING SOUTHEAST. HEADEND PLANT (CPP-640) APPEARS IN THE BACKGROUND. INL PHOTO NUMBER HD-22-1-4. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. MAINTENANCE ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. MAINTENANCE SHOP AND OFFICE BUILDING (CPP-630) ON RIGHT IN PHOTO. INL PHOTO NUMBER HD-22-3-2. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Entropy as an indicator of cerebral perfusion in patients with increased intracranial pressure.

PubMed

Khan, James; Mariappan, Ramamani; Venkatraghavan, Lashmi

2014-07-01

Changes in electroencephalogram (EEG) patterns correlate well with changes in cerebral perfusion pressure (CPP) and hence entropy and bispectral index values may also correlate with CPP. To highlight the potential application of entropy, an EEG-based anesthetic depth monitor, on indicating cerebral perfusion in patients with increased intracranial pressure (ICP), we report two cases of emergency neurosurgical procedure in patients with raised ICP where anesthesia was titrated to entropy values and the entropy values suddenly increased after cranial decompression, reflecting the increase in CPP. Maintaining systemic blood pressure in order to maintain the CPP is the anesthetic goal while managing patients with raised ICP. EEG-based anesthetic depth monitors may hold valuable information on guiding anesthetic management in patients with decreased CPP for better neurological outcome.

Toward global standards for comparator pharmaceutical products: case studies of amoxicillin, metronidazole, and zidovudine in the Americas.

PubMed

Löbenberg, Raimar; Chacra, Nadia B; Stippler, Erika S; Shah, Vinod P; DeStefano, Anthony J; Hauck, Walter W; Williams, Roger L

2012-09-01

This study compared in vitro dissolution characteristics and other quality measures of different amoxicillin, metronidazole, and zidovudine products purchased in the Americas to a comparator pharmaceutical product (CPP). These three drugs are classified as Biopharmaceutics Classification System Class I drugs with the possibility that dissolution findings might be used to document bioequivalence. All investigated zidovudine products were found to be in vitro equivalent to the CPP. Only 3 of 12 tested amoxicillin products were found to be in vitro equivalent to the CPP. None of the tested metronidazole products were in vitro equivalent to the CPP. These findings suggest but do not confirm bioinequivalence where in vitro comparisons failed, given that an in vivo blood level study might have confirmed bioequivalence. At times, identifying a CPP in one of the selected markets proved difficult. The study demonstrates that products sold across national markets may not be bioequivalent. When coupled with the challenge of identifying a CPP in different countries, the results of this study suggest the value of an international CPP as well as increased use of BCS approaches as means of either documenting bioequivalence or signaling the need for further in vivo studies. Because of increased movement of medicines across national borders, practitioners and patients would benefit from these approaches.

Baclofen blocks the acquisition and expression of mitragynine-induced conditioned place preference in rats.

PubMed

Yusoff, Nurul H M; Mansor, Sharif M; Müller, Christian P; Hassan, Zurina

2018-06-01

Mitragynine is the major alkaloid found in the leaves of M. speciosa Korth (Rubiaceae), a plant that is native to Southeast Asia. This compound has been used, either traditionally or recreationally, due to its psychostimulant and opioid-like effects. Recently, mitragynine has been shown to exert conditioned place preference (CPP), indicating the rewarding and motivational properties of M. speciosa. Here, the involvement of GABA B receptors in mediating mitragynine reward is studied using a CPP paradigm in rats. First, we examined the effects of GABA B receptor agonist baclofen (1.25, 2.5 and 5 mg/kg) on the acquisition of mitragynine (10 mg/kg)-induced CPP. Second, the involvement of GABA B receptors in the expression of mitragynine-induced CPP was tested. We found that the acquisition of mitragynine-induced CPP could be blocked by higher doses (2.5 and 5 mg/kg) of baclofen. Baclofen at a high dose inhibited locomotor activity and caused a CPP. Furthermore, we found that baclofen (2.5 and 5 mg/kg) also blocked the expression of mitragynine-induced CPP. These findings suggest that both, the acquisition and expression of mitragynine's reinforcing properties is controlled by the GABA B receptor. Copyright © 2018 Elsevier B.V. All rights reserved.

Ayahuasca and Its DMT- and β-carbolines - Containing Ingredients Block the Expression of Ethanol-Induced Conditioned Place Preference in Mice: Role of the Treatment Environment.

PubMed

Cata-Preta, Elisangela G; Serra, Yasmim A; Moreira-Junior, Eliseu da C; Reis, Henrique S; Kisaki, Natali D; Libarino-Santos, Matheus; Silva, Raiany R R; Barros-Santos, Thaísa; Santos, Lucas C; Barbosa, Paulo C R; Costa, José L; Oliveira-Lima, Alexandre J; Berro, Lais F; Marinho, Eduardo A V

2018-01-01

Ayahuasca is a hallucinogenic beverage produced from the decoction of Banisteriopsis caapi (Bc) and Psychotria viridis (Pv), β-carboline- and N,N -dimethyltryptamine(DMT)-containing plants, respectively. Accumulating evidence suggests that ayahuasca may have therapeutic effects on ethanol abuse. It is not known, however, whether its effects are dependent on the presence of DMT or if non-DMT-containing components would have therapeutic effects. The aim of the present study was to investigate the rewarding properties of ayahuasca (30, 100, and 300 mg/kg, orally), Bc (132, 440, and 1320 mg/kg, orally) and Pv (3.75, 12.5 and 37.5 mg/kg, i.p.) extracts and their effects on ethanol (1.8 g/kg, i.p.) reward using the conditioned place preference (CPP) paradigm in male mice. Animals were conditioned with ayahuasca, Bc or Pv extracts during 8 sessions. An intermediate, but not a high, dose of ayahuasca induced CPP in mice. Bc and Pv did not induce CPP. Subsequently, the effects of those extracts were tested on the development of ethanol-induced CPP. Ayahuasca, Bc or Pv were administered before ethanol injections during conditioning sessions. While Bc and Pv exerted no effects on ethanol-induced CPP, pretreatment with ayahuasca blocked the development of CPP to ethanol. Finally, the effects of a post-ethanol-conditioning treatment with ayahuasca, Bc or Pv on the expression of ethanol-induced CPP were tested. Animals were conditioned with ethanol, and subsequently treated with either ayahuasca, Bc or Pv in the CPP environment previously associated with saline or ethanol for 6 days. Animals were then reexposed to ethanol and ethanol-induced CPP was quantified on the following day. Treatment with all compounds in the ethanol-paired environment blocked the expression of ethanol-induced CPP. Administration of an intermediate, but not a high, dose of ayahuasca and Bc, as well as Pv administration, in the saline-paired compartment blocked the expression of ethanol-induced CPP. The present study sheds light into the components underlying the therapeutic effects of ayahuasca on ethanol abuse, indicating that ayahuasca and its plant components can decrease ethanol reward at doses that do not exert abuse liability. Importantly, the treatment environment seems to influence the therapeutic effects of ayahuasca and Bc, providing important insights into clinical practice.

Mortality and Outcome Comparison Between Brain Tissue Oxygen Combined with Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy and Intracranial Pressure/Cerebral Perfusion Pressure-Guided Therapy in Traumatic Brain Injury: A Meta-Analysis.

PubMed

Xie, Qiang; Wu, Hai-Bing; Yan, Yu-Feng; Liu, Meng; Wang, Er-Song

2017-04-01

The combination of brain tissue oxygen and standard intracranial pressure (ICP)/cerebral perfusion pressure (CPP)-guided therapy is thought to improve traumatic brain injury (TBI) prognosis compared with standard ICP/CPP-guided therapy. However, related results of previous observational studies and recently published cohort studies and randomized controlled trials (RCTs) remain controversial. The objective of this study was to compare the effect of the combined therapy with that of standard ICP/CPP-guided therapy on mortality rate, favorable outcome, ICP/CPP, and length of stay (LOS). We systematically searched PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and Web of Science in July 2016 for studies comparing the combined therapy and standard ICP/CPP-guided therapy. Random-effect and fixed-effect models were used for pooled analyses. After screening 362 studies, 8 cohort studies and 1 RCT were included. Primary outcomes were mortality and favorable outcome. The overall mortality risk ratio showed no obvious advantages between the 2 groups (risk ratio [RR], 0.76; 95% confidence interval [CI], 0.54-1.06) and discharge mortality (RR, 1.01; 95% CI, 0.80-1.26) and 3-month mortality (RR, 0.77; 95% CI, 0.53-1.12). Compared with the ICP/CPP group, the combined group was more likely to achieve better outcome during the 6 months after TBI (RR, 1.26; 95% CI, 1.04-1.52) or exactly at 6 months (RR, 1.34; 95% CI, 1.07-1.68), whereas ICP (standardized mean difference [SMD], -0.19; 95% CI, -0.43 to 0.05), CPP (SMD, 0.13; 95% CI, -0.09 to 0.35), and LOS (SMD, 0.13; 95% CI, -0.11 to 0.37) showed no obvious differences. Compared with standard ICP/CPP-guided therapy, brain tissue oxygen combined with ICP/CPP-guided therapy improved long-term outcomes without any effects on mortality, ICP/CPP, or LOS. Copyright © 2016 Elsevier Inc. All rights reserved.

Baclofen facilitates the extinction of methamphetamine-induced conditioned place preference in rats

PubMed Central

Voigt, Robin M.; Herrold, Amy A.; Napier, T. Celeste

2011-01-01

The powerful, long-lasting association between the rewarding effects of a drug and contextual cues associated with drug administration can be studied using conditioned place preference (CPP). The GABAB receptor agonist baclofen facilitates the extinction of morphine-induced CPP in mice. The current study extended this work by determining if baclofen could enhance the extinction of methamphetamine (Meth) CPP. CPP was established using a six day conditioning protocol wherein Meth-pairings were alternated with saline-pairings. Rats were subsequently administered baclofen (2mg/kg i.p. or vehicle) immediately after each daily forced extinction session, which consisted of a saline injection immediately prior to being placed into the previously Meth- or saline-paired chamber. One extinction training cycle, consisted of six once-daily forced extinction sessions, mimicking the alternating procedure established during conditioning, followed by a test for preference (Ext test). CPP persisted for at least four extinction cycles in vehicle-treated rats. In contrast, CPP was inhibited following a single extinction training cycle. These data indicate that Meth-induced CPP was resistant to extinction, but extinction training was rendered effective when the training was combined with baclofen. These findings converge with the prior demonstration of baclofen facilitating the extinction of morphine-induced CPP indicating that GABAB receptor actions are independent of the primary (unconditioned) stimulus (i.e., the opiate or the stimulant) and likely reflect mechanisms engaged by extinction learning processes per se. Thus, baclofen administered in conjunction with extinction training may be of value for addiction therapy regardless of the class of drug being abused. PMID:21463025

Naloxone effects on extinction of ethanol- and cocaine-induced conditioned place preference in mice.

PubMed

Font, Laura; Houck, Christa A; Cunningham, Christopher L

2017-09-01

Previous studies found that naloxone (NLX) facilitated choice extinction of ethanol conditioned place preference (CPP) using long (60 min) test sessions, but there is little information on the variables determining this effect. These studies examined repeated exposure to NLX during extinction of ethanol- or cocaine-induced CPP using both short and long tests. DBA/2J mice were injected with NLX (0 or 10 mg/kg) before three 10- or 60-min choice extinction tests (experiment 1). All mice received a final 60-min test without NLX. Post-test NLX was given in experiment 2. Experiment 3 tested whether NLX would affect a forced extinction procedure. Experiment 4 tested its effect on extinction of cocaine-induced CPP. Pre-test (but not post-test) injections of NLX-facilitated choice extinction of ethanol CPP at both test durations. Pre-test NLX also facilitated forced extinction. However, pre-test NLX had no effect on choice extinction of cocaine CPP. Extinction test duration is not critical for engaging the opioid system during ethanol CPP extinction (experiment 1). Moreover, NLX's effect does not depend on CPP expression during extinction, just exposure to previously conditioned cues (experiment 3). The null effect of post-test NLX eliminates a memory consolidation interpretation (experiment 2) and the failure to alter cocaine CPP extinction argues against alteration of general learning or memory processes (experiment 4). Overall, these data suggest that the endogenous opioid system mediates a conditioned motivational effect that normally maintains alcohol-induced seeking behavior, which may underlie the efficacy of opiate antagonists in the treatment of alcoholism.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses

PubMed Central

Pildervasser, João V. N.; Abrahao, Karina P.; Souza-Formigoni, Maria L. O.

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties. PMID:25152719

Effects of a Rhodiola rosea L. extract on the acquisition, expression, extinction, and reinstatement of morphine-induced conditioned place preference in mice.

PubMed

Mattioli, Laura; Titomanlio, Federica; Perfumi, Marina

2012-05-01

Opioid addiction is a chronic, recurrent brain disease that is characterised by compulsive drug seeking and a high rate of relapse even after long periods of abstinence. Prevention of relapse is the primary goal of addiction treatment and is still the major limitation in drug therapy. The present study investigated the effects of a Rhodiola rosea L. hydroalcoholic extract (RHO), a well-known traditional oriental medicine, on establishment and reinstatement of morphine-induced conditioned place preference (CPP) in mice. CPP was induced by intraperitoneal injection of morphine (10 mg/kg) as an 8-day conditioning schedule. The effects of RHO on the rewarding properties of morphine were tested in mice receiving oral administration of RHO (10, 15, and 20 mg/kg) 60 min prior to each morphine injection (acquisition) or prior to the CPP test on day 9 (expression). Once established, CPP was extinguished by repeated testing, during which conditioned mice were injected daily with different doses of RHO. Finally, the efficacy of RHO in blocking reinstatement of CPP provoked by priming injections and physical stress was also evaluated. RHO administration showed dose dependency for prevention of establishment of CPP and was effective in facilitating extinction of morphine-induced CPP. RHO suppressed both priming- and stress-induced reinstatement of CPP in a dose-dependent manner. In conclusion, as RHO was effective for reducing craving and vulnerability to relapse, it might be a very effective natural remedy for the treatment of opioid addiction.

Glomeruloid Microvascular Proliferation, Desmoplasia, and High Proliferative Index as Potential Indicators of High Grade Canine Choroid Plexus Tumors.

PubMed

Muscatello, Luisa Vera; Avallone, Giancarlo; Serra, Fabienne; Seuberlich, Torsten; Mandara, Maria Teresa; Sisó, Silvia; Brunetti, Barbara; Oevermann, Anna

2018-05-01

Choroid plexus tumors (CPT) are intraventricular neoplasms accounting for 10% of all primary central nervous system tumors in dogs. They are frequently classified according to the human WHO classification into choroid plexus papilloma (CPP, grade I), atypical CPP (aCPP, grade II), and choroid plexus carcinoma (CPC, grade III). Histological features observed in canine CPT such as increased vascular density (IVD) and glomeruloid microvascular proliferation (GMVP) are not part of the WHO classification. This multi-centric study aimed to investigate tumor-associated vascular hyperplasia in dogs by determining the prevalence of GMVP and IVD in 52 canine CPT and their association with tumor grade. In addition, the expression of angiogenic factors was assessed by immunohistochemistry in 25 tumors to investigate the pathogenesis of tumor-associated vascular hyperplasia. Based on the classical histological hallmarks, this study of 52 CPT identified 22 (42%) CPP (grade I) and 30 of (58%) CPC (grade III). GMVP was more prevalent in CPC (13/30; 43%) than CPP (1/22; 4%), whereas IVD occurred to a similar extent in CPP and CPC. Desmoplasia was more common in CPC (19/30; 63%) than CPP (2/22; 9%), and similarly, the proliferative index (PI) of neoplastic epithelium was significantly higher in CPC (5.14%) than CPP (0.94%). The majority of CPT expressed platelet-derived growth factor (PDGF), PDGFRα, PDGFRβ, and vascular endothelial growth factor (VEGF) irrespective of tumor grade or tumor-associated vascular hyperplasia. These results suggest that tumor-associated GMVP, desmoplasia, and PI may serve as histological indicators of malignancy in CPT.

Distinct behavioral phenotypes in ethanol-induced place preference are associated with different extinction and reinstatement but not behavioral sensitization responses.

PubMed

Pildervasser, João V N; Abrahao, Karina P; Souza-Formigoni, Maria L O

2014-01-01

Conditioned place preference (CPP) is a model to study the role of drug conditioning properties. In outbred strains, individual variability may affect some behavioral measures. However, there are few studies focusing on understanding how different phenotypes of ethanol conditioned behavior may influence its extinction, reinstatement, and behavioral adaptation measures. We used male Swiss Webster mice to study different phenotypes related to ethanol conditioning strength, reinstatement and behavioral sensitization. Mice went through a CPP procedure with ethanol (2.2 g/kg, i.p.). After that, one group of mice was submitted to repeated extinction sessions, while another group remained in their home cages without any drug treatment. Mice went through environmental and ethanol priming (1.0 g/kg, i.p.) reinstatement tests. Ethanol priming test reinstated the conditioned behavior only in the animals kept in the home-cage during the abstinence period. Besides, the ethanol conditioned behavior strength was positively correlated with the time required to be extinguished. In the second set of experiments, some mice went through a CPP protocol followed by behavioral sensitization (five i.p. administrations of ethanol 2.2 g/kg or saline per week, for 3 weeks) and another group of mice went through sensitization followed by CPP. No positive correlation was observed between ethanol CPP strength and the intensity of behavioral sensitization. Considering that different phenotypes observed in CPP strength predicted the variability in other CPP measures, we developed a statistics-based method to classify mice according to CPP strength to be used in the evaluation of ethanol conditioning properties.

Topical Delivery of Anti-VEGF Drugs to the Ocular Posterior Segment Using Cell-Penetrating Peptides.

PubMed

de Cogan, Felicity; Hill, Lisa J; Lynch, Aisling; Morgan-Warren, Peter J; Lechner, Judith; Berwick, Matthew R; Peacock, Anna F A; Chen, Mei; Scott, Robert A H; Xu, Heping; Logan, Ann

2017-05-01

To evaluate the efficacy of anti-VEGF agents for treating choroidal neovascularization (CNV) when delivered topically using novel cell-penetrating peptides (CPPs) compared with delivery by intravitreal (ivit) injection. CPP toxicity was investigated in cell cultures. Ivit concentrations of ranibizumab and bevacizumab after topical administration were measured using ELISA. The biological efficacy of topical anti-VEGF + CPP complexes was compared with ivit anti-VEGF injections using an established model of CNV. CPPs were nontoxic in vitro. In vivo, after topical eye drop delivery, CPPs were present in the rat anterior chamber within 6 minutes. A single application of CPP + bevacizumab eye drop delivered clinically relevant concentrations of bevacizumab to the posterior chamber of the rat eye in vivo. Similarly, clinically relevant levels of CPP + ranibizumab and CPP + bevacizumab were detected in the porcine vitreous and retina ex vivo. In an established model of CNV, mice treated with either a single ivit injection of anti-VEGF, twice daily CPP + anti-VEGF eye drops or daily dexamethasone gavage for 10 days all had significantly reduced areas of CNV when compared with lasered eyes without treatment. CPPs are nontoxic to ocular cells and can be used to deliver therapeutically relevant doses of ranibizumab and bevacizumab by eye drop to the posterior segment of mouse, rat, and pig eyes. The CPP + anti-VEGF drug complexes were cleared from the retina within 24 hours, suggesting a daily eye drop dosing regimen. Daily, topically delivered anti-VEGF with CPP was as efficacious as a single ivit injection of anti-VEGF in reducing areas of CNV in vivo.

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP627) ADJOINING FUEL PROCESSING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

AERIAL SHOWING COMPLETED REMOTE ANALYTICAL FACILITY (CPP-627) ADJOINING FUEL PROCESSING BUILDING AND EXCAVATION FOR HOT PILOT PLANT TO RIGHT (CPP-640). INL PHOTO NUMBER NRTS-60-1221. J. Anderson, Photographer, 3/22/1960 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP601) ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH SECTION OF WEST ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. HEADEND PLANT BUILDING (CPP-640) APPEARS ON LEFT IN PHOTO. INL PHOTO NUMBER HD-22-3-3. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

The role of ovarian hormones in sexual reward states of the female rat.

PubMed

Parada, Mayte; Vargas, Erica Barbosa; Kyres, Maria; Burnside, Kimberly; Pfaus, James G

2012-09-01

To what extent does the reward value of sexual stimulation in females depend on ovarian hormones? The effects of estradiol benzoate (EB) and progesterone (P) were examined on the acquisition and expression of sexual reward induced by paced copulation and clitoral stimulation (CLS) in ovariectomized (OVX) rats. In experiment 1 we examined the expression of a pacing-induced conditioned place preference (CPP). Ovariectomized, hormone-primed rats were given experience with paced copulation associated with one side of a CPP apparatus. Changing hormonal status prior to the final CPP test did not alter pacing-induced CPP. However, subsequent partial extinction of CPP was observed only in rats primed with EB+P, a treatment previously shown to induce sexual desire and receptivity. In Experiment 2, significant CLS-induced CPP developed in ovariectomized rats regardless of hormone priming. Our results show that the expression of the sexual reward state induced by paced copulation, and CLS in particular, is independent of hormone priming. We propose that ovarian hormones sensitize sensory and motor pathways necessary for sexual behavior and stimulation to induce reward. Copyright © 2012 Elsevier Inc. All rights reserved.

Referred Pain Patterns Provoked on Intra-Pelvic Structures among Women with and without Chronic Pelvic Pain: A Descriptive Study

PubMed Central

Butler, Stephen; Peterson, Magnus; Eriksson, Margaretha

2015-01-01

Objectives To describe referred pain patterns provoked from intra-pelvic structures in women with chronic pelvic pain (CPP) persisting after childbirth with the purpose to improve diagnostics and give implications for treatment. Materials and Methods In this descriptive and comparative study 36 parous women with CPP were recruited from a physiotherapy department waiting list and by advertisements in newspapers. A control group of 29 parous women without CPP was consecutively assessed for eligibility from a midwifery surgery. Inclusion criterion for CPP was: moderate pain in the sacral region persisting at least six months after childbirth confirmed by pelvic pain provocation tests. Exclusion criteria in groups with and without CPP were: persistent back or pelvic pain with onset prior to pregnancy, previous back surgery and positive neurological signs. Pain was provoked by palpation of 13 predetermined intra-pelvic anatomical landmarks. The referred pain distribution was expressed in pain drawings and described in pain maps and calculated referred pain areas. Results Pain provoked by palpation of the posterior intra-pelvic landmarks was mostly referred to the sacral region and pain provoked by palpation of the ischial and pubic bones was mostly referred to the groin and pubic regions, with or without pain referred down the ipsilateral leg. The average pain distribution area provoked by palpation of all 13 anatomical landmarks was 30.3 mm² (19.2 to 53.7) in women with CPP as compared to 3.2 mm² (1.0 to 5.1) in women without CPP, p< 0.0001. Conclusions Referred pain patterns provoked from intra-pelvic landmarks in women with CPP are consistent with sclerotomal sensory innervation. Magnification of referred pain patterns indicates allodynia and central sensitization. The results suggest that pain mapping can be used to evaluate and confirm the pain experience among women with CPP and contribute to diagnosis. PMID:25793999

Partial extinction of a conditioned context enhances preference for elements previously associated with cocaine but not with chocolate.

PubMed

Orsini, C; Bonito-Oliva, A; Montanari, C; Conversi, D; Cabib, S

2013-08-15

Drug-associated stimuli are crucial to reinstatement of drug-seeking after periods of abstinence, representing a central problem in treatment of addiction. The present study investigated the influence of partial extinction of the conditioned context on the expression of conditioned place preference (CPP). Mice of the inbred DBA/2J strain were conditioned with cocaine or chocolate in a context identified by multiple elements (A+B) and subsequently CPP expression was evaluated in a context containing only one element (A or B) or both (A+B). Cocaine- and chocolate-conditioned mice showed CPP in presence of the original compound stimulus. However, cocaine-conditioned mice did not show CPP when tested in A or B context, while chocolate-conditioned mice did show CPP to single element context. After conditioning mice were exposed to extinction training of the context A or B and then tested for CPP 1 and 9 days after the end of the extinction (days 9 and 18). Cocaine-conditioned mice showed CPP 9 days after extinction while chocolate-conditioned mice were relatively insensitive to the extinction procedure on day 1 after extinction, but they did not show CPP for the partial or the original compound 9 days after extinction. Cocaine-conditioned mice not submitted to the extinction training (simple passage of time) or submitted to a Sham-extinction procedure (saline injections and confinement in a new environment) did not show CPP on day 9 or 18. Cocaine-conditioned mice exposed to extinction training showed increased c-Fos expression in several brain areas in comparison to mice exposed to Sham-extinction. The extinction procedure did not specifically reduce behavioral sensitization. The results suggest that extinction training involving only elements of a drug-associated context can result in increased associative strength of those elements. © 2013.

Nicotine enhances the locomotor stimulating but not the conditioned rewarding effect of ethanol in DBA/2J mice.

PubMed

Gubner, Noah R; Cunningham, Christopher L; Phillips, Tamara J

2015-01-01

One hypothesis to explain the high rate of nicotine and alcohol (ethanol [EtOH]) co-abuse is that these drugs have enhanced rewarding effects when taken together. The goal of this work was to use the conditioned place preference (CPP) procedure to determine whether nicotine would enhance the development of EtOH-induced CPP. The conditioned rewarding effects of nicotine (1 or 2 mg/kg of nicotine tartrate), EtOH (1 g/kg), and nicotine plus EtOH in combination were assessed using a well-established CPP procedure chosen specifically for examining alterations in the development of EtOH-induced CPP by nicotine. In addition, the reference dose procedure was used to directly compare the conditioned rewarding effect of EtOH versus nicotine plus EtOH. DBA/2J mice were used because they are an inbred strain that has repeatedly been shown to develop CPP to EtOH. Neither dose of nicotine alone produced CPP, whereas EtOH did, using the standard EtOH CPP procedure. The magnitude of EtOH-induced CPP was not affected by co-administration of 1 mg/kg nicotine, but 2 mg/kg nicotine interfered with the development of EtOH-induced CPP. Using the reference dose procedure, there was no significant preference or aversion for either nicotine + EtOH dose combination versus EtOH alone. However, combined nicotine and EtOH had a larger effect on locomotor activity, during the conditioning trials, compared to their additive effect when given alone, consistent with previous data. These data do not support the hypothesis that nicotine enhances the conditioned rewarding effect of EtOH. This finding differs from the combined locomotor stimulant effects of nicotine and EtOH that were observed in this study and in our previously published work, and suggests that combined stimulant effects of nicotine and EtOH do not predict enhanced reward. Copyright © 2015 by the Research Society on Alcoholism.

Evaluation of rainfall retrievals from SEVIRI reflectances over West Africa using TRMM-PR and CMORPH

NASA Astrophysics Data System (ADS)

Wolters, E. L. A.; van den Hurk, B. J. J. M.; Roebeling, R. A.

2011-02-01

This paper describes the evaluation of the KNMI Cloud Physical Properties - Precipitation Properties (CPP-PP) algorithm over West Africa. The algorithm combines condensed water path (CWP), cloud phase (CPH), cloud particle effective radius (re), and cloud-top temperature (CTT) retrievals from visible, near-infrared and thermal infrared observations of the Spinning Enhanced Visible and Infrared Imager (SEVIRI) onboard the Meteosat Second Generation (MSG) satellites to estimate rain occurrence frequency and rain rate. For the 2005 and 2006 monsoon seasons, it is investigated whether the CPP-PP algorithm is capable of retrieving rain occurrence frequency and rain rate over West Africa with sufficient accuracy, using Tropical Monsoon Measurement Mission Precipitation Radar (TRMM-PR) as reference. As a second goal, it is assessed whether SEVIRI is capable of monitoring the seasonal and daytime evolution of rainfall during the West African monsoon (WAM), using Climate Prediction Center Morphing Technique (CMORPH) rainfall observations. The SEVIRI-detected rainfall area agrees well with TRMM-PR, with the areal extent of rainfall by SEVIRI being ~10% larger than from TRMM-PR. The mean retrieved rain rate from CPP-PP is about 8% higher than from TRMM-PR. Examination of the TRMM-PR and CPP-PP cumulative frequency distributions revealed that differences between CPP-PP and TRMM-PR are generally within +/-10%. Relative to the AMMA rain gauge observations, CPP-PP shows very good agreement up to 5 mm h-1. However, at higher rain rates (5-16 mm h-1) CPP-PP overestimates compared to the rain gauges. With respect to the second goal of this paper, it was shown that both the accumulated precipitation and the seasonal progression of rainfall throughout the WAM is in good agreement with CMORPH, although CPP-PP retrieves higher amounts in the coastal region of West Africa. Using latitudinal Hovmüller diagrams, a fair correspondence between CPP-PP and CMORPH was found, which is reflected by high correlation coefficients (~0.7) for both rain rate and rain occurrence frequency. The daytime cycle of rainfall from CPP-PP shows distinctly different patterns for three different regions in West Africa throughout the WAM, with a decrease in dynamical range of rainfall near the Inter Tropical Convergence Zone (ITCZ). The dynamical range as retrieved from CPP-PP is larger than that from CMORPH. It is suggested that this results from both the better spatio-temporal resolution of SEVIRI, as well as from thermal infrared radiances being partly used by CMORPH, which likely smoothes the daytime precipitation signal, especially in case of cold anvils from convective systems. The promising results show that the CPP-PP algorithm, taking advantage of the high spatio-temporal resolution of SEVIRI, is of added value for monitoring daytime precipitation patterns in tropical areas.

