Substance P regulates puberty onset and fertility in the female mouse

Puberty is a tightly regulated process that leads to reproductive capacity. Kiss1 neurons are crucial in this process by stimulating GnRH, yet how Kiss1 neurons are regulated remains unknown. Substance P (SP), an important neuropeptide in pain perception, induces gonadotropin release in adult mice in a kisspeptin-dependent manner. Here, we assessed whether SP, through binding to its receptor NK1R (neurokinin 1 receptor), participates in the timing of puberty onset and fertility in the mouse. We observed that 1) selective NK1R agonists induce gonadotropin release in prepubertal females; 2) the expression of Tac1 (encoding SP) and Tacr1 (NK1R) in the arcuate nucleus is maximal before puberty, suggesting increased SP tone; 3) repeated exposure to NK1R agonists prepubertally advances puberty onset; and 4) female Tac1-/- mice display delayed puberty; moreover, 5) SP deficiency leads to subfertility in females, showing fewer corpora lutea and antral follicles and leading to decreased litter size. Thus, our findings support a role for SP in the stimulation of gonadotropins before puberty, acting via Kiss1 neurons to stimulate GnRH release, and its involvement in the attainment of full reproductive capabilities in female mice. Copyright © 2015 by the Endocrine Society

Inhibitory effects of regorafenib, a multiple tyrosine kinase inhibitor, on corneal neovascularization

<b>AIM:</b>To evaluate the inhibitory effects of regorafenib (BAY 73-4506), a multikinase inhibitor, on corneal neovascularization (NV).<b>METHODS:</b>Thirty adult male Sprague-Dawley rats weighing 250-300 g, were used. Corneal NV was induced by NaOH in the left eyes of each rat. Following the establishment of alkali burn, the animals were randomized into five groups according to topical treatment. Group 1 (<i>n </i>= 6) received 0.9% NaCl, Group 2 (<i>n </i>= 6) received dimethyl sulfoxide, Group 3 (<i>n </i>= 6) received regorafenib 1 mg/mL, Group 4 (<i>n </i>=6) received bevacizumab 5 mg/mL and Group 5 (<i>n </i>= 6) received 0.1% dexamethasone phosphate. On the 7d, the corneal surface covered with neovascular vessels was measured on photographs as the percentage of the cornea’s total area using computer-imaging analysis. The corneas obtained from rats were semiquantitatively evaluated for caspase-3 and vascular endothelial growth factor by immunostaining.<b>RESULTS:</b>A statistically significant difference in the percent area of corneal NV was found among the groups (<i>P </i>&lt;0.001). Although the Group 5 had the smallest percent area of corneal NV, there was no difference among Groups 3, 4 and 5 (<i>P </i>&gt;0.005). There was a statistically significant difference among the groups in apoptotic cell density (<i>P </i>= 0.002). The staining intensity of vascular endothelial growth factor in the epithelial and endothelial layers of cornea was significantly different among the groups (<i>P </i>&lt;0.05). The staining intensity of epithelial and endothelial vascular endothelial growth factor was significantly weaker in Groups 3, 4 and 5 than in Groups 1 and 2.<b>CONCLUSION:</b> Topical administration of regorafenib 1 mg/mL is partly effective for preventing alkali-induced corneal NV in rats

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters

Effects of Age, Race, and Ethnicity on the Optic Nerve and Peripapillary Region Using Spectral-Domain OCT 3D Volume Scans

Purpose: To evaluate the effects of age, race, and ethnicity on the optic nerve and peripapillary retina using spectral-domain optical coherence tomography (SD-OCT) three-dimensional (3D) volume scans in normal subjects. Methods: This is a cross-sectional study performed at a single institution in Boston. All patients received retinal nerve fiber layer (RNFL) scans and an optic nerve 3D volume scan. The SD-OCT software calculated peripapillary RNFL thickness, retinal thickness (RT), and retinal volume (RV). Custom-designed software calculated neuroretinal rim minimum distance band (MDB) thickness and area. Results: There were 272 normal subjects, including 175 whites, 40 blacks, 40 Asians, and 17 Hispanics. Rates of age-related decline were 2.3%, 2.0%, 1.7%, 3.3%, and 4.3% per decade for RNFL, RT, RV, MDB neuroretinal rim thickness, and MDB area, respectively. The RNFL was most affected by racial and ethnic variations, with Asians having thicker global, superior, and inferior RNFL, Hispanics having thicker inferior RNFL, and blacks having thinner temporal RNFL, compared to whites. For MDB thickness and area, Asians had smaller nasal values and blacks had smaller temporal values. Peripapillary RT and RV parameters were not influenced by race and ethnicity. Conclusions: All of the parameters exhibited age-related declines. RNFL, MDB thickness, and MDB area demonstrated racial and ethnic variations, while peripapillary RT and RV did not. Translational Relevance: This study demonstrates that both normal aging and ethnicity affect several novel 3D OCT parameters used to diagnose and monitor glaucoma (i.e., RT, RV, and MDB), and this should be factored in when making clinical decisions based on these parameters

Characterization of the Role of NKA in the Control of Puberty Onset and Gonadotropin Release in the Female Mouse.