Comparative evaluation of remineralization potential of casein phosphopeptide-amorphous calcium phosphate and casein phosphopeptide-amorphous calcium phosphate fluoride on artificial enamel white spot lesion: an in vitro light fluorescence study.

PubMed

Mehta, R; Nandlal, B; Prashanth, S

2013-01-01

World-wide, the contribution of dental caries to the burden of oral diseases is about 10 times higher than that of periodontal disease, the other common oral condition. Owing to its globally high prevalence, dental caries is a "pandemic" disease characterized by a high percentage of untreated carious cavities causing pain, discomfort and functional limitations. Untreated carious cavities; furthermore, have a significant impact on the general health of children and on the social and economic well-being of communities. A surgical approach to the elimination of carious lesion was developed a century ago; this approach was necessary at that time, because there was no valid alternative. The focus in caries has recently shifted to the development of methodologies for the detection of the early stages of caries lesions and the non-invasive treatment of these lesions. The non-invasive treatment of early lesions by remineralization has the potential to be a major advance in the clinical management of the disease. Remineralization of white-spot lesions may be possible with a variety of currently available agents containing fluoride, bioavailable calcium and phosphate and phosphate. This concept bridges the traditional gap between prevention and surgical procedures, which is just what dentistry needs today. The aim of this in vitro study was to evaluate and to compare the remineralization potential of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) and casein phosphopeptide-amorphous calcium fluoride phosphate (CPP-ACFP) on artificial white spot enamel lesions using the quantitative light fluorescence (QLF). A total of 45 caries-free extracted maxillary first premolars were embedded in acrylic resin. The samples were randomly divided into three groups namely control group, CPP-ACP group and CPP-ACFP group with 15 samples in each group. The samples of each group were subjected to demineralization process for a period of 96 h. The samples were then mounted in the artificial mouth model and subjected to remineralization and pH cycling for a period of 21 days. QLF readings were recorded at the end of demineralization (1st, 7th, 14th and 21st day) and were statistically analyzed. As compared with artificial saliva both CPP-ACP and CPP-ACFP produced significant amount of remineralization of the artificial enamel white spot lesion (P < 0.001), however when the remineralizing effect of CPP-ACP was compared with the remineralizing effect of CPP-ACFP there was no significant difference. Significant amount of remineralization was produced by CPP-ACP and CPP-ACFP only after the 7th day. After the 14th day, the remineralization produced by both CPP-ACP and CPP-ACFP as compared to artificial saliva was non-significant.

Involvement of NMDA glutamate receptors in the acquisition and reinstatement of the conditioned place preference induced by MDMA.

PubMed

García-Pardo, Maria P; Escobar-Valero, Carla; Rodríguez-Arias, Marta; Miñarro, Jose; Aguilar, Maria A

2015-08-01

Some 3,4-methylenedioxymethamphetamine (MDMA) users become dependent as a result of chronic consumption. A greater understanding of the neurobiological basis of the rewarding effects of MDMA could contribute to developing effective pharmacotherapies for MDMA-related problems. The present study evaluated the role of N-methyl-D-aspartate (NMDA) glutamate receptors (NMDARs) in the acquisition and reinstatement of conditioned place preference (CPP) induced by MDMA. Adolescent male mice were conditioned with 1 or 10 mg/kg MDMA and pretreated with 5 or 10 mg/kg of the NMDAR antagonist memantine during acquisition of conditioning (experiment 1), or before a reinstatement test (experiment 2). In addition, the effects of memantine on acquisition of chocolate-induced CPP and the effects of memantine and MDMA on a passive avoidance task were evaluated. Memantine did not exert any motivational effects, but blocked the acquisition of MDMA-induced CPP. Moreover, following acquisition and extinction of MDMA-induced CPP, memantine did not induce reinstatement but blocked reinstatement of the CPP induced by priming with MDMA. Memantine did not block the CPP induced by chocolate, and it partially reversed the impairing effects of MDMA on memory. Our results demonstrate that NMDARs are involved in acquisition of the conditioned rewarding effects of MDMA and in priming-induced reinstatement of CPP following extinction. Moreover, they suggest the validity of memantine for the treatment of MDMA abuse.

Extraction optimization and influences of drying methods on antioxidant activities of polysaccharide from cup plant (Silphium perfoliatum L.)

PubMed Central

Li, Ran; Duan, Meng-Ying; Wu, Hong-Xin

2017-01-01

Response surface methodology (RSM) was used to investigate the extraction condition of polysaccharide from cup plant (Silphium perfoliatum L.) (named CPP). Water to raw material ratio (10–30 mL/g), extraction time (40–80 min) and extraction temperature (60–100°C) were set as the 3 independent variables, and their effects on the extraction yield of CPP were measured. In addition, the effects of drying methods including hot air drying (HD), vacuum drying (VD) and freeze drying (FD) on the antioxidant activities of CPP were evaluated. The results showed that the optimal condition to extract CPP was: water to raw material ratio (15 mL/g), extraction time (61 min), and extraction temperature (97°C), a maximum CPP yield of 6.49% was obtained under this condition. CPP drying with FD method showed stronger reducing power (0.943 at 6 mg/mL) and radical scavenging capacities against DPPH radical (75.71% at 1.2 mg/mL) and ABTS radical (98.06 at 1.6 mg/mL) than CPP drying with HD and VD methods. Therefore, freeze drying served as a good method for keeping the antioxidant activities of polysaccharide from cup plant. The polysaccharide from cup plant has potential to use as a natural antioxidant. PMID:28837625

DYNAMIC CEREBROVASCULAR AND INTRACRANIAL PRESSURE REACTIVITY ASSESMENT OF IMPAIRED CEREBROVASCULAR AUTOREGULATION IN INTRACRANIAL HYPERTENSION

PubMed Central

Bragin, Denis E.; Statom, Gloria; Nemoto, Edwin M.

2016-01-01

SUMMARY We previously suggested that the discrepancy between the critical cerebral perfusion pressures (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP [1] and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here we demonstrated that critical CPP, measured by induced dynamic ICP reactivity (iPRx) and cerebrovascular reactivity (CVRx), accurately identifies the critical CPP in the hypertensive rat brain which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg rise in arterial pressure was induced by bolus i.v. dopamine. iPRx and iCVRx were calculated as ΔICP/ΔMAP and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to non-nutritive microvascular shunts, tissue hypoxia and BBB leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation. PMID:27165917

The effects of exogenous CCK-8 on the acquisition and expression of morphine-induced CPP.

PubMed

Wen, Di; Cong, Bin; Ma, Chunling; Yang, Shengchang; Yu, Hailei; Ni, Zhiyu; Li, Shujin

2012-02-21

Cholecystokinin octapeptide (CCK-8) is the most potent endogenous anti-opioid peptide and regulates a variety of physiological processes. In our previous study, we found that exogenous CCK-8 attenuated naloxone-induced withdrawal symptoms, but the possible regulative effects of CCK-8 on the rewarding effects of morphine were not examined. In the present study, we aimed to determine the exact effects of exogenous CCK-8 at various doses on the rewarding action of morphine by utilizing the unbiased conditioned place preference (CPP) paradigm. We therefore examined the effects of CCK-8 on the acquisition, expression and extinction of morphine-induced CPP and on locomotor activity. The results showed that CCK-8 (0.01-1μg, i.c.v.), administered alone, induced neither CPP nor place aversion, but blocked the acquisition of CPP when administered with 10mg/kg morphine. The highest dose of CCK-8 (1μg) administered before CPP testing increased CPP and, along with lower doses (0.1μg), reduced its extinction. In addition, the highest dose (1μg) of CCK-8 suppressed locomotor activity. Our study provides the first behavioral evidence for the inhibitory effects of exogenous CCK-8 on rewarding activity and reveals significant effects of exogenous CCK-8 on various stages of place preference and the development of opioid dependence. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

Role of the ventral tegmental area in methamphetamine extinction: AMPA receptor-mediated neuroplasticity

PubMed Central

Chen, Han-Ting

2015-01-01

The molecular mechanisms underlying drug extinction remain largely unknown, although a role for medial prefrontal cortex (mPFC) glutamate neurons has been suggested. Considering that the mPFC sends glutamate efferents to the ventral tegmental area (VTA), we tested whether the VTA is involved in methamphetamine (METH) extinction via conditioned place preference (CPP). Among various METH-CPP stages, we found that the amount of phospho-GluR1/Ser845 increased in the VTA at behavioral extinction, but not the acquisition or withdrawal stage. Via surface biotinylation, we found that levels of membrane GluR1 were significantly increased during METH-CPP extinction, while no change was observed at the acquisition stage. Specifically, the number of dendritic spines in the VTA was increased at behavioral extinction, but not during acquisition. To validate the role of the mPFC in METH-CPP extinction, we lesioned the mPFC. Ibotenic acid lesioning of the mPFC did not affect METH-CPP acquisition, however, it abolished the extinction stage and reversed the enhanced phospho-GluR1/Ser845 levels as well as increases in VTA dendritic spines during METH-CPP extinction. Overall, this study demonstrates that the mPFC plays a critical role in METH-CPP extinction and identifies the VTA as an alternative target in mediating the extinction of drug conditioning. PMID:25691515

Behavioral stress may increase the rewarding valence of cocaine-associated cues through a dynorphin/kappa-opioid receptor-mediated mechanism without affecting associative learning or memory retrieval mechanisms.

PubMed

Schindler, Abigail G; Li, Shuang; Chavkin, Charles

2010-08-01

Stress exposure increases the risk of addictive drug use in human and animal models of drug addiction by mechanisms that are not completely understood. Mice subjected to repeated forced swim stress (FSS) before cocaine develop significantly greater conditioned place preference (CPP) for the drug-paired chamber than unstressed mice. Analysis of the dose dependency showed that FSS increased both the maximal CPP response and sensitivity to cocaine. To determine whether FSS potentiated CPP by enhancing associative learning mechanisms, mice were conditioned with cocaine in the absence of stress, then challenged after association was complete with the kappa-opioid receptor (KOR) agonist U50,488 or repeated FSS, before preference testing. Mice challenged with U50,488 60 min before CPP preference testing expressed significantly greater cocaine-CPP than saline-challenged mice. Potentiation by U50,488 was dose and time dependent and blocked by the KOR antagonist norbinaltorphimine (norBNI). Similarly, mice subjected to repeated FSS before the final preference test expressed significantly greater cocaine-CPP than unstressed controls, and FSS-induced potentiation was blocked by norBNI. Novel object recognition (NOR) performance was not affected by U50,488 given 60 min before assay, but was impaired when given 15 min before NOR assay, suggesting that KOR activation did not potentiate CPP by facilitating memory retrieval or expression. The results from this study show that the potentiation of cocaine-CPP by KOR activation does not result from an enhancement of associative learning mechanisms and that stress may instead enhance the rewarding valence of cocaine-associated cues by a dynorphin-dependent mechanism.

Nicotine pretreatment reduced cocaine-induced CPP and its reinstatement in a sex- and dose-related manner in adult C57BL/6J mice.

PubMed

Singh, Prableen K; Lutfy, Kabirullah

2017-08-01

Previous preclinical studies have shown that nicotine pretreatment during adolescence increases the reinforcing actions of cocaine. However, little is known about the effect of prior nicotine administration on cocaine-induced conditioned place preference (CPP) and its reinstatement in adult mice. Besides, little information is available regarding the role of sex in this cross-talk between nicotine and cocaine. Thus, we examined if nicotine administration during adulthood would differentially alter cocaine-induced CPP, its extinction and reinstatement in male versus female mice and if the dose of nicotine was important in this regard. To this end, mice were pretreated with saline or nicotine (0.25 or 1mg/kg; twice daily for seven days) and then tested for place preference before and after single and repeated conditioning with cocaine (15mg/kg). Mice were then exposed to extinction training and tested for reinstatement of CPP. Our results showed that male and female mice pretreated with saline and conditioned with cocaine each exhibited a robust CPP after a single cocaine conditioning. However, this response was blunted in mice pretreated with the lower but not higher dose of nicotine. Female mice pretreated with the lower dose nicotine also failed to show CPP after repeated conditioning. Reinstatement of cocaine-induced CPP was also blunted in these mice compared to their respective controls. Together, these results suggest that nicotine administration during adulthood exerts differential effects on cocaine-induced CPP and its reinstatement in male and female mice and the dose of nicotine is important in this regard. Copyright © 2017 Elsevier Inc. All rights reserved.

An in vitro comparison of casein phosphopeptide-amorphous calcium phosphate paste, casein phosphopeptide-amorphous calcium phosphate paste with fluoride and casein phosphopeptide-amorphous calcium phosphate varnish on the inhibition of demineralization and promotion of remineralization of enamel.

PubMed

Thakkar, Prachi Jayesh; Badakar, Chandrashekhar M; Hugar, Shivayogi M; Hallikerimath, Seema; Patel, Punit M; Shah, Parin

2017-01-01

This study aims to determine and compare the extent of inhibition of demineralization and promotion of remineralization of permanent molar enamel with and without application of three remineralizing agents. Forty extracted permanent molars were randomly divided into two groups 1 and 2, longitudinally sectioned into four and divided into subgroups A, B, C, and D. The sections were coated with nail varnish leaving a window of 3 mm × 3 mm. All sections of Group 1 were treated with their respective subgroup-specific agent: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) paste for subgroup A, CPP-amorphous calcium phosphate fluoride (ACPF) paste for subgroup B, CPP-ACPF varnish for subgroup C and subgroup D served as a control. The sections were then subjected to demineralization for 12 days following which lesional depth was measured under the stereomicroscope. All the sections of Group 2 were subjected to demineralization for 12 days, examined for lesional depth, then treated with their respective subgroup specific agents and immersed in artificial saliva for 7 days. The sections were then examined again under the stereomicroscope to measure the lesional depth. CPP-ACPF varnish caused significant inhibition of demineralization. All three agents showed significant remineralization of previously demineralized lesions. However, CPP-ACPF varnish showed the greatest remineralization, followed by CPP-ACPF paste and then CPP-ACP paste. This study shows that CPP-ACPF varnish is effective in preventing demineralization as well as promoting remineralization of enamel. Thus, it can be used as an effective preventive measure for pediatric patients where compliance with the use of tooth mousse may be questionable.

Rottlerin impairs the formation and maintenance of psychostimulant-supported memory.

PubMed

Liao, Tien You; Tzeng, Wen-Yu; Wu, Hsin-Hua; Cherng, Chianfang G; Wang, Ching-Yi; Hu, Sherry S-J; Yu, Lung

2016-04-01

Since brain proteins such as protein kinase C (PKC), brain-derived neurotrophic factor (BDNF), and mammalian target of rapamycin (mTOR) are involved in the establishment and maintenance of psychostimulant memory, we sought to determine if systemic treatment with rottlerin, a natural compound affecting all these proteins, may modulate stimulant-supported memory. Stimulant-induced conditioned place preference (CPP) was used in modeling stimulant-supported memory. Three cocaine (10 mg/kg; COC) or three methamphetamine (1 mg/kg; MA) conditioning trials reliably established the drug-induced CPP in male C57BL/6 mice. An intra-peritoneal rottlerin injection (5 mg/kg) at least 24 h prior to the first COC or first MA conditioning trial prevented the establishment of CPP. Following the establishment of the COC- or MA-induced CPP, saline conditioning trial was used to extinguish the CPP. Rottlerin (5 mg/kg, intra-peritoneal (i.p.)) administered 20 h prior to the first saline conditioning trial diminished subsequent drug- and stressor-primed reinstatement of the extinguished CPP. Rottlerin (5 mg/kg, i.p.) produced a fast-onset and long-lasting increase in hippocampal BDNF levels. However, treatment with a BDNF tropomyosin receptor kinase B (TrkB) receptor antagonist, K252a (5 μg/kg), did not affect rottlerin's suppressing effect on COC-induced CPP and treatment with 7,8-dihydroxyflavone (10 mg/kg x 6, 7,8-DHF), a selective TrkB agonist, prior to each conditioning trial did not affect COC-induced CPP. These results suggest that systemic rottlerin treatment may impair the formation of COC- and MA-supported memory. Importantly, such a treatment may advance our understanding of the underlying mechanism through which extinction training resulted in the "forgetting" of the COC- and MA-supported memory.

Influence of Betaxolol on the Methamphetamine Dependence in Mice.

PubMed

Kim, Byoung-Jo; Park, Jong-Il; Eun, Hun-Jeong; Yang, Jong-Chul

2016-05-01

The noradrenaline system is involved in the reward effects of various kinds of abused drugs. Betaxolol (BTX) is a highly selective β1-antagonist. In the present study, we evaluated the effect of BTX on methamphetamine (MAP)-induced conditioned place preference (CPP) and hyperactivity in mice. The mice (n=72) were treated with MAP or saline every other day for a total of 6 days (from day 3 to day 8; 3-times MAP and 3-times saline). Each mouse was given saline (1 mL/kg) or MAP (1 mg/kg, s.c.) or BTX (5 mg/kg, i.p.) or MAP with BTX (5 mg/kg, i.p.) 30 min prior to the administration of MAP (1 mg/kg, s.c.) every other day and paired with for 1 h (three-drug and three-saline sessions). We then compared the CPP score between the two groups. After the extinction of CPP, the mice were given BTX (5 mg/kg, i.p.) or saline (1 mL/kg) 24 h prior to a priming injection of MAP, and were then immediately tested to see whether the place preference was reinstated. The repeated administration of BTX 30 min prior to the exposure to MAP significantly reduced the development of MAP-induced CPP. When BTX was administered 24 h prior to the CPP-testing session on day 9, it also significantly attenuated the CPP, but did not result in any change of locomotor activity. In the drug-priming reinstatement study, the extinguished CPP was reinstated by a MAP (0.125 mg/kg, s.c.) injection and this was significantly attenuated by BTX. These findings suggest that BTX has a therapeutic and preventive effect on the development, expression, and drug-priming reinstatement of MAP-induced CPP.

In situ effect of a CPP-ACP chewing gum on enamel erosion associated or not with abrasion.

PubMed

de Oliveira, Andressa Feitosa Bezerra; de Oliveira Diniz, Luciana Vilar; Forte, Franklin Delano Soares; Sampaio, Fabio Correia; Ccahuana-Vásquez, Renzo Alberto; Tochukwu Amaechi, Bennett

2017-01-01

The purpose of this study is to analyze the in situ effect of a casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) chewing gum on human enamel erosion lesion associated or not with abrasion. A three-way crossover study of 7 days was conducted involving 10 volunteers subjected to the same protocol: (G1) CPP-ACP sugar-free chewing gum, (G2) regular sugar-free chewing gum without CPP-ACP, and (G3) saliva-no chewing gum. An abrasion test was included in each phase. A 3D non-contact profilometry measurement of lesion depth and surface roughness was obtained of sound and eroded surfaces. A salivary calcium concentration was determined for all volunteers. ANOVA followed by Tukey's test were used with a p < 0.05. The enamel depth and the enamel surface roughness of the CPP-ACP gum group were significantly lower than the others (ANOVA, p < 0.05). No significant differences were observed between the treatments when associated with abrasion (p > 0.05). A positive and significant correlation was seen between the lesion depth and enamel surface roughness for GI (r = 0.87, p = 0.00) and GIII (r = 0.79, p = 0.00) groups. The estimated total calcium presented in the saliva after the chewed CPP-ACP gum showed no statistical significance between the mean absorbance values at the different time collections (p > 0.05). It is demonstrated that the incorporation of the CPP-ACP into a sugar-free gum significantly increased the remineralization/protection of eroded enamel surface. The CPP-ACP added to gum may be a suitable alternative vehicle, to deliver calcium ions to saliva and therefore protecting enamel.

Basolateral amygdalar D2 receptor activation is required for the companions-exerted suppressive effect on the cocaine conditioning.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Yu, Lung; Wang, Ching-Yi

2017-01-01

The presence of companions renders decreases in cocaine-stimulated dopamine release in the nucleus accumbens and cocaine-induced conditioned place preference (CPP) magnitude. Limbic systems are widely believed to underlie the modulation of accumbal dopamine release and cocaine conditioning. Thus, this study aimed to assess whether intact basolateral nucleus of amygdala (BLA), dorsal hippocampus (DH), and dorsolateral striatum (DLS) is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Three cage mates, serving as companions, were arranged to house with the experimental mice in the cocaine conditioning compartment throughout the cocaine conditioning sessions. Approximately 1week before the conditioning procedure, intracranial ibotenic acid infusions were done in an attempt to cause excitotoxic lesions targeting bilateral BLA, DH and DLS. Albeit their BLA, DH, and DLS lesions, the lesioned mice exhibited comparable cocaine-induced CPP magnitudes compared to the intact and sham lesion controls. Bilateral BLA, but not DH or DLS, lesions abolished the companions-exerted suppressive effect on the cocaine-induced CPP. Intact mice receiving intra-BLA infusion of raclopride, a selective D2 antagonist, 30min prior to the cocaine conditioning did not exhibit the companions-exerted suppressive effect on the cocaine-induced CPP. Intra-BLA infusion of Sch23390, a selective D1 antagonist, did not affect the companions-exerted suppressive effect on the CPP. These results, taken together, prompt us to conclude that the intactness of BLA is required for the companions-exerted suppressive effect on the cocaine-induced CPP. Importantly, activation of D2 receptor in the BLA is required for such suppressive effect on the CPP. Copyright © 2016 Elsevier Inc. All rights reserved.

Multimodality Monitoring for Cerebral Perfusion Pressure Optimization in Comatose Patients with Intracerebral Hemorrhage

PubMed Central

Ko, Sang-Bae; Choi, H. Alex; Parikh, Gunjan; Helbok, Raimund; Schmidt, J. Michael; Lee, Kiwon; Badjatia, Neeraj; Claassen, Jan; Connolly, E. Sander; Mayer, Stephan A.

2011-01-01

Background and Purpose Limited data exists to recommend specific cerebral perfusion pressure (CPP) targets in patients with intracerebral hemorrhage (ICH). We sought to determine the feasibility of brain multimodality monitoring (MMM) for optimizing CPP and potentially reducing secondary brain injury after ICH. Methods We retrospectively analyzed brain MMM data targeted at perihematomal brain tissue in 18 comatose ICH patients (median monitoring: 164 hours). Physiological measures were averaged over one-hour intervals corresponding to each microdialysis sample. Metabolic crisis (MC) was defined as a lactate/pyruvate ratio (LPR) >40 with a brain glucose concentration <0.7 mmol/L. Brain tissue hypoxia (BTH) was defined as PbtO2 <15 mm Hg. Pressure reactivity index (PRx) and oxygen reactivity index (ORx) were calculated. Results Median age was 59 years, median GCS score 6, and median ICH volume was 37.5 ml. The risk of BTH, and to a lesser extent MC, increased with lower CPP values. Multivariable analyses showed that CPP <80 mm Hg was associated with a greater risk of BTH (OR 1.5, 95% CI 1.1–2.1, P=0.01) compared to CPP >100 mm Hg as a reference range. Six patients died (33%). Survivors had significantly higher CPP and PbtO2 and lower ICP values starting on post-bleed day 4, whereas LPR and PRx values were lower, indicating preservation of aerobic metabolism and pressure autoregulation. Conclusions PbtO2 monitoring can be used to identify CPP targets for optimal brain tissue oxygenation. In patients who do not undergo MMM, maintaining CPP >80 mm Hg may reduce the risk of BTH. PMID:21852615

[Structural CNS abnormalities responsible for coincidental occurrence of endocrine disorders, epilepsy and psychoneurologic disorders in children and adolescents].

PubMed

Starzyk, Jerzy; Kwiatkowski, Stanisław; Kaciński, Marek; Kroczka, Sławomir; Wójcik, Małgorzata

2010-01-01

In the population of children and adolescents, epilepsy affects 0.5-1% of individuals; approximately 3% of general population suffer from non-epileptic seizures, while endocrine disorders are several times more frequent. All of the above factors result in a relatively common non-accidental occurrence of endocrine disorders, epilepsy and neuropsychiatric disorders. However, structural central nervous system (CNS) abnormalities that cause both endocrine and neurologic disorders seem to be markedly less common. No reports addressing this problem are available in the literature. 1) Assessment of the frequency of non-coincidental occurrence of epilepsy and endocrine disorders in inpatients and outpatients with structural CSN abnormalities managed in Department Endocrinology. 2) Presentation of diagnostic and therapeutic difficulties in these patients, and 3) An attempt at defining a common etiology of both disorders. A retrospective analysis of the medical records of the patients with coincidence of endocrine disorders and epilepsy and psycho-neurologic disorders (treated in Chair and Department of Children's and Adolescents Neurology, University Children's Hospital of Krakow or in another pediatric neurology center) and with organic CNS abnormalities (treated or followed up as inpatients and outpatient of Department of Pediatric Surgery, Children's University Hospital of Krakow, was performed. The patients were selected from among several thousands of children treated as inpatients and outpatients of the Department. Various forms of symptomatic and idiopathic epilepsy and other psychoneurological disorders (disorders of behavior and emotions, obsession-compulsion syndromes, stereotypias, aggression, compulsive ideas and movements, anorexia or hypothalamic obesity) coincident with one or more endocrine disorders such as precocious or delayed puberty, multihormonal pituitary deficiency, panhypopituitarism and secondary hypothyroidism were detected in 42 patients with suprasellar arachnoid cyst (7 patients), septo-optic dysplasia (8 patients), craniopharyngioma (15 patients), glioma of the optic chiasm in neurofibromatosis type 1 (NF-1) (12 patients). There were no endocrine disorders in any of the ten patients with hamartoma of the hypothalamus and CPP. Endocrine and/ or neurological disorders did not resolve or were progressive after neurosurgery. Of 42 patients, a group of seven children representative for individual disorders was selected. In those patients, the etiology of both endocrine disorders, epilepsy and neuropsychiatric disorders was suspected to be common. 1. Various structural CNS abnormalities are the cause of concomitant epilepsy and endocrinopathy, although in some cases a direct impact of a genetic factor on the occurrence of both disorders or a mere coincidence cannot be ruled out. 2. Psychoneurological disorders usually precede the onset of endocrinopathy. 3. For this reason, MR or CT CNS imaging should be performed in any case of central neurological disorders, disorders of behavior, epilepsy, obsessive-compulsive syndrome, but also in patients with delayed psycho-motor development, delayed or accelerated growth and pubertal development. All of the above-mentioned manifestations may be symptoms of structural CNS abnormalities and their early treatment determines the child's future.

Isolated Cushing's syndrome: an unusual presentation of McCune-Albright syndrome in the neonatal period.

PubMed

Paris, Françoise; Philibert, Pascal; Lumbroso, Serge; Servant, Nadège; Kalfa, Nicolas; Sultan, Charles

2009-01-01

Cushing's syndrome (CS) may develop at any time in childhood. In the neonatal period, the major cause is the overactivation of adrenal cells within the context of McCune-Albright syndrome (MAS). The hypercorticism usually appears with other clinical signs of MAS. We report here a case of isolated neonatal CS as the initial evidence of MAS. This newborn girl was referred to our pediatric endocrine unit at the age of 3 months for hypotonia and growth retardation. Clinical examination revealed facial plethora, moon face, and swollen limbs. Laboratory data demonstrated ACTH-independent CS. Magnetic resonance imaging showed moderate bilateral adrenal hyperplasia, though more marked in the left adrenal gland, without nodules. This peripheral hypercorticism without well-defined adrenal tumor was suggestive of MAS, although no other signs like precocious puberty or café-au-lait spots were found. An activating Gsalpha gene mutation was found on DNA extracted from blood. Because MAS is a somatic disease, usually with unilateral effects, we tried to remove only the larger adrenal gland, where the mutation was demonstrated. This female newborn later developed the classical triad of MAS, reinforcing this diagnosis. Cushing's syndrome in infants, even when isolated, may suggest a diagnosis of MAS. Copyright 2009 S. Karger AG, Basel.

Direct Actions of Kisspeptins on GnRH Neurons Permit Attainment of Fertility but are Insufficient to Fully Preserve Gonadotropic Axis Activity

PubMed Central

León, Silvia; Barroso, Alexia; Vázquez, María J.; García-Galiano, David; Manfredi-Lozano, María; Ruiz-Pino, Francisco; Heras, Violeta; Romero-Ruiz, Antonio; Roa, Juan; Schutz, Günther; Kirilov, Milen; Gaytan, Francisco; Pinilla, Leonor; Tena-Sempere, Manuel

2016-01-01

Kisspeptins, ligands of the receptor, Gpr54, are potent stimulators of puberty and fertility. Yet, whether direct kisspeptin actions on GnRH neurons are sufficient for the whole repertoire of their reproductive effects remains debatable. To dissect out direct vs. indirect effects of kisspeptins on GnRH neurons in vivo, we report herein the detailed reproductive/gonadotropic characterization of a Gpr54 null mouse line with selective re-introduction of Gpr54 expression only in GnRH cells (Gpr54−/−Tg; rescued). Despite preserved fertility, adult rescued mice displayed abnormalities in gonadal microstructure, with signs of precocious ageing in females and elevated LH levels with normal-to-low testosterone secretion in males. Gpr54−/−Tg rescued mice showed also altered gonadotropin responses to negative feedback withdrawal, while luteinizing hormone responses to various gonadotropic regulators were variably affected, with partially blunted relative (but not absolute) responses to kisspeptin-10, NMDA and the agonist of tachykinin receptors, NK2R. Our data confirm that direct effects of kisspeptins on GnRH cells are sufficient to attain fertility. Yet, such direct actions appear to be insufficient to completely preserve proper functionality of gonadotropic axis, suggesting a role of kisspeptin signaling outside GnRH cells. PMID:26755241

Premature adrenarche: novel lessons from early onset androgen excess.

PubMed

Idkowiak, Jan; Lavery, Gareth G; Dhir, Vivek; Barrett, Timothy G; Stewart, Paul M; Krone, Nils; Arlt, Wiebke

2011-08-01

Adrenarche reflects the maturation of the adrenal zona reticularis resulting in increased secretion of the adrenal androgen precursor DHEA and its sulphate ester DHEAS. Premature adrenarche (PA) is defined by increased levels of DHEA and DHEAS before the age of 8 years in girls and 9 years in boys and the concurrent presence of signs of androgen action including adult-type body odour, oily skin and hair and pubic hair growth. PA is distinct from precocious puberty, which manifests with the development of secondary sexual characteristics including testicular growth and breast development. Idiopathic PA (IPA) has long been considered an extreme of normal variation, but emerging evidence links IPA to an increased risk of developing the metabolic syndrome (MS) and thus ultimately cardiovascular morbidity. Areas of controversy include the question whether IPA in girls is associated with a higher rate of progression to the polycystic ovary syndrome (PCOS) and whether low birth weight increases the risk of developing IPA. The recent discoveries of two novel monogenic causes of early onset androgen excess, apparent cortisone reductase deficiency and apparent DHEA sulphotransferase deficiency, support the notion that PA may represent a forerunner condition for PCOS. Future research including carefully designed longitudinal studies is required to address the apparent link between early onset androgen excess and the development of insulin resistance and the MS.

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia.

PubMed

Collins, Michael T; Singer, Frederick R; Eugster, Erica

2012-05-24

Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues.The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD.

McCune-Albright syndrome and the extraskeletal manifestations of fibrous dysplasia

PubMed Central

2012-01-01

Fibrous dysplasia (FD) is sometimes accompanied by extraskeletal manifestations that can include any combination of café-au-lait macules, hyperfunctioning endocrinopathies, such as gonadotropin-independent precocious puberty, hyperthyroidism, growth hormone excess, FGF23-mediated renal phosphate wasting, and/or Cushing syndrome, as well as other less common features. The combination of any of these findings, with or without FD, is known as McCune-Albright syndrome (MAS). The broad spectrum of involved tissues and the unpredictable combination of findings owe to the fact that molecular defect is due to dominant activating mutations in the widely expressed signaling protein, Gsα, and the fact these mutations arises sporadically, often times early in development, prior to gastrulation, and can distribute across many or few tissues. The complexity can be mastered by a systematic screening of potentially involved tissues and cognizance that the pattern of involved tissues is established, to some degree, in utero. Thorough testing allows the clinician to establish, often times at presentation, the full extent of the disease, and importantly as well what tissues are unaffected. Treatment and follow-up can then be focused on affected systems and a meaningful prognosis can be offered to the patient and family. The authors outline screening and treatment strategies that allow for effective management of the extraskeletal manifestations of FD. PMID:22640971

[Aqueductal stenosis in the neurofibromatosis type 1. Presentation of 19 infantile patients].

PubMed

Pascual-Castroviejo, I; Pascual-Pascual, S I; Velázquez-Fragua, R; Viaño, J; Carceller-Benito, F

To present a series of infantile patients with aqueductal stenosis associated with neurofibromatosis type 1 (NF1). Nineteen patients with ages below 16 years, 11 girls and 8 boys, with NF1 presented hydrocephalus due to aqueductal stenosis. All patients, except one who died before the imaging study was performed and was diagnosed by autopsy, were studied by pneumoencephalography (since 1965 to 1974), computerized tomography (CT) (since 1975 to 1984), magnetic resonance (MR) or MR and CT (since 1985 to 2004) (two children had been studied by pneumoencephalography some years before) most times to discard optic pathway tumor and, in few patients, because of intracranial hypertension. All patients showed three ventricular hydrocephalus with aqueductal stenosis. Eleven patients showed optic pathway tumor. One patient had a benign aqueductal tumor that impaired the normal flow of cerebrospinal fluid. Neurological features of hydrocephalus occurred very rapidly in some patients and after several years of evolution in others. Two boys showed precocious puberty. All patients were treated with shunt. In our series, aqueductal stenosis occurred in about 5% of children with NF1. Aqueductal stenosis and hydrocephalus were identified at a short age because many patients were studied suspecting optic pathway tumor. Eleven patients (about 60%) associated optic pathway tumor and aqueductal stenosis.

Comparative analyses of the influence of developmental mode on phenotypic diversification rates in shorebirds

PubMed Central

Thomas, Gavin H; Freckleton, Robert P; Székely, Tamás

2006-01-01

Phenotypic diversity is not evenly distributed across lineages. Here, we describe and apply a maximum-likelihood phylogenetic comparative method to test for different rates of phenotypic evolution between groups of the avian order Charadriiformes (shorebirds, gulls and alcids) to test the influence of a binary trait (offspring demand; semi-precocial or precocial) on rates of evolution of parental care, mating systems and secondary sexual traits. In semi-precocial species, chicks are reliant on the parents for feeding, but in precocial species the chicks feed themselves. Thus, where the parents are emancipated from feeding the young, we predict that there is an increased potential for brood desertion, and consequently for the divergence of mating systems. In addition, secondary sexual traits are predicted to evolve faster in groups with less demanding young. We found that precocial development not only allows rapid divergence of parental care and mating behaviours, but also promotes the rapid diversification of secondary sexual characters, most notably sexual size dimorphism (SSD) in body mass. Thus, less demanding offspring appear to facilitate rapid evolution of breeding systems and some sexually selected traits. PMID:16769632

Comparative analyses of the influence of developmental mode on phenotypic diversification rates in shorebirds.

PubMed

Thomas, Gavin H; Freckleton, Robert P; Székely, Tamás

2006-07-07

Phenotypic diversity is not evenly distributed across lineages. Here, we describe and apply a maximum-likelihood phylogenetic comparative method to test for different rates of phenotypic evolution between groups of the avian order Charadriiformes (shorebirds, gulls and alcids) to test the influence of a binary trait (offspring demand; semi-precocial or precocial) on rates of evolution of parental care, mating systems and secondary sexual traits. In semi-precocial species, chicks are reliant on the parents for feeding, but in precocial species the chicks feed themselves. Thus, where the parents are emancipated from feeding the young, we predict that there is an increased potential for brood desertion, and consequently for the divergence of mating systems. In addition, secondary sexual traits are predicted to evolve faster in groups with less demanding young. We found that precocial development not only allows rapid divergence of parental care and mating behaviours, but also promotes the rapid diversification of secondary sexual characters, most notably sexual size dimorphism (SSD) in body mass. Thus, less demanding offspring appear to facilitate rapid evolution of breeding systems and some sexually selected traits.

Lower baseline plasma cortisol and prolactin together with increased body temperature and higher mCPP-induced cortisol responses in men with pedophilia.

PubMed

Maes, M; van West, D; De Vos, N; Westenberg, H; Van Hunsel, F; Hendriks, D; Cosyns, P; Scharpé, S

2001-01-01

There is some evidence that hormonal and serotonergic alterations may play a role in the pathophysiology of paraphilias. The aims of the present study were to examine: 1) baseline plasma cortisol, plasma prolactin, and body temperature; and 2) cortisol, prolactin, body temperature, as well as behavioral responses to meta-chlorophenylpiperazine (mCPP) and placebo in pedophiles and normal men. Pedophiles showed significantly lower baseline plasma cortisol and prolactin concentrations and a higher body temperature than normal volunteers. The mCPP-induced cortisol responses were significantly greater in pedophiles than in normal volunteers. In normal volunteers, mCPP-induced a hyperthermic response, whereas in pedophiles no such response was observed. mCPP induced different behavioral responses in pedophiles than in normal men. In pedophiles, but not in normal men, mCPP increased the sensations "feeling dizzy, " "restless," and "strange" and decreased the sensation "feeling hungry". The results suggest that there are several serotonergic disturbances in pedophiles. It is hypothesized that the results are compatible with a decreased activity of the serotonergic presynaptic neuron and a 5-HT2 postsynaptic receptor hyperresponsivity.

Reinstatement of Morphine-Induced Conditioned Place Preference in Mice by Priming Injections

PubMed Central

Do Couto, B. Ribeiro; Aguilar, M. A.; Manzanedo, C.; Rodríguez-Arias, M.; Miñarro, J.

2003-01-01

To construct a model of relapse of drug abuse in mice, the induction, we evaluated the extinction and reinstatement of morphine-induced place preference. In Experiment 1, we examined the effects of morphine (0, 2, 3, 5, 10, 20 and 40 mg/kg) in the conditioned place preference (CPP) paradigm. Mice showed CPP with 5, 10, 20 and 40 mg/kg. In Experiment 2, we evaluated the effects of two different extinction procedures. After conditioning with 40 mg/kg of morphine, the mice underwent daily extinction sessions of 60 or 15 min of duration. CPP was extinguished after seven and nine sessions, respectively. In Experiment 3, we tested the reinstating effects of several priming doses of morphine. Mice were conditioned with 40 mg/kg of morphine and underwent the daily 15 min extinction sessions until CPP was no longer evident. Then, the effects of morphine (0, 2, 3, 5, 10, 20, 40 mg/kg, i.p.) were evaluated. CPP was reinstated by doses from 5 mg/kg upward. The results show that morphine priming injections are effective in reactivating opiateseeking behavior in mice, and thus, the CPP paradigm might be useful to investigate the mechanisms underlying relapse of drug abuse. PMID:15152982

Structural characterization and hypolipidemic effect of Cyclocarya paliurus polysaccharide in rat.

PubMed

Yang, Zhan-Wei; Ouyang, Ke-Hui; Zhao, Jing; Chen, Hui; Xiong, Lei; Wang, Wen-Jun

2016-10-01

Polysaccharide is one of the important active ingredients of Cyclocarya paliurus (Batal.) Iljinskaja leaves. The aims of this work were to analyze the structure of the polysaccharide of Cyclocarya paliurus (Batal.) Iljinskaja leaves (CPP), and to investigate the antihyperlipidemic effect of CPP on high-fat emulsion (HFE)-induced hyperlipidaemic rats. CPP, comprised of two polysaccharides with average molecular weight (Mw) of 1.35×10(5)Da and 9.34×10(3)Da, was consisted of rhamnose, arabinose, xylose, mannose, glucose and galactose in the molar ratio of 1.00:2.23:0.64:0.49:0.63:4.16. Oral administration of CPP could significantly decrease levels of serum total cholesterol (TC), triglycerides (TG) and low-density lipoprotein cholesterol (LDL-C), increase high density lipoprotein (HDL-C) in hyperlipidemic rats. CPP exerts therapeutic effects on hyperlipidaemic rats, by up-regulating expressions of adipose triglyceride lipase (ATGL) and peroxisome proliferator-activated receptor alpha (PPARα), via down-regulating fatty acid synthase (FAS) and hydroxy methylglutaryl coenzyme A reductase (HMG-CoA). This study demonstrates that CPP may be beneficial for the treatment of hyperlipidemia. Copyright © 2016 Elsevier B.V. All rights reserved.

Re-evaluation of the reward comparison hypothesis for alcohol abuse.

PubMed

He, Alan Bo-Han; Chang, Yu-Chieh; Meng, Anna Wan Yun; Huang, Andrew Chih Wei

2017-08-14

This study examined whether various doses of ethanol induced reward or aversion and then evaluated Grigson's reward comparison hypothesis (1997). Rats were given a 0.1% saccharin solution (conditioned stimulus 1 [CS1]) 15min prior to administration of a 0, 0.05, 0.125, 0.20, 0.35, or 0.50g/kg dose of ethanol (unconditioned stimulus [US]). The rats were then exposed to a paired compartment (CS2) for 30min. The low dose of 0.05g/kg ethanol did not induce conditioned suppression (i.e., conditioned taste aversion [CTA]) or conditioned place preference (CPP). The dose of 0.125g/kg ethanol induced CPP but not CTA. High doses of ethanol, including 0.35g/kg and 0.50g/kg, produced CTA but not CPP. The middle dose of 0.20g/kg ethanol simultaneously induced CTA and CPP. As a result, the reward comparison hypothesis cannot explain the present finding that the middle dose of ethanol induced CTA and CPP. Meanwhile, the high doses of ethanol induced motivationally aversive CTA but not rewarding CPP. The reward comparison hypothesis should be updated further. Copyright © 2017 Elsevier B.V. All rights reserved.

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice.

PubMed

Pandy, Vijayapandi; Khan, Yasmin

2016-11-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings.

Noni (Morinda citrifolia Linn.) fruit juice attenuates the rewarding effect of ethanol in conditioned place preference in mice

PubMed Central

Pandy, Vijayapandi; Khan, Yasmin

2016-01-01

Morinda citrifolia L. commonly known as noni or Indian mulberry belongs to the family Rubiaceae. Noni fruit juice has recently become a very popular remedy for the treatment of several diseases, including psychiatric disorders. This study aimed to investigate the anticraving effect of Tahitian Noni® Juice (TNJ) against ethanol seeking behavior in ICR male mice using the conditioned place preference (CPP) test. The CPP procedure consisted of four phases: preconditioning, conditioning, extinction, and reinstatement. During conditioning, intraperitoneal (i.p.) injections of ethanol (2 g/kg body weight (bw)) and normal saline (10 ml/kg bw) were given on alternate days for 12 days. Then, the animals were subjected to extinction trials for the next 12 days to weaken CPP. Finally, CPP was reinstated in the extinguished animals by a single low-dose priming injection of ethanol (0.4 g/kg bw, i.p.). The effect of TNJ (as a source of drinking water) on different phases of ethanol CPP in mice was studied. TNJ-treated mice showed a significant reduction in ethanol seeking behavior in the CPP test. The reference drug, acamprosate (ACAM) also showed a similar effect in the CPP test. The outcome of this study suggests that TNJ is effective in attenuating ethanol craving in mice and could be utilized for the treatment of alcohol dependence. Further clinical studies in this direction are warranted to support the present preclinical findings. PMID:27333840

Concentration of Calcium, Phosphate and Fluoride Ions in Microbial Plaque and Saliva after Using CPP-ACP Paste in 6-9 year-old Children

PubMed Central

HR, Poureslami; Ra, Hoseinifar; Re, Hoseinifar; H, Sharifi; P, Poureslami

2016-01-01

Statement of Problem: Dental caries is one of the most common chronic diseases in children. The balance between demineralization and remineralization of the decayed teeth depends on the calcium and phosphate content of the tooth surface. Therefore, if a product such as casein phospho peptides - amorphous calcium phosphate (CPP- ACP) which can significantly increase the availability of calcium and phosphate in the plaque and saliva should have an anti-caries protective effect. Objectives: The purpose of this study was to evaluate the concentration of calcium, phosphate and fluoride in the plaque and saliva of children before and after applying the CPP-ACP paste. Materials and Methods: A total of 25 children aged between 6-9 years were selected for this clinical trial study. At first, 1 ml of unstimulated saliva was collected and then 1 mg of the plaque sample was collected from the buccal surfaces of the two first primary molars on the upper jaw. In the next step, CPP-ACP paste (GC Corp, Japan) was applied on the tooth surfaces and then the plaque and saliva sampling was performed after 60 minutes. The amount of calcium ions was measured by Ion meter instrument (Metrohm Co, Swiss) and the amounts of phosphate and fluoride ions were measured by Ion Chromatography instrument (Metrohm Co, Swiss). Data were analyzed using paired t-test at a p < 0.05 level of significance. Results: There were statistically significant differences in the calcium and phosphate concentration of the saliva and plaque before and after applying the CPP-ACP paste. There were also statistically significant differences in the fluoride levels of the plaque before and after applying the CPP-ACP paste. However, there were no statistically significant differences in the fluoride levels of the saliva before and after applying the CPP-ACP paste. Conclusions: In this study, the use of the CPP-ACP paste significantly increased the fluoride levels of the plaque and the calcium and phosphate levels of both saliva and plaque. Hence, CPP-ACP paste can facilitate the remineralization of tooth surfaces and is useful for protecting the primary teeth. PMID:28959745

The effects of necrotic enteritis, aflatoxin B1, and virginiamycin on growth performance, necrotic enteritis lesion scores, and mortality in young broilers.

PubMed

Cravens, R L; Goss, G R; Chi, F; De Boer, E D; Davis, S W; Hendrix, S M; Richardson, J A; Johnston, S L

2013-08-01

The effects of increasing aflatoxin B1 concentration (0, 0.75, 1.5 mg/kg) on broilers with or without necrotic enteritis or virginiamycin were determined. In the 23-d study, 22 male Cobb 500 chicks per pen were allotted to 12 treatments (3 × 2 × 2 factorial arrangement) with 8 replications. Intestines of 5 birds per pen were examined for lesions on d 21. Birds were allowed to consume feed and water ad libitum. Aflatoxin was included in the diets from d 0. All birds received a 10× dose of coccidiosis vaccine on d 10. Pens of birds where necrotic enteritis was being induced were on Clostridium perfringens pathogen (CPP) contaminated litter from d 0. Aflatoxin decreased gain and feed intake and resulted in poorer feed:gain, increased mortality, and higher lesion scores. Inducing necrotic enteritis increased lesion scores and decreased feed intake and gain. Adding virginiamycin to the diets improved gain, feed intake, feed conversion, and decreased mortality. There was a 3-way interaction (aflatoxin × virginiamycin × CPP) on gain; increasing aflatoxin decreased gain and the effects of CPP and virginiamycin were dependent on aflatoxin concentration. In the absence of aflatoxin virginiamycin increased gain but was unable to prevent the growth suppression caused by CPP. At 0.75 mg/kg of aflatoxin virginiamycin no longer increased growth in non-CPP challenged birds but was able to increase growth in CPP-challenged birds. At the 1.5 mg/kg of aflatoxin concentration, virginiamycin increased gain in non-CPP-challenged birds but challenging birds with CPP had no effect on gain. Virginiamycin improved overall feed conversion with the greatest improvement at 1.5 mg/kg (aflatoxin × virginiamycin, P < 0.05). Aflatoxin increased lesion scores in unchallenged birds but not in challenged birds (aflatoxin × CPP, P < 0.001). Aflatoxin and necrotic enteritis decrease broiler performance and interact to decrease weight gain, virginiamycin helps improve gain in challenged birds at 0.75 mg/kg of aflatoxin, but not at 1.5 mg/kg of aflatoxin.

Nonpharmacologic and pharmacologic management of CPP crystal arthritis and BCP arthropathy and periarticular syndromes.

PubMed

Rosenthal, Ann K; Ryan, Lawrence M

2014-05-01

Calcium crystal arthritis is often unrecognized, poorly managed, and few effective therapies are available. The most common types of calcium crystals causing musculoskeletal syndromes are calcium pyrophosphate (CPP) and basic calcium phosphate (BCP). Associated syndromes have different clinical presentations and divergent management strategies. Acute CPP arthritis is treated similarly to acute gouty arthritis, whereas chronic CPP and BCP arthropathy may respond to strategies used for osteoarthritis. Calcific tendonitis is treated with a variety of interventions designed to dissolve BCP crystals. A better understanding of the causes and larger well-planned trials of current therapies will lead to improved care. Copyright © 2014 Elsevier Inc. All rights reserved.

Role of medial prefrontal cortex Narp in the extinction of morphine conditioned place preference.

PubMed

Blouin, Ashley M; Han, Sungho; Pearce, Anne M; Cheng, Kailun; Lee, Jongah J; Johnson, Alexander W; Wang, Chuansong; During, Matthew J; Holland, Peter C; Shaham, Yavin; Baraban, Jay M; Reti, Irving M

2013-01-15

Narp knockout (KO) mice demonstrate an impaired extinction of morphine conditioned place preference (CPP). Because the medial prefrontal cortex (mPFC) has been implicated in extinction learning, we tested whether Narp cells in this region play a role in the extinction of morphine CPP. We found that intracranial injections of adenoassociated virus (AAV) expressing wild-type (WT) Narp into the mPFC of Narp KO mice rescued the extinction and the injection of AAV expressing a dominant negative form of Narp (NarpN) into the mPFC of WT mice impaired the extinction of morphine CPP. These findings suggest that Narp in the mPFC mediates the extinction of morphine CPP.

Factors related to the occurrence of precocious menarche in female primary school students in Makassar

NASA Astrophysics Data System (ADS)

Renjani, Rizky Swastika; Mappaware, Nasrudin A.; Nontji, Werna; Marniati

2017-09-01

Precocious menarche currently affects 1 in 5000 girls and likely to occur as many as 10 times and possess greater risk to the emergence of cancer in women. The aim of this research is to determine the relationship of nutrition status and lipid profile with precocious menarche occurrence onstudents of primary school in Makassar city. The design of this research was cross sectional design. The samples werethe students of grades IV, V and VI who have already menarche occurrence as many as 20 studentscollected with purposive sampling. The data were analyzed with Mann Whitney U test. The results indicate that there are 17 students (85%) do not undergoprecocious menarche, normal nutrition status is 11 persons (55%), normal cholesterol levelis 12 persons (60%), and level of normal LDL = 19 persons (95%). While the respondents who undergo precocious menarche is 3 persons (15%), fat nutrition status is 9 persons (45%), cautious cholesterol level is 8 persons (40%) and cautious LDL level is 1 person (5%). Based on Mann Whitney U test, there is relationship between nutrition status and precocious menarche occurrence (p = 0.043) and there is correlation of total cholesterol and LDLcholesterollevelswith precocious menarche (p = 0.025) and (p = 0.017). The decrease of knowledge about health of reproduction can be promoted in school by making cooperation with nutritionist to give information to parents and students of primary schools about good and healthy food.

Exercise is associated with reduction in the anxiogenic effect of mCPP on acoustic startle.

PubMed

Fox, James H; Hammack, Sayamwong E; Falls, William A

2008-08-01

Voluntary exercise has been associated with reduced anxiety across several animal models. Manipulation of central 5-HT can alter anxiety-like behaviors and administration of the 5-HT agonist metachlorophenylpiperazine (mCPP) increases anxiety in rodents and humans. To examine whether the anxiolytic effect of exercise is associated with an alteration in 5-HT systems, we examined the anxiogenic effect of mCPP in exercising and nonexercising mice. C57BL/6J mice were given 2 weeks of free access to either a functioning or nonfunctioning running wheel. Mice were then tested for acoustic startle following systemic injection of either 0, 0.1, 0.3, or 1 mg/kg of mCPP. Consistent with its anxiogenic properties, mCPP produced a dose-dependent increase in acoustic startle in nonexercising mice. However, this anxiogenic effect was blunted in exercising mice. These findings suggest that exercise may help to reduce anxiety by altering 5-HT systems, perhaps by down-regulating postsynaptic 5HT 2B/2C receptors.

Anti-Communist Vigilantes in the Philippines

DTIC Science & Technology

1988-06-03

including the founding chairman Jose Maria Sison and communist guerrilla leader Bernabe Buscayno, a.k.a. Kumander Dante. 2 Today, the CPP/NPA continues...arrest in 1976 of Jose Maria Sison, the CPP chairman. The new leadership modified the communist armed struggle by giving new impetus to urban guerilla...largest island In the Southern Philippines. The MNLF chairman Nur Misuari assisted CPP founder Jose Maria Sison in organizing the radical youth

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells

PubMed Central

Liu, Betty R.; Huang, Yue-Wern; Aronstam, Robert S.; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy. PMID:26942714

Identification of a Short Cell-Penetrating Peptide from Bovine Lactoferricin for Intracellular Delivery of DNA in Human A549 Cells.

PubMed

Liu, Betty R; Huang, Yue-Wern; Aronstam, Robert S; Lee, Han-Jung

2016-01-01

Cell-penetrating peptides (CPPs) have been shown to deliver cargos, including protein, DNA, RNA, and nanomaterials, in fully active forms into live cells. Most of the CPP sequences in use today are based on non-native proteins that may be immunogenic. Here we demonstrate that the L5a CPP (RRWQW) from bovine lactoferricin (LFcin), stably and noncovalently complexed with plasmid DNA and prepared at an optimal nitrogen/phosphate ratio of 12, is able to efficiently enter into human lung cancer A549 cells. The L5a CPP delivered a plasmid containing the enhanced green fluorescent protein (EGFP) coding sequence that was subsequently expressed in cells, as revealed by real-time PCR and fluorescent microscopy at the mRNA and protein levels, respectively. Treatment with calcium chloride increased the level of gene expression, without affecting CPP-mediated transfection efficiency. Zeta-potential analysis revealed that positively electrostatic interactions of CPP/DNA complexes correlated with CPP-mediated transport. The L5a and L5a/DNA complexes were not cytotoxic. This biomimetic LFcin L5a represents one of the shortest effective CPPs and could be a promising lead peptide with less immunogenic for DNA delivery in gene therapy.

Timing and Stages of Puberty

MedlinePlus

... and stages of puberty Timing and stages of puberty Adolescence and puberty can be so confusing! Here’s some info on what to expect and when: Puberty in girls usually starts between the ages of ...

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery.

PubMed

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future.

An efficient PEGylated liposomal nanocarrier containing cell-penetrating peptide and pH-sensitive hydrazone bond for enhancing tumor-targeted drug delivery

PubMed Central

Ding, Yuan; Sun, Dan; Wang, Gui-Ling; Yang, Hong-Ge; Xu, Hai-Feng; Chen, Jian-Hua; Xie, Ying; Wang, Zhi-Qiang

2015-01-01

Cell-penetrating peptides (CPPs) as small molecular transporters with abilities of cell penetrating, internalization, and endosomal escape have potential prospect in drug delivery systems. However, a bottleneck hampering their application is the poor specificity for cells. By utilizing the function of hydration shell of polyethylene glycol (PEG) and acid sensitivity of hydrazone bond, we constructed a kind of CPP-modified pH-sensitive PEGylated liposomes (CPPL) to improve the selectivity of these peptides for tumor targeting. In CPPL, CPP was directly attached to liposome surfaces via coupling with stearate (STR) to avoid the hindrance of PEG as a linker on the penetrating efficiency of CPP. A PEG derivative by conjugating PEG with STR via acid-degradable hydrazone bond (PEG2000-Hz-STR, PHS) was synthesized. High-performance liquid chromatography and flow cytometry demonstrated that PHS was stable at normal neutral conditions and PEG could be completely cleaved from liposome surface to expose CPP under acidic environments in tumor. An optimal CPP density on liposomes was screened to guaranty a maximum targeting efficiency on tumor cells as well as not being captured by normal cells that consequently lead to a long circulation in blood. In vitro and in vivo studies indicated, in 4 mol% CPP of lipid modified system, that CPP exerted higher efficiency on internalizing the liposomes into targeted subcellular compartments while remaining inactive and free from opsonins at a maximum extent in systemic circulation. The 4% CPPL as a drug delivery system will have great potential in the clinical application of anticancer drugs in future. PMID:26491292

Familiar companions diminish cocaine conditioning and attenuate cocaine-stimulated dopamine release in the nucleus accumbens.

PubMed

Tzeng, Wen-Yu; Cherng, Chian-Fang G; Wang, Shyi-Wu; Yu, Lung

2016-06-01

This study aimed to assess the impact of companions on the rewarding effects of cocaine. Three cage mates, serving as companions, were housed with each experimental mouse throughout cocaine-place conditioning in a cocaine-induced conditioned place preference (CPP) paradigm using conditioning doses of 10 and 20mg/kg. The presence of companions decreased the magnitude of the CPP. At 20mg/kg, cocaine stimulated dopamine (DA) release in the nucleus accumbens as evidenced by a significant decrease in total (spontaneous and electrical stimulation-provoked) DA release in accumbal superfusate samples. The presence of companions prevented this cocaine-stimulated DA release; such a reduction in cocaine-induced DA release may account for the reduction in the magnitude of the CPP in the presence of the companions. Furthermore, cocaine pretreatment (2.5mg/kg) was found to prevent the companion-produced decreases in cocaine (10mg/kg/conditioning)-induced CPP as well as the cocaine (10mg/kg)-stimulated DA release. Moreover, the presence of methamphetamine (MA) (1mg/kg)-treated companions decreased cocaine (20mg/kg/conditioning)-induced CPP and prevented the cocaine (20mg/kg)-stimulated DA release. Finally, the presence of companions decreased the magnitude of the CPP could not seem to be accounted for by cocaine-stimulated corticosterone (CORT) release. Taken together, these results indicate that familiar companions, regardless of their pharmacological status, may exert dampening effects on CPP induced by moderate to high conditioning doses of cocaine, at least in part, by preventing cocaine-stimulated DA release in the nucleus accumbens. Copyright © 2016 Elsevier B.V. All rights reserved.