The tachykinin neurokinin B (NKB, Tac2) is critical for proper GnRH release in mammals, however, the role of the other tachykinins, such as substance P (SP) and neurokinin A (NKA) in reproduction, is still not well understood. In this study, we demonstrate that NKA controls the timing of puberty onset (similar to NKB and SP) and stimulates LH release in adulthood through NKB-independent (but kisspeptin-dependent) mechanisms in the presence of sex steroids. Furthermore, this is achieved, at least in part, through the autosynaptic activation of Tac1 neurons, which express NK2R (Tacr2), the receptor for NKA. Conversely, in the absence of sex steroids, as observed in ovariectomy, NKA inhibits LH through a mechanism that requires the presence of functional receptors for NKB and dynorphin (NK3R and KOR, respectively). Moreover, the ability of NKA to modulate LH secretion is absent in Kiss1KO mice, suggesting that its action occurs upstream of Kiss1 neurons. Overall, we demonstrate that NKA signaling is a critical component in the central control of reproduction, by contributing to the indirect regulation of kisspeptin release

Biomarkers of Nutrition for Development (BOND)—Iron Review

This is the fifth in the series of reviews developed as part of the Biomarkers of Nutrition for Development (BOND) program. The BOND Iron Expert Panel (I-EP) reviewed the extant knowledge regarding iron biology, public health implications, and the relative usefulness of currently available biomarkers of iron status from deficiency to overload. Approaches to assessing intake, including bioavailability, are also covered. The report also covers technical and laboratory considerations for the use of available biomarkers of iron status, and concludes with a description of research priorities along with a brief discussion of new biomarkers with potential for use across the spectrum of activities related to the study of iron in human health. The I-EP concluded that current iron biomarkers are reliable for accurately assessing many aspects of iron nutrition. However, a clear distinction is made between the relative strengths of biomarkers to assess hematological consequences of iron deficiency versus other putative functional outcomes, particularly the relationship between maternal and fetal iron status during pregnancy, birth outcomes, and infant cognitive, motor and emotional development. The I-EP also highlighted the importance of considering the confounding effects of inflammation and infection on the interpretation of iron biomarker results, as well as the impact of life stage. Finally, alternative approaches to the evaluation of the risk for nutritional iron overload at the population level are presented, because the currently designated upper limits for the biomarker generally employed (serum ferritin) may not differentiate between true iron overload and the effects of subclinical inflammation

The value of transvaginal ultrasonography in postmenopausal uterine bleeding

Objective: Endometrial carcinoma is the most common gynecologic malignancy and usually present with postmenopausal bleeding. For invastigating postmenopausal bleeding there is a trend to less invasiv procedures without compromising efficacy and safety. Transvaginal ultrasonography was suggested as a first-step procedure in evaluating women with postmenopausal bleeding. The aim of this study to evaluate the diagnostic accuracy of transvaginal ultrasonography and endometrial histopathology findings in patients presenting with postmenopausal bleeding. Material and Methods: This cross-sectional retrospective study was conducted in Bolu İzzet Baysal State Hospital Obstetric and Gynecology outpatient clinic with the complaint of postmenopausal bleeding of 1856 patients' records.within the date of January 2011 - January 2013. Bleeding occurring at least 12 months after amenorhe is defined as postmenaupausal bleeding. A total of 312 patients, who had hystopathologic results, whose endometrial thicknes was measured by TvUSG and who did not use hornonal drug were enrolled in the study. Results: Histological diagnosis of 312 women included in this study; were in atrophy (39.1%) and hyperplasia (simple 18.2% + atypical 6%, respectively) were the most common encountered normal and abnormal endometrial findings. The prevalence of endometrial cancer and atypical hyperplasia was 6.4% (n=20) and 6% (n=19) respectively. Endometrial thickness was significantly higher in the pathologic lesion group than in control (p5 mm is used is a valuable and safe method in evaluation of patients with postmenopausal bleeding. Endometrial curettage is needed in the cases having endometrial thickness above the 5 mm. Copyright © 2013 by Tükiye Klinikleri

postoperative maternal health

To investigate the efficacy of bupivacaine-soaked spongostan in cesarean section wound for postoperative anxiety level, satisfaction and early postpartum depression rate.A total of 121 women, American Society of Anesthesiologists physical status I-II, scheduled to undergo general anesthesia and elective cesarean section were recruited and randomized into a study group (n = 61) or a control group (n = 60). In the spongostan group, bupivacaine-soaked spongostan was placed in the cesarean section wound. The control group did not receive spongostan, but only general postoperative care. Maternal health was assessed using a visual analog scale for satisfaction, a visual analog scale for anxiety and the Edinburgh Postpartum Depression Scale for postpartum depression. Also, first breast-feeding time, first mobilization time and opioid consumption were recorded and compared.The anxiety level of the spongostan group was lower than that of the control group and the difference was statistically significant at all time intervals (1, 6, 12, 18, 24, 30, 36 and 48 h, p < 0.001, respectively). Postpartum depression rate again was significantly lower in the spongostan group both on postoperative day 2 and day 9 (p a parts per thousand currency sign 0.01). All satisfaction scores were significantly higher in the spongostan group than in the control group (p < 0.001). Additionally, first breast-feeding and first mobilization times were significantly shorter and opioid consumption was lower in the spongostan group (p < 0.001).Placement of bupivacaine-soaked spongostan into the cesarean section wound resulted in decreased postoperative anxiety level and postpartum depression rate and increased satisfaction