Role of GABAA receptors in dorsal raphe nucleus in stress-induced reinstatement of morphine-conditioned place preference in rats.

PubMed

Li, Chen; Staub, Daniel R; Kirby, Lynn G

2013-12-01

The serotonin (5-hydroxytryptamine, 5-HT) system plays an important role in stress-related psychiatric disorders and substance abuse. Our data indicate that stress inhibits the dorsal raphe nucleus (DRN)-5-HT system via stimulation of GABA synaptic activity by the stress neurohormone corticotropin-releasing factor and, more recently, that morphine history sensitizes DRN-5-HT neurons to GABAergic inhibitory effects of stress. We tested the hypothesis that DRN GABAA receptors contribute to stress-induced reinstatement of morphine-conditioned place preference (CPP). First, we tested if activation of GABAA receptors in the DRN would reinstate morphine CPP. Second, we tested if blockade of GABAA receptors in the DRN would attenuate swim stress-induced reinstatement of morphine CPP. CPP was induced by morphine (5 mg/kg) in a 4-day conditioning phase followed by a conditioning test. Upon acquiring conditioning criteria, subjects underwent 4 days of extinction training followed by an extinction test. Upon acquiring extinction criteria, animals underwent a reinstatement test. For the first experiment, the GABAA receptor agonist muscimol (50 ng) or vehicle was injected into the DRN prior to the reinstatement test. For the second experiment, the GABAA receptor antagonist bicuculline (75 ng) or vehicle was injected into the DRN prior to a forced swim stress, and then, animals were tested for reinstatement of CPP. Intraraphe injection of muscimol reinstated morphine CPP, while intraraphe injection of bicuculline attenuated swim stress-induced reinstatement. These data provide evidence that GABAA receptor-mediated inhibition of the serotonergic DRN contributes to stress-induced reinstatement of morphine CPP.

Ritualistic chewing behavior induced by mCPP in the rat is an animal model of obsessive compulsive disorder.

PubMed

Kreiss, Deborah S; Coffman, Catherine F; Fiacco, Nicholas R; Granger, Jason C; Helton, Bernadette M; Jackson, Jennifer C; Kim, Leonid V; Mistry, Rishi S; Mizer, Tammie M; Palmer, Lolita V; Vacca, Jay A; Winkler, Stuart S; Zimmer, Benjamin A

2013-03-01

Obsessive Compulsive Disorder (OCD) is characterized by recurrent, anxiety-producing thoughts accompanied by unwanted, overwhelming urges to perform ritualistic behaviors. Pharmacological treatments for this disorder (serotonin uptake inhibitors) are problematic because there is a 6-8 week delayed onset and half of the patients do not adequately respond. The present study evaluated whether Ritualistic Chewing Behaviors (RCBs) induced by the serotonin agonist mCPP in the rat is a behavioral model for OCD. The effects upon the RCBs induced by mCPP (1 mg/kg) were evaluated following treatments with either the serotonin antagonist mianserin (3 mg/kg), the dopamine antagonist haloperidol (1 mg/kg), the GABA modulator diazepam (10 mg/kg), or the serotonin uptake inhibitors clomipramine and fluvoxamine (15 mg/kg). The response to mCPP was blocked by acute treatment with mianserin, but not with acute haloperidol or diazepam. Further experiments revealed that the effects of mCPP were blocked by chronic, but not acute, treatment with clomipramine and fluvoxamine. A time-course demonstrated that 14 days of chronic treatment were required for blockade of the mCPP-evoked response. The current study demonstrates that mCPP-evoked RCBs may be a rodent model for OCD that can be used to predict the clinical efficacy and time course of novel OCD treatment. Future investigations may be able to use the current model as a tool for bench-marking corresponding changes in other measures of neurological activity that may provide insight into the mechanisms underlying OCD. Copyright © 2013. Published by Elsevier Inc.

Oxytocin and MDMA ('Ecstasy') enhance social reward in rats.

PubMed

Ramos, Linnet; Hicks, Callum; Caminer, Alex; Goodwin, Jack; McGregor, Iain S

2015-07-01

Oxytocin (OT), vasopressin (AVP) and 3,4 methylenedioxymethamphetamine (MDMA, 'Ecstasy') all increase social interaction in rats, perhaps by enhancing the rewarding value of social encounters. Here, we used the conditioned place preference (CPP) paradigm to assess the intrinsic rewarding effects of OT, AVP and MDMA, and whether these effects are enhanced by the presence of a conspecific, or a dynamic, tactile object (a tennis ball). Adult male rats received conditioning sessions in a CPP apparatus twice a day (vehicle at 10 a.m., drug at 3 p.m.). Experiment 1 involved conditioning with OT (0.5 mg/kg, intraperitoneal (i.p.)), AVP (0.005 mg/kg, i.p.) or MDMA (5 mg/kg, i.p.). Experiments 2 and 3 involved conditioning with the same treatments but in the presence of a conspecific receiving the same treatment (social-CPP) or in the presence of a tennis ball (object-CPP), respectively. Conditioned place preference was assessed 24 h, 2 weeks and 4 weeks later. OT, AVP and MDMA did not produce a conventional CPP. However, when the conditioning environment also contained a conspecific both OT and MDMA induced a significant CPP lasting for at least 4 weeks. Rats given OT and MDMA also developed a more modest yet significant CPP for the environment where they encountered a tennis ball. These results indicate that OT and MDMA can augment the rewarding effects of social interaction, but also interaction with a dynamic and tactile non-social object. AVP does not condition social- or object-CPPs and may promote social proximity by inducing generalized anxiety and defensive aggregation.

Acoustic analyses of thyroidectomy-related changes in vowel phonation.

PubMed

Solomon, Nancy Pearl; Awan, Shaheen N; Helou, Leah B; Stojadinovic, Alexander

2012-11-01

Changes in vocal function that can occur after thyroidectomy were tracked with acoustic analyses of sustained vowel productions. The purpose was to determine which time-based or spectral/cepstral-based measures of two vowels were able to detect voice changes over time in patients undergoing thyroidectomy. Prospective, longitudinal, and observational clinical trial. Voice samples of sustained /ɑ/ and /i/ recorded from 70 adults before and approximately 2 weeks, 3 months, and 6 months after thyroid surgery were analyzed for jitter, shimmer, harmonic-to-noise ratio (HNR), cepstral peak prominence (CPP), low-to-high ratio of spectral energy (L/H ratio), and the standard deviations of CPP and L/H ratio. Three trained listeners rated vowel and sentence productions for the four data collection sessions for each participant. For analysis purposes, participants were categorized post hoc according to voice outcome (VO) at their first postthyroidectomy assessment session. Shimmer, HNR, and CPP differed significantly across sessions; follow-up analyses revealed the strongest effect for CPP. CPP for /ɑ/ and /i/ differed significantly between groups of participants with normal versus negative (adverse) VO and between the pre- and 2-week postthyroidectomy sessions for the negative VO group. HNR, CPP, and L/H ratio differed across vowels, but both /ɑ/ and /i/ were similarly effective in tracking voice changes over time and differentiating VO groups. This study indicated that shimmer, HNR, and CPP determined from vowel productions can be used to track changes in voice over time as patients undergo and subsequently recover from thyroid surgery, with CPP being the strongest variable for this purpose. Evidence did not clearly reveal whether acoustic voice evaluations should include both /ɑ/ and /i/ vowels, but they should specify which vowel is used to allow for comparisons across studies and multiple clinical assessments. Copyright © 2012 The Voice Foundation. All rights reserved.

Role of the Dopaminergic System in the Acquisition, Expression and Reinstatement of MDMA-Induced Conditioned Place Preference in Adolescent Mice

PubMed Central

Vidal-Infer, Antonio; Roger-Sánchez, Concepción; Daza-Losada, Manuel; Aguilar, María A.; Miñarro, José; Rodríguez-Arias, Marta

2012-01-01

Background The rewarding effects of 3,4-methylenedioxy-metamphetamine (MDMA) have been demonstrated in conditioned place preference (CPP) procedures, but the involvement of the dopaminergic system in MDMA-induced CPP and reinstatement is poorly understood. Methodology/Principal Findings In this study, the effects of the DA D1 antagonist SCH 23390 (0.125 and 0.250 mg/kg), the DA D2 antagonist Haloperidol (0.1 and 0.2 mg/kg), the D2 antagonist Raclopride (0.3 and 0.6 mg/kg) and the dopamine release inhibitor CGS 10746B (3 and 10 mg/kg) on the acquisition, expression and reinstatement of a CPP induced by 10 mg/kg of MDMA were evaluated in adolescent mice. As expected, MDMA significantly increased the time spent in the drug-paired compartment during the post-conditioning (Post-C) test, and a priming dose of 5 mg/kg reinstated the extinguished preference. The higher doses of Haloperidol, Raclopride and CGS 10746B and both doses of SCH 23390 blocked acquisition of the MDMA-induced CPP. However, only Haloperidol blocked expression of the CPP. Reinstatement of the extinguished preference was not affected by any of the drugs studied. Analysis of brain monoamines revealed that the blockade of CPP acquisition was accompanied by an increase in DA concentration in the striatum, with a concomitant decrease in DOPAC and HVA levels. Administration of haloperidol during the Post-C test produced increases in striatal serotonin, DOPAC and HVA concentrations. In mice treated with the higher doses of haloperidol and CGS an increase in SERT concentration in the striatum was detected during acquisition of the CPP, but no changes in DAT were observed. Conclusions/Significance These results demonstrate that, in adolescent mice, the dopaminergic system is involved in the acquisition and expression of MDMA-induced CPP, but not in its reinstatement. PMID:22916213

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice

PubMed Central

Golden, Sam A.; Aleyasin, Hossein; Heins, Robert; Flanigan, Meghan; Heshmati, Mitra; Takahashi, Aki; Russo, Scott J.; Shaham, Yavin

2016-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3–4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1xC57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening didn’t develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1xD1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. PMID:27457669

Food deprivation facilitates reinstatement of morphine-induced conditioned place preference: Role of intra-accumbal dopamine D2-like receptors in associating reinstatement of morphine CPP with stress.

PubMed

Sadeghzadeh, Fatemeh; Babapour, Vahab; Haghparast, Abbas

2017-04-01

The high rate of relapse to drug use is one of the main problems in the treatment of addiction. Stress plays the essential role in drug abuse and relapse; nevertheless, little is known about the mechanisms underlying stress and relapse. Accordingly, the effects of intra-accumbal administration of Sulpiride, as a dopamine D2-like receptor antagonist, on an ineffective morphine dose + food deprivation(FD)- and morphine priming-induced reinstatement of conditioned place preference (CPP). About 104 adult male albino Wistar rats weighing 200-280 g were bilaterally implanted by cannula into the nucleus accumbens (NAc). Subcutaneous (sc) injection of morphine (5 mg kg -1 ) was used daily during a 3-day conditioning phase. After a 24-hr "off" period following achievement of extinction criterion, rats were tested for FD- and priming-induced reinstatement of morphine CPP by an ineffective (0.5 mg kg -1 , sc) and priming (1 mg kg -1 , sc) dose of morphine, respectively. In the next experiments, animals received different doses of intra-accumbal Sulpiride (0.25, 1, and 4 µg/0.5 µL saline) bilaterally and were subsequently tested for morphine reinstatement. Our findings indicated that the 24-hr FD facilitated reinstatement of morphine CPP. Furthermore, the D2-like receptor antagonist attenuated the ineffective morphine dose+ FD- and priming-induced reinstatement of morphine CPP dose-dependently. Also, contribution of D2-like receptors in mediation of the ineffective morphine dose+ FD-induced reinstatement of CPP was greater than morphine priming-induced reinstatement of CPP. The role of dopaminergic system in morphine reinstatement through a neural pathway in the NAc provides the evidence that D2-like receptor antagonist can be useful therapeutic targets for reinstatement of morphine CPP. © 2016 Wiley Periodicals, Inc.

Persistent conditioned place preference to aggression experience in adult male sexually-experienced CD-1 mice.

PubMed

Golden, S A; Aleyasin, H; Heins, R; Flanigan, M; Heshmati, M; Takahashi, A; Russo, S J; Shaham, Y

2017-01-01

We recently developed a conditioned place preference (CPP) procedure, commonly used to study rewarding drug effects, to demonstrate that dominant sexually-experienced CD-1 male mice form CPP to contexts previously associated with defeating subordinate male C57BL/6J mice. Here we further characterized conditioned and unconditioned aggression behavior in CD-1 mice. In Exp. 1 we used CD-1 mice that displayed a variable spectrum of unconditioned aggressive behavior toward younger subordinate C57BL/6J intruder mice. We then trained the CD-1 mice in the CPP procedure where one context was intruder-paired, while a different context was not. We then tested for aggression CPP 1 day after training. In Exp. 2, we tested CD-1 mice for aggression CPP 1 day and 18 days after training. In Exp. 3-4, we trained the CD-1 mice to lever-press for palatable food and tested them for footshock punishment-induced suppression of food-reinforced responding. In Exp. 5, we characterized unconditioned aggression in hybrid CD-1 × C57BL/6J D1-Cre or D2-Cre F1 generation crosses. Persistent aggression CPP was observed in CD-1 mice that either immediately attacked C57BL/6J mice during all screening sessions or mice that gradually developed aggressive behavior during the screening phase. In contrast, CD-1 mice that did not attack the C57BL/6J mice during screening did not develop CPP to contexts previously paired with C57BL/6J mice. The aggressive phenotype did not predict resistance to punishment-induced suppression of food-reinforced responding. CD-1 × D1-Cre or D2-Cre F1 transgenic mice showed strong unconditioned aggression. Our study demonstrates that aggression experience causes persistent CPP and introduces transgenic mice for circuit studies of aggression. © 2016 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.

High yield Cu-Co CPP GMR multilayer sensors

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

Spallas, J.; Mao, M.; Law, B.

1997-01-15

We have fabricated and tested GMR magnetic flux sensors that operate in the CPP mode. This work is a continuation of the ultra-high density magnetic sensor research introduced at INTERMAG 96. We have made two significant modifications to the process sequence. First, contact to the sensor is made through a metal conduit deposited in situ with the multilayers. This deposition replaces electroplating. This configuration ensures a good electrical interface between the top of multilayer stack and the top contact, and a continuous, conductive current path to the sensor. The consequences of this modification are an increase in yield of operationalmore » devices to {ge}90% per wafer and a significant reduction of the device resistance to {le}560 milliohms and of the uniformity of the device resistance to {le}3%. Second, the as-deposited multilayer structure has been changed from [Cu 30 {angstrom}/Co 20 {angstrom}]{sub 18} (third peak) to [Cu 20.5 {angstrom}/Co 12 {angstrom}]{sub 30} (second peak) to increase the CPP and CIP responses. The sheet film second peak CIP GMR response is 18% and the sensitivity is 0.08 %/Oe. The sheet film third peak CIP GMR response is 8% and the sensitivity is 0. 05 %/Oe. The second peak CPP GMR response averaged over twenty devices on a four inch silicon substrate is 28% {+-} 6%. The response decreases radially from the substrate center. The average response at the center of the substrate is 33% {+-} 4%. The average second peak CPP sensitivity is 0.09 %/Oe {+-} 0.02 %/Oe. The best second peak CPP response from a single device is 39%. The sensitivity of that device is 0.13 %/Oe. The third peak CPP GMR response is approximately 14 %. The third peak CPP response sensitivity is 0.07 %/Oe. 6 refs., 3 figs.« less

Methylation profiling of choroid plexus tumors reveals 3 clinically distinct subgroups.

PubMed

Thomas, Christian; Sill, Martin; Ruland, Vincent; Witten, Anika; Hartung, Stefan; Kordes, Uwe; Jeibmann, Astrid; Beschorner, Rudi; Keyvani, Kathy; Bergmann, Markus; Mittelbronn, Michel; Pietsch, Torsten; Felsberg, Jörg; Monoranu, Camelia M; Varlet, Pascale; Hauser, Peter; Olar, Adriana; Grundy, Richard G; Wolff, Johannes E; Korshunov, Andrey; Jones, David T; Bewerunge-Hudler, Melanie; Hovestadt, Volker; von Deimling, Andreas; Pfister, Stefan M; Paulus, Werner; Capper, David; Hasselblatt, Martin

2016-06-01

Choroid plexus tumors are intraventricular neoplasms derived from the choroid plexus epithelium. A better knowledge of molecular factors involved in choroid plexus tumor biology may aid in identifying patients at risk for recurrence. Methylation profiles were examined in 29 choroid plexus papillomas (CPPs, WHO grade I), 32 atypical choroid plexus papillomas (aCPPs, WHO grade II), and 31 choroid plexus carcinomas (CPCs, WHO grade III) by Illumina Infinium HumanMethylation450 Bead Chip Array. Unsupervised hierarchical clustering identified 3 subgroups: methylation cluster 1 (pediatric CPP and aCPP of mainly supratentorial location), methylation cluster 2 (adult CPP and aCPP of mainly infratentorial location), and methylation cluster 3 (pediatric CPP, aCPP, and CPC of supratentorial location). In methylation cluster 3, progression-free survival (PFS) accounted for a mean of 72 months (CI, 55-89 mo), whereas only 1 of 42 tumors of methylation clusters 1 and 2 progressed (P< .001). On stratification of outcome data according to WHO grade, all CPCs clustered within cluster 3 and were associated with shorter overall survival (mean, 105 mo [CI, 81-128 mo]) and PFS (mean, 55 mo [CI, 36-73 mo]). The aCPP of methylation cluster 3 also progressed frequently (mean, 69 mo [CI, 44-93 mo]), whereas no tumor progression was observed in aCPP of methylation clusters 1 and 2 (P< .05). Only 1 of 29 CPPs recurred. Methylation profiling of choroid plexus tumors reveals 3 distinct subgroups (ie, pediatric low-risk choroid plexus tumors [cluster 1], adult low-risk choroid plexus tumors [cluster 2], and pediatric high-risk choroid plexus tumors [cluster 3]) and may provide useful prognostic information in addition to histopathology. Published by Oxford University Press on behalf of the Society for Neuro-Oncology 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

Casein phosphopeptides and CaCl2 increase penicillin production and cause an increment in microbody/peroxisome proteins in Penicillium chrysogenum.

PubMed

Domínguez-Santos, Rebeca; Kosalková, Katarina; García-Estrada, Carlos; Barreiro, Carlos; Ibáñez, Ana; Morales, Alejandro; Martín, Juan-Francisco

2017-03-06

Transport of penicillin intermediates and penicillin secretion are still poorly characterized in Penicillium chrysogenum (re-identified as Penicillium rubens). Calcium (Ca 2+ ) plays an important role in the metabolism of filamentous fungi, and casein phosphopeptides (CPP) are involved in Ca 2+ internalization. In this study we observe that the effect of CaCl 2 and CPP is additive and promotes an increase in penicillin production of up to 10-12 fold. Combination of CaCl 2 and CPP greatly promotes expression of the three penicillin biosynthetic genes. Comparative proteomic analysis by 2D-DIGE, identified 39 proteins differentially represented in P. chrysogenum Wisconsin 54-1255 after CPP/CaCl 2 addition. The most interesting group of overrepresented proteins were a peroxisomal catalase, three proteins of the methylcitrate cycle, two aminotransferases and cystationine β-synthase, which are directly or indirectly related to the formation of penicillin amino acid precursors. Importantly, two of the enzymes of the penicillin pathway (isopenicillin N synthase and isopenicillin N acyltransferase) are clearly induced after CPP/CaCl 2 addition. Most of these overrepresented proteins are either authentic peroxisomal proteins or microbody-associated proteins. This evidence suggests that addition of CPP/CaCl 2 promotes the formation of penicillin precursors and the penicillin biosynthetic enzymes in peroxisomes and vesicles, which may be involved in transport and secretion of penicillin. Penicillin biosynthesis in Penicillium chrysogenum is one of the best characterized secondary metabolism processes. However, the mechanism by which penicillin is secreted still remains to be elucidated. Taking into account the role played by Ca 2+ and CPP in the secretory pathway and considering the positive effect that Ca 2+ exerts on penicillin production, the analysis of global protein changes produced after CPP/CaCl 2 addition is very helpful to decipher the processes related to the biosynthesis and secretion of penicillin. Copyright © 2017 Elsevier B.V. All rights reserved.

Caries-Preventive Effect of NaF, NaF plus TCP, NaF plus CPP-ACP, and SDF Varnishes on Sound Dentin and Artificial Dentin Caries in vitro.

PubMed

Wierichs, Richard J; Stausberg, Sabrina; Lausch, Julian; Meyer-Lueckel, Hendrik; Esteves-Oliveira, Marcella

2018-01-01

The aim of this study was to compare the caries-preventive effect of different fluoride varnishes on sound dentin as well as on artificial dentin caries-like lesions. Bovine dentin specimens (n = 220) with one sound surface (ST) and one artificial caries lesion (DT) were prepared and randomly allocated to 11 groups. The interventions before pH cycling were as follows: application of a varnish containing NaF (22,600 ppm F-; Duraphat [NaF0/NaF1]), NaF plus tricalcium phosphate (22,600 ppm F-; Clinpro White Varnish Mint [TCP0/TCP1]), NaF plus casein phosphopeptide-stabilized amorphous calcium phosphate complexes (CPP-ACP; 22,600 ppm F-; MI Varnish [CPP0/CPP1]), or silver diamine fluoride (SDF; 35,400 ppm F-; Cariestop 30% [SDF0/SDF1]) and no intervention (NNB/N0/N1). During pH cycling (14 days, 6 × 120 min demineralization/day) half of the specimens in each group were brushed (10 s; 2 times/day) with either fluoride-free ("0"; e.g., TCP0) or 1,100 ppm F- ("1"; e.g., TCP1) dentifrice slurry. In another subgroup, the specimens were pH cycled but not brushed (NNB). Differences in integrated mineral loss (ΔΔZ), lesion depth (ΔLD), and colorimetric values (ΔΔE) were calculated between the values after initial demineralization and those after pH cycling, using transversal microradiography and photographic images. After pH cycling, no discoloration could be observed. Furthermore, NNB, N0, and N1 showed significantly increased ΔZDT/LDDT and ΔZST/LDST values, indicating further demineralization. In contrast, CPP0, CPP1, SDF0, and SDF1 showed significantly decreased ΔZDT/LDDT values, indicating remineralization (p ≤ 0.004; paired t test). CPP0, CPP1, SDF0, and SDF1 showed significantly higher changes in ΔΔZDT/ΔLDDT and ΔΔZST/ΔLDST than NNB, N0, and N1 (p < 0.001; Bonferroni post hoc test). In conclusion, under the conditions chosen, all fluoride varnishes prevented further demineralization. However, only NaF plus CPP-ACP and SDF could remineralize artificial dentin caries-like lesions under net-demineralizing conditions, thereby indicating that NaF plus CPP-ACP and SDF may be helpful to high-caries-risk patients. © 2018 S. Karger AG, Basel.

South Africa and the 21st Century Power Partnership: Paving the Way to a Clean, Reliable, and Resilient Power System

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

2017-05-09

The 21st Century Power Partnership (21CPP) serves as an open, collaborative platform for sharing policy and regulatory best practices in the service of power system transformation. Established in 2012, the 21CPP South Africa Programme is a global initiative that connects South African stakeholders with an international community of expertise. This fact sheet details the 21CPP South Africa Programme.

Chronic Pelvic Pain: Assessment, Evaluation, and Objectivation

PubMed Central

Pota, Vincenzo; Sansone, Pasquale; Aurilio, Caterina; Pace, Maria Caterina

2017-01-01

Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. PMID:29359045

Pre-conditioned place preference treatment of chloral hydrate interrupts the rewarding effect of morphine.

PubMed

Sun, YongMei; Zong, Wei; Zhou, MuRu; Ma, YuanYe; Wang, JianHong

2015-08-01

The medical use of morphine as a pain killer is hindered by its side effects including dependence and further addiction. As the prototypical μ receptor agonist, morphine's rewarding effect can be measured by conditioned place preference (CPP) paradigms in animals. Chloral hydrate is a clinical sedative. Using a morphine CPP paradigm that mainly contains somatosensory cues, we found that pre-CPP treatment in rats using chloral hydrate for 6 consecutive days could disrupt the establishment of CPP in a U shape. Chloral hydrate had no effect on the body weight of rats. Our results indicate that prior treatment with chloral hydrate can interrupt the rewarding effect of morphine. Copyright © 2015 Elsevier Inc. All rights reserved.

Accelerated behavioural development changes fine-scale search behaviour and spatial memory in honey bees (Apis mellifera L.).

PubMed

Ushitani, Tomokazu; Perry, Clint J; Cheng, Ken; Barron, Andrew B

2016-02-01

Normally, worker honey bees (Apis mellifera) begin foraging when more than 2 weeks old as adults, but if individual bees or the colony is stressed, bees often begin foraging precociously. Here, we examined whether bees that accelerated their behavioural development to begin foraging precociously differed from normal-aged foragers in cognitive performance. We used a social manipulation to generate precocious foragers from small experimental colonies and tested their performance in a free-flight visual reversal learning task, and a test of spatial memory. To assess spatial memory, bees were trained to learn the location of a small sucrose feeder within an array of three landmarks. In tests, the feeder and one landmark were removed and the search behaviour of the bees was recorded. Performance of precocious and normal-aged foragers did not differ in a visual reversal learning task, but the two groups showed a clear difference in spatial memory. Flight behaviour suggested normal-aged foragers were better able to infer the position of the removed landmark and feeder relative to the remaining landmarks than precocious foragers. Previous studies have documented the cognitive decline of old foragers, but this is the first suggestion of a cognitive deficit in young foragers. These data imply that worker honey bees continue their cognitive development during the adult stage. These findings may also help to explain why precocious foragers perform quite poorly as foragers and have a higher than normal loss rate. © 2016. Published by The Company of Biologists Ltd.

Effect of Casein Phosphopeptide-amorphous Calcium Phosphate Treatment on Microtensile Bond Strength to Carious Affected Dentin Using Two Adhesive Strategies

PubMed Central

Bahari, Mahmoud; Savadi Oskoee, Siavash; Kimyai, Soodabeh; Pouralibaba, Firoz; Farhadi, Farrokh; Norouzi, Marouf

2014-01-01

Background and aims. The aim was to evaluate the effect of casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) on microtensile bond strength (μTBS) to carious affected dentin (CAD) using etch-and-rinse and self-etch adhesive systems. Materials and methods. The occlusal surface of 32 human molars with moderate occlusal caries was removed. Infected dentin was removed until reaching CAD and the teeth were randomly divided into two groups based on the Single Bond (SB) and Clearfil SE Bond (CSE) adhesive systems. Before composite resin bonding, each group was subdivided into three subgroups of ND, CAD and CPP-ACP-treated CAD (CAD-CPP) based on the dentin substrate. After dissecting samples to l-mm-thick cross-sections (each subgroup: n = 13), μTBS was measured at a strain rate of 0.5 mm/min. Data was analyzed using two-way ANOVA, independent samples t-test and post-hoc Tukey tests (α=0.05). Results. Bond strength of both adhesive systems to ND was significantly higher than that to CAD (P <0.001) and CAD/CPP (P < 0.001). There were no significant differences between the μTBS of SB to CAD and CAD-CPP (P > 0.05).μTBS of CSE to CAD-CPP was higher than that to CAD; however, the difference was not significant (P > 0.05). Significant differences were found between SB and CSE systems only with CAD substrate (P < 0.001). Conclusion. Regardless of the adhesive system used, surface treatment of CAD with CPP-ACP did not have a significant effect on bond strength. However, bond strength to CAD was higher with SB rather than with CSE. PMID:25346832

Evaluation of the Contralateral Inguinal Ring in Clinically Unilateral Inguinal Hernia: A Systematic Review and Meta-analysis

PubMed Central

Kokorowski, Paul J; Wang, Hsin-Hsiao Scott; Routh, Jonathan C; Hubert, Katherine C; Nelson, Caleb P

2013-01-01

Purpose The management of the contralateral inguinal canal in children with clinical unilateral inguinal hernia is controversial. Our objective was to systematically review the literature regarding management of the contralateral inguinal canal. Methods We searched MEDLINE, EMBASE, and Cochrane databases (1940–2011) using ‘hernia’ and ‘inguinal’ and either ‘pediatric,’ ‘infant,’ or ‘child,’ to identify studies of pediatric (age≤21 yrs) patients with inguinal hernia. Among clinical unilateral hernia patients, we assessed the number of cases with contralateral patent processus (CPP) and incidence of subsequent clinical metachronous contralateral hernia (MCH). We evaluated three strategies for contralateral management: expectant management, laparoscopic evaluation or pre-operative ultrasound. Pooled estimates of MCH or CPP were generated with random effects by study when heterogeneity was found (I2>50%, or Cochrane’s Q p≥0.10). Results We identified 2,477 non-duplicated studies, 129 of which met our inclusion criteria and had sufficient information for quantitative analysis. The pooled incidence of MCH after open unilateral repair was 7.3% (95% CI 6.5%–8.1%). Laparoscopic examination identified CPP in 30% (95% CI 26%–34%). Lower age was associated with higher incidence of CPP (p<0.01). The incidence of MCH after a negative laparoscopic evaluation was 0.9% (95% CI 0.5%–1.3%). Significant heterogeneity was found in studies and pooled estimates should be interpreted with caution. Conclusions The literature suggests that laparoscopically identified CPP is a poor indicator of future contralateral hernia. Almost a third of patients will have a CPP, while less than one in 10 will develop MCH when managed expectantly. Performing contralateral hernia repair in patients with CPP results in overtreatment in roughly 2 out of 3 patients. PMID:23963735

On the behavioural specificity of hypophagia induced in male rats by mCPP, naltrexone, and their combination.

PubMed

Wright, F L; Rodgers, R J

2014-02-01

Serotonergic (5-hydroxytryptamine, 5-HT) and opioidergic mechanisms are intimately involved in appetite regulation. In view of recent evidence of positive anorectic interactions between opioid and various non-opioid substrates, our aim was to assess the behavioural specificity of anorectic responses to the opioid receptor antagonist naltrexone, the 5-HT2C/1B receptor agonist mCPP and their combination. Behavioural profiling techniques, including the behavioural satiety sequence (BSS), were used to examine acute drug effects in non-deprived male rats tested with palatable mash. Experiment 1 characterised the dose-response profile of mCPP (0.1-3.0 mg/kg), while experiment 2 assessed the effects of combined treatment with a sub-anorectic dose of mCPP (0.1 mg/kg) and one of two low doses of naltrexone (0.1 and 1.0 mg/kg). Experiment 1 confirmed the dose-dependent anorectic efficacy of mCPP, with robust effects on intake and feeding-related measures observed at 3.0 mg/kg. However, that dose was also associated with other behavioural alterations including increased grooming, reductions in locomotion and sniffing, and disruption of the BSS. In experiment 2, naltrexone dose-dependently reduced food intake and time spent feeding, effects accompanied by a behaviourally selective acceleration in the BSS. However, the addition of 0.1 mg/kg mCPP did not significantly alter the behavioural changes observed in response to either dose of naltrexone given alone. In contrast to recently reported positive anorectic interactions involving low-dose combinations of opioid receptor antagonists or mCPP with cannabinoid CB1 receptor antagonists, present results would not appear to provide any support for potentially clinically relevant anorectic interactions between opioid and 5-HT2C/1B receptor mechanisms.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats.

PubMed

Voigt, Robin M; Riddle, Jennifer L; Napier, T Celeste

2014-05-01

Fendiline is a GABAB receptor-positive allosteric modulator and L-type Ca²⁺ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans Following meth conditioning (1 mg/kg), fendiline (5 mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p < 0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p < 0.05) or those that received two injections that corresponded to the last 2 days of the 10-day treatment (p < 0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans.

Effect of CPP-ACP on the remineralization of acid-eroded human tooth enamel: nanomechanical properties and microtribological behaviour study

NASA Astrophysics Data System (ADS)

Zheng, L.; Zheng, J.; Zhang, Y. F.; Qian, L. M.; Zhou, Z. R.

2013-10-01

Casein phosphopeptide-stabilized amorphous calcium phosphate (CPP-ACP) has been used to enhance tooth remineralization in the dental clinic. But the contribution of CPP-ACP to the remineralization of acid-eroded human tooth enamel is of widespread controversy. To confirm the application potential of CPP-ACP in the remineralization repair of tooth erosion caused by acid-attack, the effect of remineralization in vitro in 2% w/v CPP-ACP solution on the acid-eroded human tooth enamel was investigated in this study. The repair of surface morphology and the improvement of nanomechanical and microtribological properties were characterized with laser confocal scanning microscope, scanning electron microscope, nanoindentation tester and nanoscratch tester. Results showed that a layer of uneven mineral deposits, which were mainly amorphous calcium phosphate (ACP) in all probability, was observed on the acid-eroded enamel surface after remineralization. Compared with the acid-eroded enamel surface, the nanoindentation hardness and Young's modulus of the remineralized enamel surface obviously increased. Both the friction coefficient and wear volume of the acid-eroded enamel surface decreased after remineralization. However, both the nanomechanical and the anti-wear properties of the remineralized enamel surface were still inferior to those of original enamel surface. In summary, tooth damage caused by acid erosion could be repaired by remineralization in CPP-ACP solution, but the repair effect, especially on the nanomechanical and anti-wear properties of the acid-eroded enamel, was limited. These results would contribute to a further exploration of the remineralization potential of CPP-ACP and a better understanding of the remineralization repair mechanism for acid-eroded human tooth enamel.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel.

PubMed

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond.

In vitro evaluation of casein phosphopeptide-amorphous calcium phosphate effect on the shear bond strength of dental adhesives to enamel

PubMed Central

Shadman, Niloofar; Ebrahimi, Shahram Farzin; Shoul, Maryam Azizi; Sattari, Hasti

2015-01-01

Background: Casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) is applied for remineralization of early caries lesions or tooth sensitivity conditions and may affect subsequent resin bonding. This in vitro study investigated the effect of CPP-ACP on the shear bond strength of dental adhesives to enamel. Materials and Methods: Sixty extracted human molar teeth were selected and randomly divided into three groups and six subgroups. Buccal or lingual surfaces of teeth were prepared to create a flat enamel surface. Adhesives used were Tetric N-Bond, AdheSE and AdheSE One F. In three subgroups, before applying adhesives, enamel surfaces were treated with Tooth Mousse CPP-ACP for one hour, rinsed and stored in 37°C temperature with 100% humidity. This procedure was repeated for 5 days and then adhesives were applied and Tetric N-Ceram composite was adhered to the enamel. This procedure was also fulfilled for the other three subgroups without CPP-ACP treatment. After 24 hour water storage, samples were tested for shear bond strength test in a universal testing machine. Failure modes were determined by stereomicroscope. Data were analyzed by t-test and one-way analysis of variance with P < 0.05 as the level of significance. Results: In comparison between applied and non-applied CPP-ACP subgroups, there was no significant decrease in the shear bond strength to enamel only in Tetric N-Bond (P > 0.05). In non-applied CPP-ACP subgroups, there were statistically significant differences among all subgroups. Tetric N-Bond had the highest and AdheSE One F had the lowest shear bond strength. Conclusion: CPP-ACP application reduces the shear bond strength of AdheSE and AdheSE One F to enamel but not Tetric N-Bond. PMID:25878683

Social housing conditions influence morphine dependence and the extinction of morphine place preference in adolescent mice.

PubMed

Bates, M L Shawn; Emery, Michael A; Wellman, Paul J; Eitan, Shoshana

2014-09-01

Adolescent opioid abuse is on the rise, and current treatments are not effective in reducing rates of relapse. Our previous studies demonstrated that social housing conditions alter the acquisition rate of morphine conditioned place preference (CPP) in adolescent mice. Specifically, the acquisition rate of morphine CPP is slower in morphine-treated animals housed with drug-naïve animals. Thus, here we tested the effect of social housing conditions on the development of morphine dependence and the extinction rate of an acquired morphine CPP. Adolescent male mice were group-housed in one of two housing conditions. They were injected for 6 days (PND 28-33) with 20 mg/kg morphine. Morphine only mice are animals where all four mice in the cage received morphine. Morphine cage-mate mice are morphine-injected animals housed with drug-naïve animals. Mice were individually tested for spontaneous withdrawal signs by quantifying jumping behavior 4, 8, 24, and 48 h after the final morphine injection. Then, mice were conditioned to acquire morphine CPP and were tested for the rate of extinction. Morphine cage-mates express less jumping behavior during morphine withdrawal as compared to morphine only mice. As expected, morphine cage-mate animals acquired morphine CPP more slowly than the morphine only animals. Additionally, morphine cage-mates extinguished morphine CPP more readily than morphine only mice. Social housing conditions modulate morphine dependence and the extinction rate of morphine CPP. Extinction testing is relevant to human addiction because rehabilitations like extinction therapy may be used to aid human addicts in maintaining abstinence from drug use. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

Stress and opioids: role of opioids in modulating stress-related behavior and effect of stress on morphine conditioned place preference.

PubMed

Bali, Anjana; Randhawa, Puneet Kaur; Jaggi, Amteshwar Singh

2015-04-01

Research studies have defined the important role of endogenous opioids in modulating stress-associated behavior. The release of β-endorphins in the amygdala in response to stress helps to cope with a stressor by inhibiting the over-activation of HPA axis. Administration of mu opioid agonists reduces the risk of developing post-traumatic stress disorder (PTSD) following a traumatic event by inhibiting fear-related memory consolidation. Similarly, the release of endogenous enkephalin and nociceptin in the basolateral amygdala and the nucleus accumbens tends to produce the anti-stress effects. An increase in dynorphin levels during prolonged exposure to stress may produce learned helplessness, dysphoria and depression. Stress also influences morphine-induced conditioned place preference (CPP) depending upon the intensity and duration of the stressor. Acute stress inhibits morphine CPP, while chronic stress potentiates CPP. The development of dysphoria due to increased dynorphin levels may contribute to chronic stress-induced potentiation of morphine CPP. The activation of ERK/cyclic AMP responsive element-binding (CREB) signaling in the mesocorticolimbic area, glucocorticoid receptors in the basolateral amygdala, and norepinephrine and galanin system in the nucleus accumbens may decrease the acute stress-induced inhibition of morphine CPP. The increase in dopamine levels in the nucleus accumbens and augmentation of GABAergic transmission in the median prefrontal cortex may contribute in potentiating morphine CPP. Stress exposure reinstates the extinct morphine CPP by activating the orexin receptors in the nucleus accumbens, decreasing the oxytocin levels in the lateral septum and amygdala, and altering the GABAergic transmission (activation of GABAA and inactivation of GABAB receptors). The present review describes these varied interactions between opioids and stress along with the possible mechanism. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effect of fendiline on the maintenance and expression of methamphetamine-induced conditioned place preference in Sprague-Dawley rats

PubMed Central

Voigt, Robin M.; Riddle, Jennifer L.; Napier, T. Celeste

2014-01-01

Rationale Fendiline is a GABAB receptor positive allosteric modulator and L-type Ca2+ channel blocker that is safe for human use. Based on these pharmacological properties, fendiline may be useful to disrupt associative memories that can drive relapse to drug use in drug-addicted individuals. Objective The current study evaluated the potential of fendiline to inhibit the maintenance and expression of learned associations between methamphetamine (meth) and an environmental context using conditioned place preference (CPP) in rats, to model for the associative learning that occurs during drug abuse by humans. Methods Following meth conditioning (1mg/kg), fendiline (5mg/kg) was administered at various post-conditioning times to ascertain if there was a temporal window during which fendiline would be effective. Results Two once-daily injections of fendiline did not influence the maintenance of CPP regardless of the post-conditioning treatment time while 10 once-daily fendiline treatments inhibited CPP maintenance (p<0.05). Fendiline administered immediately prior to the CPP test inhibited expression of meth-induced CPP in rats with a fendiline treatment history of 10 once-daily injections (p<0.05) or those that received two injections that corresponded to the last two days of the 10 day treatment (p<0.05). Fendiline did not produce preference or aversion on its own, nor did it alter motivated motor behavior. Conclusion Maintenance and expression of meth CPP is mitigated by repeated fendiline treatments when administered during the days that precede CPP testing. Reduction in the significance of meth-associated cues can reduce relapse; therefore, fendiline may be of value for addiction therapy in abstinent, meth-addicted humans. PMID:24264565

Dopamine D1/D5 receptors in the dorsal hippocampus are required for the acquisition and expression of a single trial cocaine-associated memory.

PubMed

Kramar, Cecilia P; Barbano, M Flavia; Medina, Jorge H

2014-12-01

The role of the hippocampus in memory supporting associative learning between contexts and unconditioned stimuli is well documented. Hippocampal dopamine neurotransmission modulates synaptic plasticity and memory processing of fear-motivated and spatial learning tasks. Much less is known about the involvement of the hippocampus and its D1/D5 dopamine receptors in the acquisition, consolidation and expression of memories for drug-associated experiences, more particularly, in the processing of single pairing cocaine conditioned place preference (CPP) training. To determine the temporal dynamics of cocaine CPP memory formation, we trained rats in a one-pairing CPP paradigm and tested them at different time intervals after conditioning. The cocaine-associated memory lasted 24 h but not 72 h. Then, we bilaterally infused the dorsal hippocampus with the GABA A receptor agonist muscimol or the D1/D5 dopamine receptor antagonist SCH 23390 at different stages to evaluate the mechanisms involved in the acquisition, consolidation or expression of cocaine CPP memory. Blockade of D1/D5 dopamine receptors at the moment of training impaired the acquisition of cocaine CPP memories, without having any effect when administered immediately or 12 h after training. The expression of cocaine CPP memory was also affected by the administration of SCH 23390 at the moment of the test. Conversely, muscimol impaired the consolidation of cocaine CPP memory only when administered 12 h post conditioning. These findings suggests that dopaminergic inputs to the dorsal hippocampus are required for the acquisition and expression of one trial cocaine-associated memory while neural activity of this structure is required for the late consolidation of these types of memories. Copyright © 2014 Elsevier Inc. All rights reserved.

Monitoring of Intracranial Pressure in Meningitis.

PubMed

Depreitere, Bart; Bruyninckx, Dominike; Güiza, Fabian

2016-01-01

The literature on intracranial pressure (ICP) monitoring in meningitis is limited to case reports and a handful of descriptive series. The aim of this study is to investigate relationships among ICP, cerebral perfusion pressure (CPP), and outcome in meningitis and to identify whether ICP affected clinical decisions. Between 1999 and 2011, a total of 17 patients with meningitis underwent ICP monitoring at the University Hospitals Leuven. Charts were reviewed for clinical history, ICP/CPP data, imaging findings, and Glasgow Outcome Scale score. Univariate correlations were computed for outcome and ICP/CPP variables, computed tomography characteristics, and Corticosteroid Randomization After Significant Head Injury outcome model variables. Treatment decisions were assessed regarding whether or not they were based on ICP. At drain placement, Glasgow Coma Scale scores showed a median of 8 (range 3-12). Six of 17 patients had either one or two nonreactive pupils. Significant correlations with outcome were found for the highest documented ICP value (r = -0.70), the number of episodes when CPP <50 mmHg (r =-0.50), the lowest documented CPP value (r = 0.61), and pupil reactivity (r = 0.57). Treatment was influenced by ICP in all patients. The results support the notion that in meningitis high ICP and low CPP represent secondary insults. The poor condition of the patients illustrates that the level of suspicion for increased ICP in meningitis may not be high enough.

Dynamic Cerebrovascular and Intracranial Pressure Reactivity Assessment of Impaired Cerebrovascular Autoregulation in Intracranial Hypertension.

PubMed

Bragin, Denis E; Statom, Gloria; Nemoto, Edwin M

2016-01-01

We previously suggested that the discrepancy between a critical cerebral perfusion pressure (CPP) of 30 mmHg, obtained by increasing intracranial pressure (ICP), and 60 mmHg, obtained by decreasing arterial pressure, was due to pathological microvascular shunting at high ICP [1], and that the determination of the critical CPP by the static cerebral blood flow (CBF) autoregulation curve is not valid with intracranial hypertension. Here, we demonstrated that induced dynamic ICP reactivity (iPRx), and cerebrovascular reactivity (CVRx) tests accurately identify the critical CPP in the hypertensive rat brain, which differs from that obtained by the static autoregulation curve. Step changes in CPP from 70 to 50 and 30 mmHg were made by increasing ICP using an artificial cerebrospinal fluid reservoir connected to the cisterna magna. At each CPP, a transient 10-mmHg increase in arterial pressure was induced by bolus intravenous dopamine. iPRx and iCVRx were calculated as ΔICP/Δ mean arterial pressure (MAP) and as ΔCBF/ΔMAP, respectively. The critical CPP at high ICP, obtained by iPRx and iCVRx, is 50 mmHg, where compromised capillary flow, transition of blood flow to nonnutritive microvascular shunts, tissue hypoxia, and brain-blood barrier leakage begin to occur, which is higher than the 30 mmHg determined by static autoregulation.

Preventive role of social interaction for cocaine conditioned place preference: correlation with FosB/DeltaFosB and pCREB expression in rat mesocorticolimbic areas

PubMed Central

El Rawas, Rana; Klement, Sabine; Salti, Ahmad; Fritz, Michael; Dechant, Georg; Saria, Alois; Zernig, Gerald

2012-01-01

The worsening of drug abuse by drug-associated social interaction is a well-studied phenomenon. In contrast, the molecular mechanisms of the beneficial effect of social interaction, if offered as a mutually exclusive choice to drugs of abuse, are under-investigated. In a rat place preference conditioning (CPP) paradigm, four 15 min episodes of social interaction with a gender- and weight-matched male early-adult conspecific inhibited cocaine-induced reinstatement of cocaine CPP, a model of relapse. These protective effects of social interaction were paralleled by a reduced activation, as assessed by Zif268 expression, in brain areas known to play pivotal roles in drug-seeking behavior. Here we show that social interaction during extinction of cocaine CPP also reduced cocaine-CPP-stimulated FosB expression in the nucleus accumbens shell and core. In addition, social interaction during cocaine CPP extinction increased pCREB (cAMP response element binding protein) expression in the nucleus accumbens shell and the cingulate cortex area 1 (Cg1). Our results show that FosB and pCREB may be implicated in the protective effect of social interaction against cocaine-induced reinstatement of CPP. Thus, social interaction, if offered in a context that is clearly distinct from the previously drug-associated one, may profoundly inhibit relapse to cocaine addiction. PMID:22403532

Lactosylated casein phosphopeptides as specific indicators of heated milks.

PubMed

Pinto, Gabriella; Caira, Simonetta; Cuollo, Marina; Fierro, Olga; Nicolai, Maria Adalgisa; Chianese, Lina; Addeo, Francesco

2012-02-01

Casein phosphopeptides (CPP) were identified in small amounts in milks heated at various intensities by using matrix-assisted laser desorption/ionization (MALDI) time-of-flight mass spectrometry. CPP selectively concentrated on hydroxyapatite (HA) were regenerated using phosphoric acid mixed in the matrix. Unphosphorylated peptides not retained by HA were removed by buffer washing. This procedure enhanced the MALDI signals of CPP that are ordinarily suppressed by the co-occurrence of unphosphorylated peptides. CPP, belonging to the β-casein (CN) family, i.e., (f1-29) 4P, (f1-28) 4P, and (f1-27) 4P, and the α(s2)-CN family, i.e., (f1-21) 4P and (f1-24) 4P, were observed in liquid and powder milk. The lactosylated counterparts were specific to intensely heated milks, but absent in raw and thermized/pasteurized milk. Most CPP with C-terminal lysines probably arose from the activity of plasmin; an enzyme most active in casein hydrolysis. A CPP analogue was used as the internal standard. The raw milk signature peptide β-CN (f1-28) 4P constituted ~4.3% of the total β-CN. Small amounts of lactosylated peptides, which varied with heat treatment intensity, were detected in the milk samples. The limit of detection of ultra-high-temperature milk adjunction in raw or pasteurized milk was ~10%.

Agmatine attenuates acquisition but not the expression of ethanol conditioned place preference in mice: a role for imidazoline receptors.

PubMed

Sameer, Shaikh M; Chakraborty, Suwarna S; Ugale, Rajesh R

2013-04-01

The present study investigated the effect of agmatine on acquisition and expression of ethanol conditioned place preference (CPP) and its modulation by imidazoline agents. Swiss albino mice were treated intraperitoneally with saline or agmatine (20-40 mg/kg) before injection of ethanol (1.25 mg/kg) during conditioning days or on a test day (20-120 mg/kg), to observe the effect on acquisition or expression of CPP, respectively. Agmatine inhibited the acquisition but not the expression of ethanol CPP. Furthermore, both the I₁ receptor antagonist, efaroxan (9 mg/kg) and the I₂ receptor antagonist, BU224 (5 mg/kg) attenuated the agmatine-induced inhibition of the ethanol CPP acquisition. In contrast, the I₂ receptor agonist, 2-BFI (5 mg/kg) and I₁ receptor agonist, moxonidine (0.4 mg/kg) alone, or a combination of their subeffective doses, significantly attenuated the effect of agmatine (20 mg/kg) on acquisition of ethanol CPP. Agmatine or imidazoline agents alone produced neither place preference nor aversion, and at the doses used in the present study did not affect locomotor activity. Thus, agmatine attenuates the acquisition of ethanol CPP at least in part by imidazoline (I₁ or I₂) receptors. In future studies, agmatine or agents acting at the imidazoline receptors could be explored for their therapeutic potential in ethanol dependence.

Blocking α4β2 and α7 nicotinic acetylcholine receptors inhibits the reinstatement of morphine-induced CPP by drug priming in mice.

PubMed

Feng, Bin; Xing, Jiang-hao; Jia, Dong; Liu, Shui-bing; Guo, Hong-ju; Li, Xiao-qiang; He, Xiao-sheng; Zhao, Ming-gao

2011-06-20

Investigating the interaction between nicotinic and opioid receptors is of great interest for both basic mechanistic and clinical reasons. Morphine and nicotine, two common drugs of abuse, share several behavioral and rewarding properties. However, little is known about the subtypes of nicotinic acetylcholine receptors (nAChR) in the reinstatement of morphine-induced conditioned place preference (CPP). In this study, we found that a non-specific nAChR agonist, nicotine (0.5mg/kg), had no effects on the reinstatement of morphine-induced CPP. However, we found that pretreatment with specific α(4)β(2) and α(7) nAChR subtype antagonists, dihydroxy-β-erithroidine (DHβE, 5mg/kg) and methyllycaconitine (MLA, 4 mg/kg), 20 min prior to administration of morphine, inhibited the reinstatement of morphine-induced CPP by drug priming in mice. Furthermore, depression of the reinstatement of morphine-induced CPP by a single DHβE or MLA treatment lasted at least three days later when the reinstatement was induced by morphine priming. The data suggest that specific nAChR subtypes, i.e., α(4)β(2) and α(7), may contribute to the reinstatement of morphine-induced CPP by drug priming in mice. Copyright © 2011 Elsevier B.V. All rights reserved.

Attachment Security Mediates the Longitudinal Association Between Child-Parent Psychotherapy and Peer Relations for Toddlers of Depressed Mothers

PubMed Central

Guild, Danielle J.; Toth, Sheree L.; Handley, Elizabeth D.; Rogosch, Fred A.; Cicchetti, Dante

2017-01-01

Numerous investigations have demonstrated that Child-Parent Psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of post-intervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined post-intervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (DC; n = 55). A prior investigation with this sample indicated that offpring who received CPP attained significantly higher rates of secure attachment post-intervention, wheras insecure attachment continued to predominate for offspring in the DC group. The present study examined follow-up data of teachers’ reports on participants’ competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at post-intervention, which in turn was associated with more positive peer relationships at age 9. PMID:28401848

Attachment security mediates the longitudinal association between child-parent psychotherapy and peer relations for toddlers of depressed mothers.

PubMed

Guild, Danielle J; Toth, Sheree L; Handley, Elizabeth D; Rogosch, Fred A; Cicchetti, Dante

2017-05-01

Numerous investigations have demonstrated that child-parent psychotherapy (CPP) promotes secure attachment between mothers and offspring. However, the role of postintervention attachment security as it relates to long-term child outcomes has never been evaluated. The present study therefore examined postintervention attachment status as a mediator of the association between CPP for depressed mothers and their offspring and subsequent peer relations among offspring. Depressed mothers and their toddlers were randomized to receive CPP (n = 45) or to a control group (n = 55). A prior investigation with this sample indicated that offspring who received CPP attained significantly higher rates of secure attachment postintervention, whereas insecure attachment continued to predominate for offspring in the control group. The present study examined follow-up data of teachers' reports on participants' competence with classroom peers when they were approximately 9 years old. Findings indicated that children who received CPP were more likely to evidence secure attachments at postintervention, which in turn was associated with more positive peer relationships at age 9.

CPP-TRS(C): On using visual cognitive symbols to enhance communication effectiveness

NASA Technical Reports Server (NTRS)

Tonfoni, Graziella

1994-01-01

Communicative Positioning Program/Text Representation Systems (CPP-TRS) is a visual language based on a system of 12 canvasses, 10 signals and 14 symbols. CPP-TRS is based on the fact that every communication action is the result of a set of cognitive processes and the whole system is based on the concept that you can enhance communication by visually perceiving text. With a simple syntax, CPP-TRS is capable of representing meaning and intention as well as communication functions visually. Those are precisely invisible aspects of natural language that are most relevant to getting the global meaning of a text. CPP-TRS reinforces natural language in human machine interaction systems. It complements natural language by adding certain important elements that are not represented by natural language by itself. These include communication intention and function of the text expressed by the sender, as well as the role the reader is supposed to play. The communication intention and function of a text and the reader's role are invisible in natural language because neither specific words nor punctuation conveys them sufficiently and unambiguously; they are therefore non-transparent.

Galnon Facilitates Extinction of Morphine-Conditioned Place Preference but Also Potentiates the Consolidation Process

PubMed Central

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R.; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process. PMID:24146862

Galnon facilitates extinction of morphine-conditioned place preference but also potentiates the consolidation process.

PubMed

Zhao, Xiaojie; Yun, Keming; Seese, Ronald R; Wang, Zhenyuan

2013-01-01

Learning and memory systems are intimately involved in drug addiction. Previous studies suggest that galanin, a neuropeptide that binds G-protein coupled receptors, plays essential roles in the encoding of memory. In the present study, we tested the function of galnon, a galanin receptor 1 and 2 agonist, in reward-associated memory, using conditioned place preference (CPP), a widely used paradigm in drug-associated memory. Either before or following CPP-inducing morphine administration, galnon was injected at four different time points to test the effects of galanin activation on different reward-associated memory processes: 15 min before CPP training (acquisition), immediately after CPP training (consolidation), 15 min before the post-conditioning test (retrieval), and multiple injection after post-tests (reconsolidation and extinction). Galnon enhanced consolidation and extinction processes of morphine-induced CPP memory, but the compound had no effect on acquisition, retrieval, or reconsolidation processes. Our findings demonstrate that a galanin receptor 1 and 2 agonist, galnon, may be used as a viable compound to treat drug addiction by facilitating memory extinction process.

Synthesis of β-Calcium Pyrophosphate by sol-gel method

NASA Astrophysics Data System (ADS)

Windarti, T.; Taslimah; Haris, A.; Astuti, Y.; Darmawan, A.

2017-02-01

Beta calcium pyrophosphate [β-CPP, β-Ca2P2O7] can be used as bone graft extender in posterolateral lumbar fusion. In this research, β-CPP was synthesized by sol-gel method using phosphorus pentaoxide [P2O5] and calcium nitrate tetrahydrate [Ca(NO3)2.4H2O] as phosphorus and calcium precursors. The reaction was carried out in ethanol medium with Ca/P ratio of 1.67. After 21 hours of reaction and 20 hours of drying at 80°C, white powder of amorphous calcium phosphate (ACP) was produced. Transformation of ACP to β-CPP was undertaken by firring at 400-800°C for 8 hours. Transformations of amorphous to microcrystalline, semicrystalline and crystalline structures occur at 400, 600 and 800°C, respectively. The β-CPP with the crystallite size of 61.71 nm, Ca/P ratio of 0.89 and Ca/O ratio of 0.21 was achieved by firing at 800°C. Morphology changes due to firing in which irregular shape of β-CPP at 400° changed to regular cuboid at 600 °C and above.

Facilitation of Memory for Extinction of Drug-Induced Conditioned Reward: Role of Amygdala and Acetylcholine

PubMed Central

Schroeder, Jason P.; Packard, Mark G.

2004-01-01

These experiments examined the effects of posttrial peripheral and intra-amygdala injections of the cholinergic muscarinic receptor agonist oxotremorine on memory consolidation underlying extinction of amphetamine conditioned place preference (CPP) behavior. Male Long-Evans rats were initially trained and tested for an amphetamine (2 mg/kg) CPP. Rats were subsequently given limited extinction training, followed by immediate posttrial peripheral or intrabasolateral amygdala injections of oxotremorine. A second CPP test was then administered, and the amount of time spent in the previously amphetamine-paired and saline-paired apparatus compartments was recorded. Peripheral (0.07 or 0.01 mg/kg) or intra-amygdala (10 ηg/0.5μL) postextinction trial injections of oxotremorine facilitated CPP extinction. Oxotremorine injections that were delayed 2 h posttrial training did not enhance CPP extinction, indicating a time-dependent effect of the drug on memory consolidation processes. The findings indicate that memory consolidation for extinction of approach behavior to environmental stimuli previously paired with drug reward can be facilitated by posttrial peripheral or intrabasolateral amygdala administration of a cholinergic agonist. PMID:15466320

Preparation and bioactive properties of chitosan and casein phosphopeptides composite coatings for orthopedic implants.

PubMed

Qin, Liguo; Dong, Huanhuan; Mu, Ziqing; Zhang, Yali; Dong, Guangneng

2015-11-20

Using the layer-by-layer deposition method, functional chitosan/casein phospopeptides (CS/CPP) composite coatings were produced on Co-Cr-Mo alloy. The CS/CPP composite coatings had the dendritic topography, and were quite hydrophilic. Zeta potential measurements showed the composite coatings were negative charged at neural pH. XPS results indicated that the CS/CPP composite coatings were covalently bond to the substrate. When MC3T3-E1 cells were seeded on the CS/CPP composite coatings, no cytotoxicity was observed. The bone morphogenetic protein-2 (BMP-2) mRNA expression was significantly up-regulated in MC3T3-E1 cells cultured on the composite coatings and it was twice as much as that of cells cultured on the bare substrate. The expression of osteoprotegerin (OPG) mRNA and the ratio of OPG/receptor activator of nuclear factor-κB ligand (RNAKL) mRNA were increased 5-fold and 55-fold, respectively. These results suggested the CS/CPP composite coatings may have potential application in cobalt matrix orthopaedic implants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Insulin Resistance of Puberty.

PubMed

Kelsey, Megan M; Zeitler, Philip S

2016-07-01

Puberty is a time of considerable metabolic and hormonal change. Notably, puberty is associated with a marked decrease in insulin sensitivity, on par with that seen during pregnancy. In otherwise healthy youth, there is a nadir in insulin sensitivity in mid-puberty, and then it recovers at puberty completion. However, there is evidence that insulin resistance (IR) does not resolve in youth who are obese going into puberty and may result in increased cardiometabolic risk. Little is known about the underlying pathophysiology of IR in puberty, and how it might contribute to increased disease risk (e.g., type 2 diabetes). In this review, we have outlined what is known about the IR in puberty in terms of pattern, potential underlying mechanisms and other mediating factors. We also outline other potentially related metabolic changes that occur during puberty, and effects of underlying insulin resistant states (e.g., obesity) on pubertal changes in insulin sensitivity.

Noncovalent interaction-assisted drug delivery system with highly efficient uptake and release of paclitaxel for anticancer therapy.

PubMed

Wei, Yuping; Ma, Liang; Zhang, Liang; Xu, Xia

2017-01-01

An effective drug delivery system requires efficient drug uptake and release inside cancer cells. Here, we report a novel drug delivery system, in which paclitaxel (PTX) interacts with a novel cell penetrating peptide (CPP) through noncovalent interaction designed based on molecular simulations. This CPP/PTX complex confers high efficiency in delivering PTX into cancer cells not by endocytosis but by an energy-independent pathway. Once inside cells, the noncovalent interaction between PTX and the CPP may allow fast release of PTX within cells due to the direct translocation of CPP/PTX. This drug delivery system exhibits strong capacity for inhibition of tumor growth and offers a new avenue for the development of advanced drug delivery systems for anticancer therapy.

Studies of proteoglycan involvement in CPP-mediated delivery.

PubMed

Wittrup, Anders; Zhang, Si-He; Belting, Mattias

2011-01-01

Cell-penetrating peptides (CPPs) are widely used to deliver macromolecular cargoes to intracellular sites of action. Many CPPs have been demonstrated to rely on cell surface heparan sulfate proteoglycans (HSPGs) for efficient cellular entry and delivery. In this chapter, we describe methods for the study of PG involvement in CPP uptake. We provide descriptions of how to determine whether uptake of a CPP of interest is dependent on PGs. We also provide detailed protocols for the purification of PGs by anion-exchange chromatography as well as the characterization of the HSPG core protein composition of a cell line of interest. Finally, we present methods for modulating the expression level of specific HSPG core proteins as a means to determine the core protein specificity in the uptake of a particular CPP.

A child with pituitary gigantism and precocious adrenarche: does GH and/or PRL advance the onset of adrenarche?

PubMed

Iwatani, N; Kodama, M; Seto, H

1992-06-01

We describe a female child with pituitary gigantism and precocious adrenarche. From two years of age she showed unusual overgrowth, and at 5 years old she was 133.5 cm (+ 5.5 SD) tall and weighed 40.5 kg. Her precocious manifestations were public hair, acne vulgaris, hirsutism, and advanced bone age. Endocrinological examination revealed markedly increased serum growth hormone (GH) and prolactin (PRL), which responded paradoxically to a TRH test. In addition, the concentrations of serum dehydroepiandrosterone (DHA) and its sulfate (DHAS) were increased to adult levels, moving in accordance with changes in ACTH, which suggested that these androgens were secreted from the adrenal glands functionally. These androgens seemed to be responsible for her partial precocity. Prior reports have suggested that GH and/or PRL overproduction might have played a role in the induction of adrenarche. Also, in previous reports of 9 gigantism patients under 10 years old, the manifestation of precocious adrenarche was suggested in 8. Further investigation of the influence of GH and PRL on adrenal androgen production in children with pituitary gigantism is required. On the other hand, in short children with normal GH secretion, attention should be paid to whether or not the GH therapy in early childhood induces precocious adrenarche.

Evolutionary consequence of a change in life cycle complexity: A link between precocious development and evolution toward female-biased sex allocation in a hermaphroditic parasite.

PubMed

Kasl, Emily L; McAllister, Chris T; Robison, Henry W; Connior, Matthew B; Font, William F; Criscione, Charles D

2015-12-01

The evolutionary consequences of changes in the complex life cycles of parasites are not limited to the traits that directly affect transmission. For instance, mating systems that are altered due to precocious sexual maturation in what is typically regarded as an intermediate host may impact opportunities for outcrossing. In turn, reproductive traits may evolve to optimize sex allocation. Here, we test the hypothesis that sex allocation evolved toward a more female-biased function in populations of the hermaphroditic digenean trematode Alloglossidium progeneticum that can precociously reproduce in their second hosts. In these precocious populations, parasites are forced to self-fertilize as they remain encysted in their second hosts. In contrast, parasites in obligate three-host populations have more opportunities to outcross in their third host. We found strong support that in populations with precocious development, allocation to male resources was greatly reduced. We also identified a potential phenotypically plastic response in a body size sex allocation relationship that may be driven by the competition for mates. These results emphasize how changes in life cycle patterns that alter mating systems can impact the evolution of reproductive traits in parasites. © 2015 The Author(s). Evolution © 2015 The Society for the Study of Evolution.

Effects of carrot pomace powder and a mixture of pectin and xanthan on the quality of gluten-free batter and cakes.

PubMed

Majzoobi, Mahsa; Vosooghi Poor, Zahra; Mesbahi, Gholamreza; Jamalian, Jalal; Farahnaky, Asgar

2017-12-01

Carrot pomace powder (CPP) is a valuable by-product of carrot processing containing nutrients and fiber and can be utilized for enrichment of gluten-free products. The main purpose of this study was to determine the effects of various levels of CPP (0, 10, 20, and 30%) and a mixture of hydrocolloids (HC) including pectin and xanthan (1.5% of each) on the quality of batter and gluten-free cakes. With increasing the level of CPP and inclusion of HC the viscosity of the batter increased significantly from 87 mPa s for the control to >7000 mPa s for 30%CCP + HC sample. The density of the control batter was 1.2 g/cm 3 which reduced significantly to 0.899 g/cm 3 for HC sample. The pH of the cake reduced from 7.23 to 6.78 with addition of CPP but increased slightly with inclusion of HC. The density of the cake reduced from 0.510 g/cm 3 for the control to 0.395 g/cm 3 for 20%CCP + C sample. The texture of the cakes became softer, more springy and chewable with addition of CPP, CPP + HC, and HC. The control sample had the lowest uniformity index (0.178) which improved with addition of CPP and CPP + HC and a highly uniform cake with a uniformity index of 0.045 was obtained for the 30%CCP + HC cake. Addition of CPP increased the dark color of the cakes while inclusion of HC had no effect on the appearance of the cake and color. It was concluded that inclusion of maximum 30%CCP and 20%CPP + HC promoted the quality and sensory attributes of gluten-free cakes. Although different types of gluten-free products are available in the market, most of them contain insufficient amount of fiber and nutrients. Despite popularity, gluten-free cakes are poor in fiber and nutrient contents. Therefore, improving the nutritional value of these products has received an increasing attention by the food industry. Carrot pomace powder (CPP) is an available source of fiber and nutrients and hence can be utilized for enrichment of gluten-free products. This study showed that the inclusion of up to 30% CPP or 20% CPP with a mixture of xanthan and pectin (3%, 1:1) improved the quality and sensory attributes of the cakes. Industrial implications of this study may lead to new product development and improved marketing due to the enhancement of quality, sensory attributes, and nutritional value of the products. © 2017 Wiley Periodicals, Inc.

Puberty and Its Measurement: A Decade in Review

ERIC Educational Resources Information Center

Dorn, Lorah D.; Biro, Frank M.

2011-01-01

Since the early 1980s, the focus on the importance of puberty to adolescent development has continued with variability in the methodology selected to measure puberty. To capture the relevant and important issues regarding the measurement of puberty in the last decade, this paper will address (1) the neuroendocrine aspects of puberty and its…

Philosophically Precocious Individuals and Their Developmental Strategies.

ERIC Educational Resources Information Center

Bai, Wenyu

This study interviewed five philosophically precocious individuals (PPIs), four Chinese and one American, to examine their development. Theoretical frameworks used to evaluate data were the Transcendence Evolution Model and the taxonomy of developmental strategies. The Transcendence Evolution Model posits that children's different developmental…

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora.

PubMed

Patel, Ravi R; Sundin, George W; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora . We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora . The minimal inhibitory concentration (MIC) of anti- acpP -CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti- acpP -CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti- acpP -CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti- acpP -CPP1 has more specific antimicrobial effect against E. amylovora . In summary, we demonstrated that PNA-CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control.

Exploration of Using Antisense Peptide Nucleic Acid (PNA)-cell Penetrating Peptide (CPP) as a Novel Bactericide against Fire Blight Pathogen Erwinia amylovora

PubMed Central

Patel, Ravi R.; Sundin, George W.; Yang, Ching-Hong; Wang, Jie; Huntley, Regan B.; Yuan, Xiaochen; Zeng, Quan

2017-01-01

Erwinia amylovora is a Gram-negative bacterial plant pathogen in the family Enterobacteriaceae and is the causal agent of fire blight, a devastating disease of apple and pear. Fire blight is traditionally managed by the application of the antibiotic streptomycin during bloom, but this strategy has been challenged by the development and spread of streptomycin resistance. Thus, there is an urgent need for effective, specific, and sustainable control alternatives for fire blight. Antisense antimicrobials are oligomers of nucleic acid homologs with antisense sequence of essential genes in bacteria. The binding of these molecules to the mRNA of essential genes can result in translational repression and antimicrobial effect. Here, we explored the possibility of developing antisense antimicrobials against E. amylovora and using these compounds in fire blight control. We determined that a 10-nucleotide oligomer of peptide nucleic acid (PNA) targeting the start codon region of an essential gene acpP is able to cause complete growth inhibition of E. amylovora. We found that conjugation of cell penetrating peptide (CPP) to PNA is essential for the antimicrobial effect, with CPP1 [(KFF)3K] being the most effective against E. amylovora. The minimal inhibitory concentration (MIC) of anti-acpP-CPP1 (2.5 μM) is comparable to the MIC of streptomycin (2 μM). Examination of the antimicrobial mechanisms demonstrated that anti-acpP-CPP1 caused dose-dependent reduction of acpP mRNA in E. amylovora upon treatment and resulted in cell death (bactericidal effect). Anti-acpP-CPP1 (100 μM) is able to effectively limit the pathogen growth on stigmas of apple flowers, although less effective than streptomycin. Finally, unlike streptomycin that does not display any specificity in inhibiting pathogen growth, anti-acpP-CPP1 has more specific antimicrobial effect against E. amylovora. In summary, we demonstrated that PNA–CPP can cause an effective, specific antimicrobial effect against E. amylovora and may provide the basis for a novel approach for fire blight control. PMID:28469617

The relationship between obesity and body compositions with respect to the timing of puberty in Chongqing adolescents: a cross-sectional study.

PubMed

He, Fang; Guan, Peiyu; Liu, Qin; Crabtree, Donna; Peng, Linli; Wang, Hong

2017-08-18

It is well known that excess adiposity during childhood may influence pubertal development. However, the extent to which body compositions vary in throughout puberty in boys and girls is currently unknown. The aim of this study was to investigate whether obesity and body compositions correlate with the timing of puberty in boys and girls. By random cluster sampling, our study analyzed data from 1472 students (690 girls, 782 boys) aged 6-17 years from two schools in the Chongqing area. Data were collected by physical examination of weight, height, and skinfold thicknesses. Testicular volume was measured in boys and breast development in girls. By which we got the indicators of obesity, timing of puberty and body compositions. Probit regression analysis was used to group subjects into early puberty (>P 25 ), on-time puberty (P 25  ~ P 75 ), and delayed puberty (

 0.05). In girls, delayed puberty was negatively correlated with Obesity, percentage of body fat, fat mass and fat-free mass, and positively correlated with body density. But in boys, delayed puberty was only negatively correlated with Obesity, the relation between puberty and body compositions was not found.

Hypothalamic hamartoma: is the epileptogenic zone always hypothalamic? Arguments for independent (third stage) secondary epileptogenesis.

PubMed

Scholly, Julia; Valenti, Maria-Paola; Staack, Anke M; Strobl, Karl; Bast, Thomas; Kehrli, Pierre; Steinhoff, Bernhard J; Hirsch, Edouard

2013-12-01

Gelastic seizures associated with hypothalamic hamartomas (HHs) are a clinicoradiologic syndrome presenting with a variety of symptoms, including pharmacoresistant epilepsy with multiple seizure types, electroencephalography (EEG) abnormalities, precocious puberty, behavioral disturbances, and progressive cognitive deterioration. Surgery in adults provides seizure freedom in only one third of patients. The poor results of epilepsy surgery could be explained by an extrahypothalamic epileptogenic zone. The existence of an independent, secondary epileptogenic area with persistent seizures after resection of the presumably primary lesion supports the concept of a "hypothalamic plus" epilepsy. "Hypothalamic plus" epilepsy could be related to either an extrahypothalamic structural lesion (visible on magnetic resonance imaging [MRI] or on neuropathology) or if the former is absent, to a functional alteration with enhanced epileptogenic properties due to a process termed secondary epileptogenesis. We report two patients with gelastic seizures with HH (gelastic seizures isolated or associated with dyscognitive seizures of temporal origin). Both patients underwent two-step surgery: first an endoscopic resection of the HH, followed at a later time by temporal lobectomy. Both patients became seizure-free only after the temporal lobectomy. In both cases, neuropathology failed to demonstrate a significant structural lesion in the temporal lobe. To our knowledge, for the first time, these two cases suggest the existence of independent secondary epileptogenesis in humans. Wiley Periodicals, Inc. © 2013 International League Against Epilepsy.

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

PubMed Central

Millar, Robert P.; Pawson, Adam J.; Morgan, Kevin; Rissman, Emilie F.; Lu, Zhi-Liang

2009-01-01

Geoffrey Wingfield Harris’ demonstration of hypothalamic hormones regulating pituitary function led to their structural identification and therapeutic utilization in a wide spectrum of diseases. Amongst these, Gonadotropin Releasing Hormone (GnRH) and its analogs are widely employed in modulating gonadotropin and sex steroid secretion to treat infertility, precocious puberty and many hormone-dependent diseases including endometriosis, uterine fibroids and prostatic cancer. While these effects are all mediated via modulation of the pituitary gonadotrope GnRH receptor and the Gq signaling pathway, it has become increasingly apparent that GnRH regulates many extrapituitary cells in the nervous system and periphery. This review focuses on two such examples, namely GnRH analog effects on reproductive behaviors and GnRH analog effects on the inhibition of cancer cell growth. For both effects the relative activities of a range of GnRH analogs is distinctly different from their effects on the pituitary gonadotrope and different signaling pathways are utilized. As there is only a single functional GnRH receptor type in man we have proposed that the GnRH receptor can assume different conformations which have different selectivity for GnRH analogs and intracellular signaling proteins complexes. This ligand-induced selective-signaling recruits certain pathways while by-passing others and has implications in developing more selective GnRH analogs for highly specific therapeutic intervention. PMID:17976709

Congenital Hypothalamic "Hamartoblastoma" Versus "Hamartoma": Suggestions for Neuropathologic Terminology Emanating From a Mid-gestational Autopsy Case of Pallister-Hall Syndrome.

PubMed

Dunham, C; McFadden, D; Dahlgren, L; Butler, B; Hamilton, S; McKinnon, M

2018-01-01

Pallister-Hall syndrome (PHS) is a rare malformative disorder that is due to truncating functional repressor mutations in GLI3. Since the seminal publication in 1980, hypothalamic tumors have been recognized to be a cardinal feature of PHS. In their original description of the neuropathologic features of PHS, Clarren et al. coined the term "hamartoblastoma" to characterize what they deemed to be a dual malformative and neoplastic mass of the hypothalamus. In subsequent published cases/series of PHS, the term "hamartoma" was often substituted for hamartoblastoma given what appeared to be a benign natural history of this lesion. Additional confusion in the literature has ensued since most hypothalamic hamartomas (HH) encountered on the clinical neuropathology service are "isolated" in nature (ie, no other congenital malformations) and present in a very different and stereotypical fashion with gelastic seizures and/or precocious puberty. While genomic investigations of isolated HH have begun to uncover a mutational profile of these cases, GLI3 mutations have only been recognized in a small subset of isolated HH. Herein, we describe the autopsy findings from a 21-week gestational age fetus with features of PHS. Moreover, we provide a detailed description of the hypothalamic tumor affecting this fetus and propose a novel subclassification of HH, distinguishing syndromic from isolated forms based upon the presence or absence of neocortical-like areas.

Puberty.

PubMed

Biro, Frank M

2007-12-01

Puberty consists of interrelated biological changes and occurs at a time when the individual also encounters cognitive and social changes. In this article we examine our current knowledge regarding the onset of puberty, the sequence and timing of puberty, and medical issues and physiologic changes that may arise with pubertal maturation. Figures included demonstrate the sexual maturation stages and interrelationships between the various parameters of puberty.

No evidence that environmental enrichment during rearing protects against cocaine behavioral effects but as an intervention reduces an already established cocaine conditioned place preference.

PubMed

Galaj, E; Shukur, A; Manuszak, M; Newman, K; Ranaldi, R

2017-05-01

Environmental enrichment (EE) produces differential effects on psychostimulant-related behaviors. Therefore, we investigated whether the timing of EE exposure - during rearing and before cocaine exposure versus in adulthood and after cocaine exposure might be a determining factor. In Experiment 1, rats reared with EE or not (non-EE) were conditioned with cocaine (5, 10 or 20mg/kg) in one compartment of a CPP apparatus and saline in the other, and later tested for cocaine CPP. In Experiment 2, locomotor activity in response to repeated injections of saline or cocaine was measured in rats raised with EE or non-EE. In Experiment 3 we measured the effects of EE or non-EE during rearing on food-based conditioned approach learning. In Experiment 4, rats were exposed to cocaine CPP conditioning then underwent 60days of EE or non-EE treatment after which they were tested for cocaine CPP. Our results show that rearing in EE did not reduce cocaine CPP or cocaine-induced locomotor activity (Experiments 1 and 2) but significantly facilitated conditioned approach learning (Experiment 3). On the other hand, EE treatment introduced after cocaine conditioning significantly reduced the expression of cocaine CPP (Experiment 4). These findings suggest that EE does not protect against cocaine's rewarding and stimulant effects but can reduce already established cocaine effects, suggesting that EE might be an effective treatment for cocaine addiction-related behaviors. Copyright © 2017 Elsevier Inc. All rights reserved.

Acquisition and reinstatement of ethanol-induced conditioned place preference in rats: Effects of the cholinesterase inhibitors donepezil and rivastigmine.

PubMed

Gawel, Kinga; Labuz, Krzysztof; Gibula-Bruzda, Ewa; Jenda, Malgorzata; Marszalek-Grabska, Marta; Silberring, Jerzy; Kotlinska, Jolanta H

2016-07-01

The present study examined the influence of the cholinesterase inhibitors donepezil (a selective inhibitor of acetylcholinesterase) and rivastigmine (also an inhibitor of butyrylcholinesterase) on the acquisition and reinstatement of ethanol-induced conditioned place preference (CPP) in rats. Before the CPP procedure, animals received a single injection of ethanol (0.5 g/kg, 10% w/v, intraperitoneally [i.p.]) for 15 days. The ethanol-induced CPP (biased method) was developed by four injections of ethanol (0.5 g/kg, 10% w/v, i.p.) every second day. Control rats received saline instead of ethanol. Donepezil (0.5, 1 or 3 mg/kg, i.p.) or rivastigmine (0.03, 0.5 or 1 mg/kg, i.p.) were administered before ethanol during conditioning or before the reinstatement of ethanol-induced CPP. The cholinesterase inhibitors were equally effective in increasing (dose dependently) the acquisition of ethanol-induced CPP. Furthermore, priming injections of both inhibitors reinstated (cross-reinstatement) the ethanol-induced CPP with similar efficacy. These effects of both cholinesterase inhibitors were reversed by mecamylamine (3 mg/kg, i.p.), a nicotinic acetylcholine receptor antagonist, but not by scopolamine (0.5 mg/kg, i.p.), a muscarinic acetylcholine receptor antagonist. Thus, our results show that the cholinergic system is involved in the reinforcing properties of ethanol, and nicotinic acetylcholine receptors play an important role in the relapse to ethanol-seeking behaviour. © The Author(s) 2016.

Global ischemia in dogs: cerebrovascular CO2 reactivity and autoregulation.

PubMed

Nemoto, E M; Snyder, J V; Carroll, R G; Morita, H

1975-01-01

One hypothesis on the pathogenesis of post-ischemic-anoxic encephalopathy is impaired cerebral perfusion or the no-reflow phenomenon. Therapies aimed at preventing the development of this phenomenon are increased cerebral perfusion pressure (CPP) and hyperventilation or hypercapnia. Using a dog model in which we have described the progressive development of post-ischemic (PI) cerebral hypoperfusion after 15 minutes of global ischemia induced by aortic and vena cavae clamping, our aims in this study were to determine during the PI cerebral hypoperfusion period: (1) cerebrovascular reactivity to CO2, and (2) cerebral blood (CBF) autoregulation. Post-ischemic cerebral hypoperfusion to about 50% of normal was not accompanied by raised intracranial pressure (ICP) but cerebrovascular CO2 reactivity was markedly attenuated while maintaining some kind of autoregulatory phenomenon. Cerebral uptake of oxygen was not significantly affected by changing PACO2 from 20 to 60 torr at constant CPP or by changing CPP from 64 to 104 torr at constant PaCO2. These results suggest that increasing both CPP and hypocapnia/hypercapnia would not significantly attenuate PI neurological deficit after global cerebral ischemia. However, in two dogs inadvertently hemodiluted in the PI period, increasing CPP from 50 to 200 torr increased CBF by 200%, suggesting that hemodilution plus increased CPP may be effective therapy for amelioration of post-ischemic-anoxic encephalopathy. The significance of our findings on cerebrovascular CO2 reactivity and autoregulation with respect to the mechanism of the no-reflow phenomenon is discussed.

SAXS characterization of the interactions among digested food compounds and the anti-oxidant and anti-inflammatory activities of the formed nanocomplexes.

PubMed

Yang, Yingkang; Wang, Xiaoqi; Chen, Guijie; Zhou, Wenhua; Zeng, Xiaoxiong; Hu, Bing; Li, Yunqi; Huang, Qingrong

2018-06-06

In the present study, small angle X-ray scattering (SAXS) is applied to investigate the interaction between caseinophosphopeptides (CPP), the major digested product of milk protein, and chitosan (CS) under simulated gastrointestinal (GI) pH conditions. The change in pH value from the gastric to small intestinal environment induces complexation between CPP and CS, which is mainly driven by electrostatic interactions. The fractal dimension (Df) value of the domains inside the CPP-CS complexes is greater than 3, indicating the formation of dense particles/aggregates at the nanoscale. The Df value generally increases with an increase in the CS/CPP mass ratio. As a representative of polyphenols, (-)-epigallocatechin gallate (EGCG) associates with CS and CPP, forming nanocomplexes with a spherical shape and average particle size of around 208 nm. The formed CS-EGCG-CPP nanocomplexes do not affect the antioxidant activity of EGCG in the in vitro assays. Moreover, in the cellular assay, the nanocomplexes protect the RAW264.7 cells against H2O2-induced oxidative injury. In addition, the nanocomplexes significantly inhibit the lipopolysaccharide (LPS)-induced production of nitric oxide (NO), TNF-α, IL-1β and IL-6. Furthermore, they inhibit the expression of iNOS, phosphorylation and degradation of IκB, as well as the translocation of NF-κB p65; this indicates that the mechanism for their anti-inflammatory activity is via the mediation of the NF-κB signaling pathway.

The Extracellular Matrix Protein Brevican Limits Time-Dependent Enhancement of Cocaine Conditioned Place Preference.

PubMed

Lubbers, Bart R; Matos, Mariana R; Horn, Annemarie; Visser, Esther; Van der Loo, Rolinka C; Gouwenberg, Yvonne; Meerhoff, Gideon F; Frischknecht, Renato; Seidenbecher, Constanze I; Smit, August B; Spijker, Sabine; van den Oever, Michel C

2016-06-01

Cocaine-associated environmental cues sustain relapse vulnerability by reactivating long-lasting memories of cocaine reward. During periods of abstinence, responding to cocaine cues can time-dependently intensify a phenomenon referred to as 'incubation of cocaine craving'. Here, we investigated the role of the extracellular matrix protein brevican in recent (1 day after training) and remote (3 weeks after training) expression of cocaine conditioned place preference (CPP). Wild-type and Brevican heterozygous knock-out mice, which express brevican at ~50% of wild-type levels, received three cocaine-context pairings using a relatively low dose of cocaine (5 mg/kg). In a drug-free CPP test, heterozygous mice showed enhanced preference for the cocaine-associated context at the remote time point compared with the recent time point. This progressive increase was not observed in wild-type mice and it did not generalize to contextual-fear memory. Virally mediated overexpression of brevican levels in the hippocampus, but not medial prefrontal cortex, of heterozygous mice prevented the progressive increase in cocaine CPP, but only when overexpression was induced before conditioning. Post-conditioning overexpression of brevican did not affect remote cocaine CPP, suggesting that brevican limited the increase in remote CPP by altering neuro-adaptive mechanisms during cocaine conditioning. We provide causal evidence that hippocampal brevican levels control time-dependent enhancement of cocaine CPP during abstinence, pointing to a novel substrate that regulates incubation of responding to cocaine-associated cues.

Combined action of MK-801 and ceftriaxone impairs the acquisition and reinstatement of morphine-induced conditioned place preference, and delays morphine extinction in rats.

PubMed

Fan, Yaodong; Niu, Haichen; Rizak, Joshua D; Li, Ling; Wang, Guimei; Xu, Liqi; Ren, He; Lei, Hao; Yu, Hualin

2012-10-01

It is well established that glutamate and its receptors, particularly the N-methyl-D-aspartate receptor (NMDAR), play a significant role in addiction and that the inhibition of glutamatergic hyperfunction reduces addictive behaviors in experimental animals. Specifically, NMDAR antagonists such as MK-801, and an inducer of the expression of glutamate transporter subtype-1 (GLT-1) (ceftriaxone) are known to inhibit addictive behavior. The purpose of this study was to determine whether the combined action of a low dose of MK-801 and a low dose of ceftriaxone provides better inhibition of the acquisition, extinction, and reinstatement of morphine-induced conditioned place preference (CPP) than either compound alone. A morphine-paired CPP experiment was used to study the effects of low doses of MK-801, ceftriaxone and a combination of both on reward-related memory (acquisition, extinction, and reinstatement of morphine preference) in rats. A low dose of neither MK-801 (0.05 mg/kg, i.p.) nor ceftriaxone (25 mg/kg, i.p.) alone effectively impaired CPP behaviors. However, when applied in combination, they reduced the acquisition of morphine-induced CPP and completely prevented morphine reinstatement. Their combination also notably impaired the extinction of morphine-induced CPP. The combined action of a low dose of an NMDAR antagonist (MK-801) and GLT-1 activation by ceftriaxone effectively changed different phases of CPP behavior.

Cell-penetrating peptide-morpholino conjugates alter pre-mRNA splicing of DMD (Duchenne muscular dystrophy) and inhibit murine coronavirus replication in vivo.

PubMed

Moulton, H M; Fletcher, S; Neuman, B W; McClorey, G; Stein, D A; Abes, S; Wilton, S D; Buchmeier, M J; Lebleu, B; Iversen, P L

2007-08-01

The cellular uptake of PMOs (phosphorodiamidate morpholino oligomers) can be enhanced by their conjugation to arginine-rich CPPs (cell-penetrating peptides). Here, we discuss our recent findings regarding (R-Ahx-R)(4)AhxB (Ahx is 6-aminohexanoic acid and B is beta-alanine) CPP-PMO conjugates in DMD (Duchenne muscular dystrophy) and murine coronavirus research. An (R-Ahx-R)(4)AhxB-PMO conjugate was the most effective compound in inducing the correction of mutant dystrophin transcripts in myoblasts derived from a canine model of DMD. Similarly, normal levels of dystrophin expression were restored in the diaphragms of mdx mice, with treatment starting at the neonatal stage, and protein was still detecTable 22 weeks after the last dose of an (R-Ahx-R)(4)AhxB-PMO conjugate. Effects of length, linkage and carbohydrate modification of this CPP on the delivery of a PMO were investigated in a coronavirus mouse model. An (R-Ahx-R)(4)AhxB-PMO conjugate effectively inhibited viral replication, in comparison with other peptides conjugated to the same PMO. Shortening the CPP length, modifying it with a mannosylated serine moiety or replacing it with the R(9)F(2) CPP significantly decreased the efficacy of the resulting PPMO (CPP-PMO conjugate). We attribute the success of this CPP to its stability in serum and its capacity to transport PMO to RNA targets in a manner superior to that of poly-arginine CPPs.

Molecular evolution of the CPP-like gene family in plants: insights from comparative genomics of Arabidopsis and rice.

PubMed

Yang, Zefeng; Gu, Shiliang; Wang, Xuefeng; Li, Wenjuan; Tang, Zaixiang; Xu, Chenwu

2008-09-01

CPP-like genes are members of a small family which features the existence of two similar Cys-rich domains termed CXC domains in their protein products and are distributed widely in plants and animals but do not exist in yeast. The members of this family in plants play an important role in development of reproductive tissue and control of cell division. To gain insights into how CPP-like genes evolved in plants, we conducted a comparative phylogenetic and molecular evolutionary analysis of the CPP-like gene family in Arabidopsis and rice. The results of phylogeny revealed that both gene loss and species-specific expansion contributed to the evolution of this family in Arabidopsis and rice. Both intron gain and intron loss were observed through intron/exon structure analysis for duplicated genes. Our results also suggested that positive selection was a major force during the evolution of CPP-like genes in plants, and most amino acid residues under positive selection were disproportionately located in the region outside the CXC domains. Further analysis revealed that two CXC domains and sequences connecting them might have coevolved during the long evolutionary period.

Comparing of the Effects of Hypericin and Synthetic Antidepressants on the Expression of Morphine-Induced Conditioned Place Preference

PubMed Central

Assadi, Assad; Zarrindast, Mohammad Reza; Jouyban, Abolghasem; Samini, Morteza

2011-01-01

The effect of hypericin on the expression of morphine-induced conditioned place preference (CPP) was investigated and compared with the effect of the synthetic antidepressants. The CPP paradigms took place over six days using an unbiased procedure. The results demonstrate that intra-peritoneal (IP) injection of morphine sulfate (2.5, 5 and 10 mg/Kg) significantly induce the CPP in rat. Intra-peritoneal and intracerebroventricular (ICV) injection of hypericin and/or synthetic antidepressants augmented morphine-induced CPP. It has been suggested that the adrenergic, serotonergic and dopaminergic neurotransmissions play an important role in mediating the antidepressant effect of hypericin and this effect may be due to its inhibitory effect on the reuptake of neurotransmitters. Morphine produces a reinforcement (reward) effect by activating. The μ-receptors that facilitate dopaminergic transmission. Serotonin is also a potent stimulator of dopamine release in such a way that an increase in brain serotonin could possibly stimulate the dopaminergic system. In conclusion, it may suggest that the augmentation of morphine-induced CPP by hypericin and synthetic antidepressants may be related to the increasing dopamine and serotonin concentrations in synaptic clefts. PMID:24250400

Rational Design of Porous Conjugated Polymers and Roles of Residual Palladium for Photocatalytic Hydrogen Production

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

Li, Lianwei; Cai, Zhengxu; Wu, Qinghe

Developing high efficient photocatalyts for splitting water into oxygen and hydrogen is one of the biggest chemical challenges in solar energy utilization. In this paper, we report our effort in rationally designing conjugated porous polymer (CPP) photocatalysts for photocatalytic hydrogen production (PHP) from water. A series of CPP photocatalysts with different chromophore components and bipyridyl (bpy) contents were synthesized and found to evolve hydrogen photocatalytically from water. The PHP activity of bpy-containing CPPs can be greatly enhanced due to the improved light absorption, better wettability, higher crystallinity and the improved charge separation process. Moreover, the CPP photocatalyst made of strongmore » and fully conjugated donor chromo-phore DBD shows the highest hydrogen production rate ~ 33 μmol/h. The results indicate that copolymerization between a strong donor and weak acceptor is a useful strategy for the devel-opment of efficient photocatalysts. This study clarifies that the residual palladium in the CPP networks plays a key role for the catalytic performance. The PHP activity of CPP photocatalyst can be further enhanced to 164 μmol/h with an apparent quantum yield of 1.8% at 350 nm by loading 2 wt% of extra platinum cocat-alyst.« less

Effects of scopolamine on morphine-induced conditioned place preference in mice.

PubMed

Tan, Hua; Liu, Ning; Wilson, Fraser A W; Ma, Yuanye

2007-09-01

It is well known that the cholinergic system plays a crucial role in learning and memory. Psychopharmacological studies in humans and animals have shown that a systemic cholinergic blockade may induce deficits in learning and memory. Accumulated studies have indicated that learning and memory play an important role in drug addition. In the present study, in order to get a further understanding about the functions of the cholinergic system in drug-related learning and memory, we examined the effects of scopolamine (0.5, 1.0 and 2.0 mg/kg) on morphine-induced conditioned place preference (CPP). Two kinds of morphine exposure durations (4 days and 12 days) were used. The main finding was that all doses of scopolamine enhanced the extinction of morphine-induced CPP in mice treated with morphine for 12 days. However, in mice treated with morphine for 4 days, all doses of scopolamine did not inhibit morphine-induced CPP. The highest dose (2.0 mg/kg) of scopolamine even significantly delayed the extinction of morphine-induced CPP. Our results suggest that the effects of a systemic cholinergic blockade on morphine-induced CPP depend on the morphine exposure time.

GluR2-3Y Inhibits the Acquisition and Reinstatement of Morphine-Induced Conditioned Place Preference in Rats.

PubMed

Lin, Xiao-Jing; Zhang, Jian-Jun; Yu, Long-Chuan

2016-04-01

Accumulating evidence indicates that α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid receptors (AMPARs) are involved in the relapse to abused drugs. However, the role of AMPARs containing the GluR2 subunit in opiate addiction is still unclear. GluR2-3Y, an interfering peptide, prevents the endocytosis of AMPARs containing the GluR2 subunit. In this study, we explored the effect of intravenous injection of GluR2-3Y on the acquisition, expression, and reinstatement of morphine-induced conditioned place preference (mCPP) in rats. We found that infusion of GluR2-3Y (1.5 nmol/g) one hour before morphine during the conditioning phase inhibited the acquisition of mCPP, while an identical injection one hour before the post-conditioning test had no influence on the expression of mCPP. Injection of GluR2-3Y (1.5 nmol/g) after mCPP extinction blocked the morphine-induced reinstatement of mCPP. Our results strongly support the hypothesis that inhibition of AMPAR endocytosis provides a new target for the treatment of opiate addiction.

Inhibition of phosphodiesterase10A attenuates morphine-induced conditioned place preference.

PubMed

Mu, Ying; Ren, Zhaoxiang; Jia, Jia; Gao, Bo; Zheng, Longtai; Wang, Guanghui; Friedman, Eitan; Zhen, Xuechu

2014-09-25

Phosphodiesterase (PDE) 10A is selectively expressed in medium spiny neurons of the striatum. Nucleus accumbens (NAc) is a key region that mediates drug reward and addiction-related behaviors. To investigate the potential role of PDE10A in the reinforcement properties of morphine, we tested the effect of MP-10, a selective inhibitor of PDE10A, on acquisition, expression, and extinction of morphine-induced conditioned place preference (CPP). The results show that 2.5 mg/kg MP-10, administered subcutaneously, significantly inhibited the acquisition of morphine-induced CPP. The same dose of MP-10 alone did not result in the CPP. Moreover, MP-10 did not alter the expression of morphine-induced CPP, but did accelerate the extinction of morphine-induced CPP. Additionally, chronic treatment with 2.5 mg/kg MP-10 decreased expression of phosphorylated CREB (pCREB), activated cAMP response element binding protein, in dorsomedial striatum, in shell of NAc, and in anterior cingulate cortex (ACC) as well as decreased expression of ΔFosB in the shell of NAc and ACC. The results suggest that inhibition of PDE10A may have therapeutic potential in the treatment of opioid addiction.

Effects of CCK-8 on the reinstatement of morphine-induced CPP and expression of behavioral sensitization in rats.

PubMed

Wen, D; Zang, G; Sun, D; Yang, S; Yu, F; Li, S; Ma, C; Cong, B

2013-05-15

Cholecystokinin octapeptide (CCK-8), a neuropeptide, plays an important role in morphine dependence and several addictive behaviors. We have previously reported that CCK-8 attenuates the acquisition of morphine-induced conditioned place preference (CPP), but the possible functions of CCK-8 on drug relapse remain unclear. Here we evaluated the effects of CCK-8 on the reinstatement of extinguished morphine-induced CPP and behavioral sensitization. A single injection of 0.1 and 1μg CCK-8 (i.c.v.) significantly attenuated both drug- (morphine) and stress- (foot shock) primed reinstatement of CPP and reduced the escalated locomotor activity in reinstatement tests. Additionally, CCK-8 blocked the expression of morphine-induced behavioral sensitization. However, administration of CCK-8 (0.01, 0.1 and 1μg) alone to morphine-pretreated rats could not trigger reinstatement of CPP and had no significant effect on threshold sensitivity to foot shock. In conclusion, our study identifies a distinct inhibitory effect of CCK-8 on the reinstatement of drug-seeking behavior and provides a potential application to the medication of drug relapse. Copyright © 2013 IBRO. Published by Elsevier Ltd. All rights reserved.

Precocious glucocorticoid exposure reduces skeletal muscle satellite cells in the fetal rat

USDA-ARS?s Scientific Manuscript database

Perinatal skeletal muscle growth rates are a function of protein and myonuclear accretion. Precocious exposure of the fetus to glucocorticoids (GLC) in utero impairs muscle growth. Reduced muscle protein synthesis rates contribute to this response, but the consequences for myonuclear hyperplasia are...

Pubertal development in children diagnosed with diabetes mellitus type 1 before puberty.

PubMed

Pereira, K C X; Pugliese, B S; Guimarães, M M; Gama, M P

2015-02-01

To investigate an association between pubertal development and timing of menarche with glycemic control, disease duration, and body mass index (BMI) in patients diagnosed with diabetes mellitus type 1 (DM1) before puberty. Retrospective study. The study was performed at the diabetes outpatient clinic of Instituto de Puericultura e Pediatria Martagão Gesteira--IPPMG of the Federal University of Rio de Janeiro--UFRJ. A total of 131 children, 61 girls and 70 boys, diagnosed with DM1 before puberty participated in the study. The study investigated how age at puberty onset relates to mean glycated hemoglobin (HbA1c) before puberty, BMI percentile, and disease duration; how puberty duration relates to mean HbA1c before and during puberty and to disease duration; and how timing of menarche relates to mean HbA1c before puberty, BMI percentile, and disease duration. Age at puberty onset was positively correlated with mean HbA1c before puberty (r = 0.204, R(2) = 0.042; P = .019) and disease duration (r = 0.451, R(2) = 0.203; P < .0001), and negatively correlated with BMI percentile (r = -0.289, R(2) = 0.084; P = .001). Timing of menarche was negatively correlated with BMI percentile (r = -0.556, R(2) = 0.310; P < .001). Children with longer disease duration began puberty later than those diagnosed more recently. Girls in higher BMI percentiles reached menarche sooner.

Evaluating methodological assumptions of a catch-curve survival estimation of unmarked precocial shorebird chickes

USGS Publications Warehouse

McGowan, Conor P.; Gardner, Beth

2013-01-01

Estimating productivity for precocial species can be difficult because young birds leave their nest within hours or days of hatching and detectability thereafter can be very low. Recently, a method for using a modified catch-curve to estimate precocial chick daily survival for age based count data was presented using Piping Plover (Charadrius melodus) data from the Missouri River. However, many of the assumptions of the catch-curve approach were not fully evaluated for precocial chicks. We developed a simulation model to mimic Piping Plovers, a fairly representative shorebird, and age-based count-data collection. Using the simulated data, we calculated daily survival estimates and compared them with the known daily survival rates from the simulation model. We conducted these comparisons under different sampling scenarios where the ecological and statistical assumptions had been violated. Overall, the daily survival estimates calculated from the simulated data corresponded well with true survival rates of the simulation. Violating the accurate aging and the independence assumptions did not result in biased daily survival estimates, whereas unequal detection for younger or older birds and violating the birth death equilibrium did result in estimator bias. Assuring that all ages are equally detectable and timing data collection to approximately meet the birth death equilibrium are key to the successful use of this method for precocial shorebirds.

Maintenance of the Hanford cone penetrometer platform during fiscal year 1999

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

IWATATE, D.F.

This SOW describes services requested of Applied Research and Associates, Inc. (ARA), as a commercial provider of cone penetrometer equipment and services, to provide routine inspection and minimum preventive maintenance on the Hanford CP Platform (CPP) during Fiscal Year 1999. This SOW specifically pertains to the maintenance of the CPP and associated support equipment and is limited in scope to routine preventive maintenance and identification of any deficiencies. ARA is the original manufacturer of the CPP and will conduct this work following the vendor-prepared maintenance schedule.

Genome-scan analysis for genetic mapping of quantitative trait loci underlying birth weight and onset of puberty in doe kids (Capra hircus).

PubMed

Esmailizadeh, A K

2014-12-01

The objective of this study was to locate quantitative trait loci (QTL) causing variation in birth weight and age of puberty of doe kids in a population of Rayini cashmere goats. Four hundred and thirty kids from five half-sib families were genotyped for 116 microsatellite markers located on the caprine autosomes. The traits recorded were birth weight of the male and female kids, body weight at puberty, average daily gain from birth to age of puberty and age at puberty of the doe kids. QTL analysis was conducted using the least squares interval mapping approach. Linkage analysis indicated significant QTL for birth weight on Capra hircus chromosomes (CHI) 4, 5, 6, 18 and 21. Five QTL located on CHI 5, 14 and 29 were associated with age at puberty. Across-family analysis revealed evidence for overlapping QTL affecting birth weight (78 cM), body weight at puberty (72 cM), average daily gain from birth to age of puberty (72 cM) and age at puberty (76 cM) on CHI 5 and overlapping QTL controlling body weight at puberty and age at puberty on CHI 14 at 18-19 cM. The proportion of the phenotypic variance explained by the detected QTL ranged between 7.9% and 14.4%. Confirming some of the previously reported results for birth weight and growth QTL in goats, this study identified more QTL for these traits and is the first report of QTL for onset of puberty in doe kids. © 2014 Stichting International Foundation for Animal Genetics.

Dynamic NMDAR-mediated properties of place cells during the object place memory task.

PubMed

Faust, Thomas W; Robbiati, Sergio; Huerta, Tomás S; Huerta, Patricio T

2013-01-01

N-methyl-D-aspartate receptors (NMDAR) in the hippocampus participate in encoding and recalling the location of objects in the environment, but the ensemble mechanisms by which NMDARs mediate these processes have not been completely elucidated. To address this issue, we examined the firing patterns of place cells in the dorsal CA1 area of the hippocampus of mice (n = 7) that performed an object place memory (OPM) task, consisting of familiarization (T1), sample (T2), and choice (T3) trials, after systemic injection of 3-[(±)2-carboxypiperazin-4yl]propyl-1-phosphate (CPP), a specific NMDAR antagonist. Place cell properties under CPP (CPP-PCs) were compared to those after control saline injection (SAL-PCs) in the same mice. We analyzed place cells across the OPM task to determine whether they signaled the introduction or movement of objects by NMDAR-mediated changes of their spatial coding. On T2, when two objects were first introduced to a familiar chamber, CPP-PCs and SAL-PCs showed stable, vanishing or moving place fields in addition to changes in spatial information (SI). These metrics were comparable between groups. Remarkably, previously inactive CPP-PCs (with place fields emerging de novo on T2) had significantly weaker SI increases than SAL-PCs. On T3, when one object was moved, CPP-PCs showed reduced center-of-mass (COM) shift of their place fields. Indeed, a subset of SAL-PCs with large COM shifts (>7 cm) was largely absent in the CPP condition. Notably, for SAL-PCs that exhibited COM shifts, those initially close to the moving object followed the trajectory of the object, whereas those far from the object did the opposite. Our results strongly suggest that the SI changes and COM shifts of place fields that occur during the OPM task reflect key dynamic properties that are mediated by NMDARs and might be responsible for binding object identity with location.

D1- and D2-like dopamine receptors in the CA1 region of the hippocampus are involved in the acquisition and reinstatement of morphine-induced conditioned place preference.

PubMed

Assar, Nasim; Mahmoudi, Dorna; Farhoudian, Ali; Farhadi, Mohammad Hasan; Fatahi, Zahra; Haghparast, Abbas

2016-10-01

The hippocampus plays a vital role in processing contextual memories and reward related learning tasks, such as conditioned place preference (CPP). Among the neurotransmitters in the hippocampus, dopamine is deeply involved in reward-related processes. This study assessed the role of D1- and D2-like dopamine receptors within the CA1 region of the hippocampus in the acquisition and reinstatement of morphine-CPP. To investigate the role of D1 and D2 receptors in morphine acquisition, the animals received different doses of D1- and/or D2-like dopamine receptor antagonists (SCH23390 and sulpiride, respectively) into the CA1, 5min before the administration of morphine (5mg/kg, subcutaneously) during a 3-days conditioning phase. To evaluate the involvement of these receptors in morphine reinstatement, the animals received different doses of SCH23390 or sulpiride (after extinction period) 5min before the administration of a low dose of morphine (1mg/kg) in order to reinstate the extinguished morphine-CPP. Conditioning scores were recorded by Ethovision software. The results of this study showed that the administration of SCH23390 or sulpiride, significantly decreased the acquisition of morphine-CPP. Besides, the injection of these antagonists before the administration of a priming dose of morphine, following the extinction period, decreased the reinstatement of morphine-CPP in sacrificed rats. However, the effect of sulpiride on the acquisition and reinstatement of morphine-CPP was more significant than that of SCH23390. These findings suggested that D1- and D2-like dopamine receptors in the CA1 are involved in the acquisition and reinstatement of morphine-CPP, and antagonism of these receptors can reduce the rewarding properties of morphine. Copyright © 2016 Elsevier B.V. All rights reserved.

Randomized clinical trial of the effect of NovaMin and CPP-ACPF in combination with dental bleaching.

PubMed

Alexandrino, Larissa Dias; Alencar, Cristiane de Melo; Silveira, Ana Daniela Silva da; Alves, Eliane Bemerguy; Silva, Cecy Martins

2017-01-01

This randomized, controlled, double-blind clinical study evaluated the effect of calcium sodium phosphosilicate (NovaMin) and casein phosphopeptide-amorphous calcium phosphate with fluoride (CPP-ACPF) on the prevention of post-operative sensitivity and on the effects of clinical bleaching treatment. Sixty volunteers were selected according to inclusion and exclusion criteria and were randomly assigned into three groups (n=20): CG (control group) patients, who were treated with 35% hydrogen peroxide; NOVAG (NovaMin group) patients, who were treated with 35% hydrogen peroxide followed by the application of NovaMin; and CPPG (CPP group) patients, who were treated with 35% hydrogen peroxide followed by the application of CPP-ACPF. Both bioactive agents were applied for five minutes. An evaporative stimulus associated with a modified visual scale was used to analyze sensitivity 24 hours after each bleaching session. The color evaluation was performed on the maxillary central incisors using a spectrophotometer. Associations between the intervention group, bleaching session, and reported sensitivity were tested using Chi-square partitioning. Color change values (ΔE) were analyzed using analysis of variance (ANOVA). The significance level used for both tests was 5%. In the intragroup assessment, the Friedman test showed that only the CPP-ACPF group showed no statistically significant difference (p<0.05) between baseline and first bleaching session. In the intergroup assessment, the Kruskal-Wallis test showed that the CPPG had less postoperative sensitivity after the first session, when compared to the other groups (p<0.05). Color change analysis (ΔE) showed a significant difference between the means obtained in the different bleaching sessions in all groups (p<0.05). This study showed that the combination of CPP-ACPF with 35% hydrogen peroxide significantly reduced post-operative sensitivity in the first session, compared with the other evaluated treatments. The association of CPP-ACPF and NovaMin did not affect the color change induced by tooth bleaching.

Current advancements in the diagnosis and treatment of chronic pelvic pain.

PubMed

Morrissey, Darlene; Ginzburg, Natasha; Whitmore, Kristene

2014-07-01

The diagnosis and treatment of chronic pelvic pain (CPP) have moved away from targeting a specific organ to multifactorial and multidisciplinary individualized approach to treatment strategies. The purpose of this article is to review the current advancements in diagnosis and treatment of CPP. Recognition that response to current treatment approach to CPP syndrome is variable; organizations such as the European Association of Urology, American Urologic Association, International Continence Society, International Association for the Study of Pain, and others have integrated the most current evidence and management strategies from multiple specialties (urology, gynecology, pain medicine, gastroenterology, colorectal surgery, neurology, physiotherapy, and psychology). The 1 World Congress on Pelvic Pain met in 2013 to further collaborate on diagnosis and management of CPP. A multimodal clinical phenotype system has also been implemented to help understand cause and guide therapy. New classification systems allow for overlap of mechanisms between conditions and a multidisciplinary treatment approach.

Influences on the onset and tempo of puberty in human beings and implications for adolescent psychological development.

PubMed

Lee, Yvonne; Styne, Dennis

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". Historical records reveal a secular trend toward earlier onset of puberty in both males and females, often attributed to improvements in nutrition and health status. The trend stabilized during the mid 20th century in many countries, but recent studies describe a recurrence of a decrease in age of pubertal onset. There appears to be an associated change in pubertal tempo in girls, such that girls who enter puberty earlier have a longer duration of puberty. Puberty is influenced by genetic factors but since these effects cannot change dramatically over the past century, environmental effects, including endocrine disrupting chemicals (EDCs), and perinatal conditions offer alternative etiologies. Observations that the secular trends in puberty in girls parallel the obesity epidemic provide another plausible explanation. Early puberty has implications for poor behavioral and psychosocial outcomes as well as health later in life. Irrespective of the underlying cause of the ongoing trend toward early puberty, experts in the field have debated whether these trends should lead clinicians to reconsider a lower age of normal puberty, or whether such a new definition will mask a pathologic etiology. Copyright © 2013 Elsevier Inc. All rights reserved.

[Wavelet packet extraction and entropy analysis of telemetry EEG from the prelimbic cortex of medial prefrontal cortex in morphine-induced CPP rats].

PubMed

Bai, Yu; Bai, Jia-Ming; Li, Jing; Li, Min; Yu, Ran; Pan, Qun-Wan

2014-12-25

The purpose of the present study is to analyze the relationship between the telemetry electroencephalogram (EEG) changes of the prelimbic (PL) cortex and the drug-seeking behavior of morphine-induced conditioned place preference (CPP) rats by using the wavelet packet extraction and entropy measurement. The recording electrode was stereotactically implanted into the PL cortex of rats. The animals were then divided randomly into operation-only control and morphine-induced CPP groups, respectively. A CPP video system in combination with an EEG wireless telemetry device was used for recording EEG of PL cortex when the rats shuttled between black-white or white-black chambers. The telemetry recorded EEGs were analyzed by wavelet packet extraction, Welch power spectrum estimate, normalized amplitude and Shannon entropy algorithm. The results showed that, compared with operation-only control group, the left PL cortex's EEG of morphine-induced CPP group during black-white chamber shuttling exhibited the following changes: (1) the amplitude of average EEG for each frequency bands extracted by wavelet packet was reduced; (2) the Welch power intensity was increased significantly in 10-50 Hz EEG band (P < 0.01 or P < 0.05); (3) Shannon entropy was increased in β, γ₁, and γ₂waves of the EEG (P < 0.01 or P < 0.05); and (4) the average information entropy was reduced (P < 0.01). The results suggest that above mentioned EEG changes in morphine-induced CPP group rat may be related to animals' drug-seeking motivation and behavior launching.

Enhancement of biocompatibility of 316LVM stainless steel by cyclic potentiodynamic passivation.

PubMed

Shahryari, Arash; Omanovic, Sasha; Szpunar, Jerzy A

2009-06-15

Passivation of stainless steel implants is a common procedure used to increase their biocompatibility. The results presented in this work demonstrate that the electrochemical cyclic potentiodynamic polarization (CPP) of a biomedical grade 316LVM stainless steel surface is a very efficient passivation method that can be used to significantly improve the material's general corrosion resistance and thus its biocompatibility. The influence of a range of experimental parameters on the passivation/corrosion protection efficiency is discussed. The passive film formed on a 316LVM surface by using the CPP method offers a significantly higher general corrosion resistance than the naturally grown passive film. The corresponding relative corrosion protection efficiency measured in saline during a 2-month period was 97% +/- 1%, which demonstrates a very high stability of the CPP-formed passive film. Its high corrosion protection efficiency was confirmed also at temperatures and chloride concentrations well above normal physiological levels. It was also shown that the CPP is a significantly more effective passivation method than some other surface-treatment methods commonly used to passivate biomedical grade stainless steels. In addition, the CPP-passivated 316LVM surface showed an enhanced biocompatibility in terms of preosteoblast (MC3T3) cells attachment. An increased thickness of the CPP-formed passive film and its enrichment with Cr(VI) and oxygen was determined to be the origin of the material's increased general corrosion resistance, whereas the increased surface roughness and surface (Volta) potential were suggested to be the origin of the enhanced preosteoblast cells attachment. Copyright 2008 Wiley Periodicals, Inc.

An in vitro study on the retentive strength of orthodontic bands cemented with CPP-ACP-containing GIC

NASA Astrophysics Data System (ADS)

Heravi, Farzin; Bagheri, Hossein; Rangrazi, Abdolrasoul; Mojtaba Zebarjad, Seyed

2016-12-01

Caries and white spot lesions around orthodontic bands are well known occurrences in fixed orthodontic treatment. There are several methods to overcome these problems. One of these includes modification of the band cement with remineralizing agents such as casein phosphopeptide-amorphous calcium phosphate (CPP-ACP). However, it should be evaluated that the cement modification has no significant negative effects on the retentive strength of the cemented orthodontic bands. In a continuation of our previous studies on the effects of the addition of CPP-ACP on the mechanical properties of luting and lining glass ionomer cement (GIC), this study aimed to investigate the retentive strength of orthodontic bands cemented with CPP-ACP containing GIC. Sixty extracted human pre molars teeth were embedded in acrylic resin and randomly divided into two groups of 30 specimens. In group 1, bands were cemented to the tooth with a GIC. In group 2, CPP-ACP (1.56% w/w) was added to the GIC before cementation. The retentive strength of each groups was determined with a universal testing machine. Further, the amount of cement remaining on the tooth surface was evaluated under a stereomicroscope, and the adhesive remnant index (ARI) score was determined. Results of this study showed that there were no significant differences between the groups in retentive strength and ARI score. In conclusion, modification of GIC with 1.56% w/w CPP-ACP had no negative effects on the retentive strength of the bands so can be used during fixed orthodontic treatment.

The effect of CPP-ACP on enamel wear under severe erosive conditions.

PubMed

Ranjitkar, Sarbin; Kaidonis, John A; Richards, Lindsay C; Townsend, Grant C

2009-06-01

In addition to its role as a remineralizing agent in preventing dental caries, recent evidence has shown that casein phosphopeptide-amorphous calcium phosphate (CPP-ACP) can protect teeth against erosion. The aim of this study was to determine whether CPP-ACP could reduce enamel wear rates under severe erosive conditions simulating heavy attrition and gastric regurgitation. Enamel specimens were subjected to 10,000 wear cycles at a load of 100 N and pH 1.2 in a tooth wear machine. The machine was stopped every 2 min (160 cycles), and CPP-ACP in the form of a paste was applied for 5 min in experimental group 1. A paste with the same formulation but without CPP-ACP was applied in experimental group 2. No paste was applied in the control group. A linear mixed model analysis indicated that the mean wear rates in experimental group 1 (0.44+/-0.05 mm(3) per 1000 cycles) and in experimental group 2 (0.63+/-0.06 mm(3) per 1000 cycles) were significantly lower than that in the control group (0.92+/-0.11 mm(3) per 1000 cycles) (p<0.05). The mean wear rate in experimental group 1 was also lower than that in experimental group 2 (p<0.05). Wear facets in experimental groups 1 and 2 were noted to be smoother and more polished than those in the control group. Both remineralizing and lubricating properties of the paste containing CPP-ACP appear to contribute to wear reduction in enamel. These findings may lead to new strategies for the clinical management of tooth wear.

Cementitious porous pavement in stormwater quality control: pH and alkalinity elevation.

PubMed

Kuang, Xuheng; Sansalone, John

2011-01-01

A certain level of alkalinity acts as a buffer and maintains the pH value in a stable range in water bodies. With rapid urban development, more and more acidic pollutants flow to watersheds with runoff and drop alkalinity to a very low level and ultimately degrade the water environment. Cementitious porous pavement is an effective tool for stormwater acidic neutralization. When stormwater infiltrates cement porous pavement (CPP) materials, alkalinity and pH will be elevated due to the basic characteristics of cement concrete. The elevated alkalinity will neutralize acids in water bodies and maintain the pH in a stable level as a buffer. It is expected that CPP materials still have a certain capability of alkalinity elevation after years of service, which is important for CPP as an effective tool for stormwater management. However, few previous studies have reported on how CPP structures would elevate runoff alkalinity and pH after being exposed to rainfall-runoff for years. In this study, three groups of CPP specimens, all exposed to rainfall-runoff for 3 years, were used to test the pH and alkalinity elevation properties. It was found that runoff pH values were elevated from 7.4 to the range of 7.8-8.6 after infiltrating through the uncoated specimens, and from 7.4 to 8.5-10.7 after infiltrating through aluminum-coated specimens. Runoff alkalinity elevation efficiencies are 11.5-14.5% for uncoated specimens and 42.2% for coated specimens. The study shows that CPP is an effective passive unit operation for stormwater acid neutralization in our built environment.

Musculoskeletal Dysfunctions in Patients With Chronic Pelvic Pain: A Preliminary Descriptive Survey.

PubMed

Mieritz, Rune Mygind; Thorhauge, Kirsten; Forman, Axel; Mieritz, Hanne Beck; Hartvigsen, Jan; Christensen, Henrik Wulff

The purpose of this study was to determine the prevalence of musculoskeletal dysfunctions based on a standardized clinical examination of patients with chronic pelvic pain (CPP) who were referred to a specialized tertiary care center for laparoscopic examination. In addition, we stratified levels of self-reported pelvic pain, self-rated health, education, and work status based on musculoskeletal dysfunction status. This study used a cross-sectional design to determine the prevalence of musculoskeletal dysfunctions in women with CPP who were referred to a tertiary care center specializing in care of women with CPP. The women completed a questionnaire and underwent a blinded systematic objective clinical examination of the musculoskeletal system by a doctor of chiropractic who then categorized the patients as having or not having musculoskeletal dysfunction. Ninety-four patients returned the questionnaire, completed the clinical examination, and fulfilled the inclusion criteria. More than half of the referred patients with CPP (48 out of 94) had musculoskeletal dysfunctions in the lumbar/pelvic region. No statistically significant differences were found between the groups with respect to self-rated health, education, work status, and pain level. Pain location was significantly different after Bonferroni correction in 1 out of the 36 aspects. In this sample of CPP patients, 51% were categorized as having a musculoskeletal dysfunction. Overall, CPP patients were similar with respect to certain characteristics, such as age, body mass index, and pain level, regardless of their classification; however, patients with musculoskeletal dysfunction tended to report more pain in the front and back of the lower limbs. Copyright © 2016. Published by Elsevier Inc.

Rapamycin prevents drug seeking via disrupting reconsolidation of reward memory in rats.

PubMed

Lin, Jue; Liu, Lingqi; Wen, Quan; Zheng, Chunming; Gao, Yang; Peng, Shuxian; Tan, Yalun; Li, Yanqin

2014-01-01

The maladaptive drug memory developed between the drug-rewarding effect and environmental cues contributes to difficulty in preventing drug relapse. Established reward memories can be disrupted by pharmacologic interventions following their reactivation. Rapamycin, an inhibitor of mammalian target of rapamycin (mTOR) kinase, has been proved to be involved in various memory consolidation. However, it is less well characterized in drug memory reconsolidation. Using a conditioned place preference (CPP) procedure, we examined the effects of systemically administered rapamycin on reconsolidation of drug memory in rats. We found that systemically administered rapamycin (0.1 or 10 mg/kg, i.p.) after re-exposure to drug-paired environment, dose dependently decreased the expression of CPP 1 d later, and the effect lasted for up to 14 d and could not be reversed by a priming injection of morphine. The effect of rapamycin on morphine-associated memory was specific to drug-paired context, and rapamycin had no effect on subsequent CPP expression when rats were exposed to saline-paired context or homecage. These results indicated that systemic administration of rapamycin after memory reactivation can persistently inhibit the drug seeking behaviour via disruption of morphine memory reconsolidation in rats. Additionally, the effect of rapamycin on memory reconsolidation was reproduced in cocaine CPP and alcohol CPP. Furthermore, rapamycin did not induce conditioned place aversion and had no effect on locomotor activity and anxiety behaviour. These findings suggest that rapamycin could erase the acquired drug CPP in rats, and that mTOR activity plays an important role in drug reconsolidation and is required for drug relapse.

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTHWEST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-51-1390. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12124. Unknown Photographer, 9/21/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING NUMBER 200062700098105071. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105071. ALTERNATE ID NUMBER 4272-14-108. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP601) LOOKING EAST. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW OF MAIN PROCESSING BUILDING (CPP-601) LOOKING EAST. INL PHOTO NUMBER NRTS-51-1547. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates.

PubMed

Stephens, Shannon B Z; Wallen, Kim

2013-07-01

This article is part of a Special Issue "Puberty and Adolescence". Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior. Copyright © 2013 Elsevier Inc. All rights reserved.

Sol gel-derived hydroxyapatite films over porous calcium polyphosphate substrates for improved tissue engineering of osteochondral-like constructs.

PubMed

Lee, Whitaik David; Gawri, Rahul; Pilliar, Robert M; Stanford, William L; Kandel, Rita A

2017-10-15

Integration of in vitro-formed cartilage on a suitable substrate to form tissue-engineered implants for osteochondral defect repair is a considerable challenge. In healthy cartilage, a zone of calcified cartilage (ZCC) acts as an intermediary for mechanical force transfer from soft to hard tissue, as well as an effective interlocking structure to better resist interfacial shear forces. We have developed biphasic constructs that consist of scaffold-free cartilage tissue grown in vitro on, and interdigitated with, porous calcium polyphosphate (CPP) substrates. However, as CPP degrades, it releases inorganic polyphosphates (polyP) that can inhibit local mineralization, thereby preventing the formation of a ZCC at the interface. Thus, we hypothesize that coating CPP substrate with a layer of hydroxyapatite (HA) might prevent or limit this polyP release. To investigate this we tested both inorganic or organic sol-gel processing methods, asa barrier coating on CPP substrate to inhibit polyP release. Both types of coating supported the formation of ZCC in direct contact with the substrate, however the ZCC appeared more continuous in the tissue formed on the organic HA sol gel coated CPP. Tissues formed on coated substrates accumulated comparable quantities of extracellular matrix and mineral, but tissues formed on organic sol-gel (OSG)-coated substrates accumulated less polyP than tissues formed on inorganic sol-gel (ISG)-coated substrates. Constructs formed with OSG-coated CPP substrates had greater interfacial shear strength than those formed with ISG-coated and non-coated substrates. These results suggest that the OSG coating method can modify the location and distribution of ZCC and can be used to improve the mechanical integrity of tissue-engineered constructs formed on porous CPP substrates. Articular cartilage interfaces with bone through a zone of calcified cartilage. This study describes a method to generate an "osteochondral-like" implant that mimics this organization using isolated deep zone cartilage cells and a sol-gel hydroxyapatite coated bone substitute material composed of calcium polyphosphate (CPP). Developing a layer of calcified cartilage at the interface should contribute to enhancing the success of this "osteochondral-like" construct following implantation to repair cartilage defects. Copyright © 2017 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Effect of Weight Loss on Puberty Onset in Overweight Children.

PubMed

Reinehr, Thomas; Bosse, Christina; Lass, Nina; Rothermel, Juliane; Knop, Caroline; Roth, Christian Ludwig

2017-05-01

To assess the impact of weight changes on the onset of puberty in overweight children. We evaluated the timing of puberty onset in 160 prepubertal overweight children (aged 11.2 ± 1.0 years) depending on the changes of their weight status in a 1-year lifestyle intervention. We determined body mass index (BMI), pubertal stage, luteinizing hormone (LH), follicle-stimulating hormone, insulin-like growth factor (IGF)-1, insulin-like growth factor binding protein-3, insulin resistance index homeostatic model assessment, and serum gonadotropins at baseline and 1 year later. Puberty onset during the 1-year follow-up was significantly (P = .014) more frequent in girls without BMI-SDS reduction (75.0%) compared with girls with BMI-SDS reduction (45.7%). The start of puberty was significantly (P = .024) more frequent in boys with BMI-SDS reduction (76.9%) compared with boys without BMI-SDS reduction (53.6%). In logistic regression analyses adjusted for baseline age and BMI-SDS, BMI-SDS reduction was associated with a decreased likelihood for puberty onset in girls (OR 0.24; 95% CI 0.07-0.85) and an increased likelihood in boys (OR 3.77; 95% CI 1.34-10.52). Central onset of puberty was confirmed by an increase of LH concentration and LH/follicle-stimulating hormone ratio in both boys and girls. Homeostatic model assessment, IGF-1, and IGF-1/insulin-like growth factor binding protein-3 ratio as marker for free IGF-1 at baseline or their changes were not associated with the onset of puberty. BMI-SDS reduction in overweight children was associated with earlier gonadotropin-dependent onset of puberty in boys and later onset of puberty in girls, suggesting earlier puberty in obese girls and later puberty in obese boys. We found no evidence that insulin resistance or IGF-1 have an impact on the start of puberty in obese children. ClinicalTrials.gov: NCT00435734. Copyright © 2017 Elsevier Inc. All rights reserved.

Parenting a Precocious Preschooler: Breaking the Silence

ERIC Educational Resources Information Center

Fish, Leigh Ann

2016-01-01

Precocity in the very young should be a valid topic of discussion in parental and educational circles, yet too frequently those conversations are slow to occur or are absent altogether. Many parents and educators remain silent about raising and nurturing precocious preschoolers, and author Leigh Ann Fish believe that the silence is due to a lack…

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP627). INL DRAWING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105631. ALTERNATE ID NUMBER 4272-814-134. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP603) LOOKING EAST SHOWING ASBESTOS ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION VIEW FUEL STORAGE BUILDING (CPP-603) LOOKING EAST SHOWING ASBESTOS SIDING. INL PHOTO NUMBER NRTS-51-1543. Unknown Photographer, 2/28/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP601) LOOKING NORTH. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTH. INL PHOTO NUMBER NRTS-51-1387. Unknown Photographer, 1/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH ELEVATION OF HOT PILOT PLANT (CPP640) LOOKING NORTH. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH ELEVATION OF HOT PILOT PLANT (CPP-640) LOOKING NORTH. INL PHOTO NUMBER HD-22-3-1. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP603) LOOKING NORTHWEST. ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO SHOWING FUEL STORAGE BUILDING (CPP-603) LOOKING NORTHWEST. INL PHOTO NUMBER NRTS-50-895. Unknown Photographer, 10/30/1950 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP603). INL DRAWING NUMBER ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

BUILDING PLANS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103029. ALTERNATE ID NUMBER 542-31-B-21. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627). INL PHOTO ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627). INL PHOTO NUMBER NRTS-54-12573. R.G. Larsen, Photographer, 10/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627) SHOWING INITIAL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING INITIAL EXCAVATION. INL PHOTO NUMBER NRTS-54-10703. Unknown Photographer, 5/21/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH ELEVATION OF MAIN PROCESSING BUILDING (CPP601) LOOKING NORTH. INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH ELEVATION OF MAIN PROCESSING BUILDING (CPP-601) LOOKING NORTH. INL PHOTO NUMBER HD-22-5-3. Mike Crane, Photographer, 11/1998 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Physical Therapy Treatment of Pelvic Pain.

PubMed

Bradley, Michelle H; Rawlins, Ashley; Brinker, C Anna

2017-08-01

Physical therapists offer a valuable service in the treatment of chronic pelvic pain (CPP). Physical therapists are trained in functional restoration of the whole body. The physical therapist is in the unique position to assess and treat CPP in restoration of transitional movement ease and tolerance for improved functional control with the ultimate goal of wellness. It is imperative that pelvic floor muscle overactivity, underactivity, or a combination there of is accurately assessed and treated to avoid exacerbation of symptoms. The physical therapist has treatment options to restore the function with education in independent management of CPP. Copyright © 2017 Elsevier Inc. All rights reserved.

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

Not Available

The 21st Century Power Partnership's program in Mexico (21CPP Mexico) is one initiative of the Clean Energy Ministerial, carried out in cooperation with government and local stakeholders, drawing upon an international community of power system expertise. The overall goal of this program is to support Mexico's power system transformation by accelerating the transition to a reliable, financially robust, and low-carbon system. 21CPP Mexico activities focus on achieving positive outcomes for all participants, especially addressing critical questions and challenges facing policymakers, regulators, and system operators. In support of this goal, 21CPP Mexico taps into deep networks of expertise and professional connections.

A possible link between dysmenorrhoea and the development of chronic pelvic pain.

PubMed

Hardi, Gemma; Evans, Susan; Craigie, Meredith

2014-12-01

Anecdotally, severe dysmenorrhoea can pre-date the development of chronic pelvic pain (CPP). This study describes the timeline for the transition from dysmenorrhoea to CPP in a cohort of new patients attending a private gynaecology clinic. In 16.4% of cases, transition occurred within one year, and within 12 years in over 50%. Our study suggests clinicians need to observe women with severe dysmenorrhoea for signs of chronic pain. Further research is needed into the transition from dysmenorrhoea to CPP, and effective early interventions. © 2014 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

CPP-115, a Potent γ-Aminobutyric Acid Aminotransferase Inactivator for the Treatment of Cocaine Addiction

PubMed Central

Pan, Yue; Gerasimov, Madina R.; Kvist, Trine; Wellendorph, Petrine; Madsen, Karsten K.; Pera, Elena; Lee, Hyunbeom; Schousboe, Arne; Chebib, Mary; Bräuner-Osborne, Hans; Craft, Cheryl M.; Brodie, Jonathan D.; Schiffer, Wynne K.; Dewey, Stephen L.; Miller, Steven R.; Silverman, Richard B.

2011-01-01

Vigabatrin, a GABA aminotransferase (GABA-AT) inactivator, is used to treat infantile spasms and refractory complex partial seizures and is in clinical trials to treat addiction. We evaluated a novel GABA-AT inactivator (CPP-115) and observed that it does not exhibit other GABAergic or off-target activities and is rapidly and completely orally absorbed and eliminated. Using in vivo microdialysis techniques in freely moving rats and micro-PET imaging techniques, CPP-115 produced similar inhibition of cocaine-induced increases in extracellular dopamine and in synaptic dopamine in the nucleus accumbens at 1/300–1/600th the dose of vigabatrin. It also blocks expression of cocaine-induced conditioned place preference at a dose 1/300th that of vigabatrin. Electroretinographic (ERG) responses in rats treated with CPP-115, at doses 20–40 times higher than those needed to treat addiction in rats, exhibited reductions in ERG responses, which were less than the reductions observed in rats treated with vigabatrin at the same dose needed to treat addiction in rats. In conclusion, CPP-115 can be administered at significantly lower doses than vigabatrin, which suggests a potential new treatment for addiction with a significantly reduced risk of visual field defects. PMID:22128851

Post-Retrieval Extinction Attenuates Cocaine Memories

PubMed Central

Sartor, Gregory C; Aston-Jones, Gary

2014-01-01

Recent studies have shown that post-retrieval extinction training attenuates fear and reward-related memories in both humans and rodents. This noninvasive, behavioral approach has the potential to be used in clinical settings to treat maladaptive memories that underlie several psychiatric disorders, including drug addiction. However, few studies to date have used a post-retrieval extinction approach to attenuate addiction-related memories. In the current study, we attempted to disrupt cocaine-related memories by using the post-retrieval extinction paradigm in male Sprague Dawley rats. Results revealed that starting extinction training 1 h after cocaine contextual memory was retrieved significantly attenuated cocaine-primed reinstatement of conditioned place preference (CPP) and relapse of cocaine CPP (drug-free and cocaine-primed) following 30 days of abstinence. However, animals that did not retrieve the contextual cocaine memory before extinction training, or animals that began extinction training 24 h after retrieval (outside of the reconsolidation window), demonstrated normal cocaine CPP. Conversely, animals that received additional CPP conditioning, rather than extinction training, 1 h after reactivation of cocaine memory showed enhanced cocaine CPP compared with animals that did not reactivate the cocaine memory before conditioning. These results reveal that a behavioral manipulation that takes advantage of reconsolidation and extinction of drug memories may be useful in decreasing preference for, and abuse of, cocaine. PMID:24257156

Increased cellular uptake of peptide-modified PEGylated gold nanoparticles.

PubMed

He, Bo; Yang, Dan; Qin, Mengmeng; Zhang, Yuan; He, Bing; Dai, Wenbing; Wang, Xueqing; Zhang, Qiang; Zhang, Hua; Yin, Changcheng

2017-12-09

Gold nanoparticles are promising drug delivery vehicles for nucleic acids, small molecules, and proteins, allowing various modifications on the particle surface. However, the instability and low bioavailability of gold nanoparticles compromise their clinical application. Here, we functionalized gold nanoparticles with CPP fragments (CALNNPFVYLI, CALRRRRRRRR) through sulfhydryl PEG to increase their stability and bioavailability. The resulting gold nanoparticles were characterized with transmission electron microscopy (TEM), dynamic light scattering (DLS), UV-visible spectrometry and X-ray photoelectron spectroscopy (XPS), and the stability in biological solutions was evaluated. Comparing to PEGylated gold nanoparticles, CPP (CALNNPFVYLI, CALRRRRRRRR)-modified gold nanoparticles showed 46 folds increase in cellular uptake in A549 and B16 cell lines, as evidenced by the inductively coupled plasma atomic emission spectroscopy (ICP-AES). The interactions between gold nanoparticles and liposomes indicated CPP-modified gold nanoparticles bind to cell membrane more effectively than PEGylated gold nanoparticles. Surface plasmon resonance (SPR) was used to measure interactions between nanoparticles and the membrane. TEM and uptake inhibitor experiments indicated that the cellular entry of gold nanoparticles was mediated by clathrin and macropinocytosis. Other energy independent endocytosis pathways were also identified. Our work revealed a new strategy to modify gold nanoparticles with CPP and illustrated the cellular uptake pathway of CPP-modified gold nanoparticles. Copyright © 2017 Elsevier Inc. All rights reserved.

Agmatine attenuates nicotine induced conditioned place preference in mice through modulation of neuropeptide Y system.

PubMed

Kotagale, Nandkishor R; Walke, Sonali; Shelkar, Gajanan P; Kokare, Dadasaheb M; Umekar, Milind J; Taksande, Brijesh G

2014-04-01

The purpose of the present study was to examine the effect of agmatine on nicotine induced conditioned place preference (CPP) in male albino mice. Intra-peritoneal (ip) administration of nicotine (1mg/kg) significantly increased time spent in drug-paired compartment. Agmatine (20 and 40 mg/kg, ip) co-administered with nicotine during the 6 days conditioning sessions completely abolished the acquisition of nicotine-induced CPP in mice. Concomitant administration of neuropeptide Y (NPY) (1 pg/mouse, icv) or [Leu(31), Pro(34)]-NPY (0.1 pg/mouse, icv), selective NPY Y1 receptor agonist potentiated the inhibitory effect of agmatine (10 mg/kg, ip) on nicotine CPP. Conversely, pretreatment with NPY Y1 receptor antagonist, BIBP3226 (0.01 ng/mouse, icv) blocked the effect of agmatine (20 mg/kg, ip) on nicotine induced CPP. In immunohistochemical study, nicotine decreased NPY-immunoreactivity in nucleus accumbens shell (AcbSh), bed nucleus of stria terminalis, lateral part (BNSTl), arcuate nucleus (ARC) and paraventricular nucleus (PVN). Conversely, administration of agmatine prior to the nicotine significantly reversed the effect of nicotine on NPY-immunoreactivity in the above brain nuclei. This data indicate that agmatine attenuate nicotine induced CPP via modulation of NPYergic neurotransmission in brain. Copyright © 2014 Elsevier B.V. All rights reserved.

Pubertal development and regulation

PubMed Central

Abreu, Ana Paula; Kaiser, Ursula B

2016-01-01

Puberty marks the end of childhood and is a period when individuals undergo physiological and psychological changes to achieve sexual maturation and fertility. The hypothalamic-pituitary-gonadal axis controls puberty and reproduction and is tightly regulated by a complex network of excitatory and inhibitory factors. This axis is active in the embryonic and early postnatal stages of life and is subsequently restrained during childhood, and its reactivation culminates in puberty initiation. The mechanisms underlying this reactivation are not completely known. The age of puberty onset varies between individuals and the timing of puberty initiation is associated with several health outcomes in adult life. In this Series paper, we discuss pubertal markers, epidemiological trends of puberty initiation over time, and the mechanisms whereby genetic, metabolic, and other factors control secretion of gonadotropin-releasing hormone to determine initiation of puberty. PMID:26852256

Environmental and social influences on neuroendocrine puberty and behavior in macaques and other nonhuman primates

PubMed Central

Stephens, Shannon B. Z.; Wallen, Kim

2013-01-01

Puberty is the developmental period when the hypothalamic-pituitary-gonadal (HPG) axis is activated, following a juvenile quiescent period, and reproductive capacity matures. Although pubertal events occur in a consistent sequence, there is considerable variation between individuals in the onset and timing of pubertal events, with puberty onset occurring earlier in girls than in boys. Evidence in humans demonstrates that social and environmental context influences the timing of puberty onset and may account for some of the observed variation. This review analyzes the nonhuman primate literature, focusing primarily on rhesus macaques (Macaca mulatta), to examine the social and environmental influences on puberty onset, how these factors influence puberty in males and females, and to review the relationship between puberty onset of adult neuroendocrine function and sexual behavior. Social and environmental factors influence the timing of puberty onset and pubertal events in nonhuman primates, as in humans, and the influences of these factors differ for males and females. In nonhuman primates, gonadal hormones are not required for sexual behavior, but modulate the frequency of occurrence of behavior, with social context influencing the relationship between gonadal hormones and sexual behavior. Thus, the onset of sexual behavior is independent of neuroendocrine changes at puberty; however, there are distinct behavioral changes that occur at puberty, which are modulated by social context. Puberty is possibly the developmental period when hormonal modulation of sexual behavior is organized, and thus, when social context interacts with hormonal state to strongly influence the expression of sexual behavior. PMID:23998667

Childhood family disruption and adult height: is there a mediating role of puberty?

PubMed Central

Sheppard, Paula; Garcia, Justin R.; Sear, Rebecca

2015-01-01

Background and objectives: Childhood family background is known to be associated with child growth and development, including the onset of puberty, but less is known about the influence of childhood family disruption on outcomes in later life. Given the associations between early family disruption and childhood development, we predicted that there may be long-term health-relevant consequences of childhood disruption. Methodology: Using data from a large US interview sample (n = 16 207), we test if death or divorce of parents, at different childhood periods, was associated with adult stature, and whether age at puberty mediated this relationship, for men and women. Results: Men: parental death and divorce during early childhood was associated with shorter adult height, and later puberty. Later puberty was associated with shorter adult height. Path analyses demonstrated that the relationship between parental divorce and height was completely mediated by age at puberty; although parental death was only partially mediated by age at puberty. Women: the father’s death during early childhood was associated with earlier puberty, which was in turn associated with shorter adult stature. The relationship between paternal death and height is entirely mediated by age at puberty; no evidence of a direct relationship between childhood family disruption and adult height. Conclusions: Early childhood familial disruption is associated with shorter height for men, and is partially mediated by later puberty. For women, the relationship between father’s death, and height was completely mediated by earlier puberty. These findings indicate that disruption during childhood can have long-reaching health repercussions, particularly for boys. PMID:26609061

For Parents: What to Expect When Your Child Goes through Puberty

MedlinePlus

... What are the first signs of puberty in boys and girls? The first sign of puberty in most girls ... development. The first sign of puberty in most boys is an increase in the size of ... Yes. In girls, breasts develop first. Then, hair starts growing in ...

MISCELLANEOUS ARCHITECTURAL DETAILS AND SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP627). ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS ARCHITECTURAL DETAILS AND SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105632. ALTERNATE ID NUMBER 4272-814-135. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

MISCELLANEOUS SECTIONS AND DETAILS OF FUEL STORAGE BUILDING (CPP603). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

MISCELLANEOUS SECTIONS AND DETAILS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103032. ALTERNATE ID NUMBER 542-31-B-24. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). PHOTO TAKEN LOOKING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-20-1. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SOUTH ELEVATION AND DETAILS OF MAIN PROCESSING BUILDING (CPP601). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SOUTH ELEVATION AND DETAILS OF MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-103082. ALTERNATE ID NUMBER 542-12-B-76. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

NORTH AND SOUTH SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP627). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

NORTH AND SOUTH SECTIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105068. ALTERNATE ID NUMBER 4272-14-105. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP627). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST AND WEST ELEVATIONS OF REMOTE ANALYTICAL FACILITY (CPP-627). INL DRAWING NUMBER 200-0627-00-098-105067. ALTERNATE ID NUMBER 4272-14-104. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

EAST AND WEST ELEVATIONS OF MAIN PROCESSING BUILDING (CPP601). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

EAST AND WEST ELEVATIONS OF MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-103081. ALTERNATE ID NUMBER 542-11-B-75. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

WEST ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING (CPP603). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATIONS AND SECTIONS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-063-61-299-103031. ALTERNATE ID NUMBER 542-31-B-23. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

SIDING AND ROOF DETAILS OF FUEL STORAGE BUILDING (CPP603). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

SIDING AND ROOF DETAILS OF FUEL STORAGE BUILDING (CPP-603). INL DRAWING NUMBER 200-0603-61-299-103033. ALTERNATE ID NUMBER 542-31-B-25. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP603) SHOWING CRANE ASSEMBLY ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

INTERIOR VIEW OF FUEL STORAGE BUILDING (CPP-603) SHOWING CRANE ASSEMBLY FOR TRANSFER PIT. INL PHOTO NUMBER NRTS-51-2404. Unknown Photographer, 5/31/1951 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP603). PHOTO TAKEN LOOKING ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

WEST ELEVATION OF FUEL STORAGE BUILDING (CPP-603). PHOTO TAKEN LOOKING NORTHEAST. INL PHOTO NUMBER HD-54-20-3. Mike Crane, Photographer, 8/2005 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

BUILDING DETAILS AND SECTIONS OF MAIN PROCESSING BUILDING (CPP601). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

BUILDING DETAILS AND SECTIONS OF MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-103080. ALTERNATE ID NUMBER 542-11-B-74. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

STRUCTURAL DETAILS AND SECTIONS OF MAIN PROCESSING BUILDING (CPP601). INL ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

STRUCTURAL DETAILS AND SECTIONS OF MAIN PROCESSING BUILDING (CPP-601). INL DRAWING NUMBER 200-0601-00-291-103079. ALTERNATE ID NUMBER 542-11-B-73. - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP627) SHOWING PLACEMENT ...

Library of Congress Historic Buildings Survey, Historic Engineering Record, Historic Landscapes Survey

CONSTRUCTION PROGRESS PHOTO OF REMOTE ANALYTICAL FACILITY (CPP-627) SHOWING PLACEMENT OF PIERS. INL PHOTO NUMBER NRTS-54-11716. Unknown Photographer, 8/20/1954 - Idaho National Engineering Laboratory, Idaho Chemical Processing Plant, Fuel Reprocessing Complex, Scoville, Butte County, ID

Effect of calcium pyrophosphate on microstructural evolution and in vitro biocompatibility of Ti-35Nb-7Zr composite by spark plasma sintering.

PubMed

Zhang, L; Tan, J; He, Z Y; Jiang, Y H

2018-09-01

β-type Ti-35Nb-7Zr alloy has attracted considerable attentions as a bone implant material. The alloy, however, has poor bioactivity, which difficult to form a strong osseointegration between the bone tissues. Combining Ti alloy with a bioactive and biodegradable ceramic has been of interest to researchers. But the large difference in physicochemical property of high-melting metal and ceramic elements would bring the manufacturing restriction. In this work, Ti-35Nb-7Zr-CPP composites were fabricated with mechanical alloy of Ti, Nb, Zr and Nano calcium pyrophosphate (CPP) powders mixture followed by spark plasma sintering (SPS) routes. The effect of CPP ceramic on microstructural evolution and in vitro biocompatibility were investigated. As the addition of CPP (10-30 wt%), ceramic elements spreading towards the matrix, the generated metal-ceramic bioactive phases CaTiO 3 are observed well consolidated with β-Ti matrix. With the CPP increasing, Ca and P atoms rapidly migrated to the β-Ti matrix to form granulated Ti 5 P 3 , which leads to the increasing porosity (10%-18%) in the composites. The results demonstrated that the favorable cell viability (the cell proliferation rates were higher than 100%) and growth inside the pores of the composites arise from the rough micro-porous surface and the release of bioactive metal-ceramic phase ions into the biological environment. The enhanced bioactivity and microstructural evolution behaviors of the Ti-35Nb-7Zr-CPP composites may provide a strategy for designing and fabricating multifunctional implants. Copyright © 2018 Elsevier B.V. All rights reserved.