Disease relevance of Nipples

• His major anomalies were microcephaly, synbrachydactyly, diastisis recti, hypospadias, short neck, and widely spaced nipples [1].
• We diagnosed the carbohydrate-deficient glycoprotein syndrome in five children who were seen during their first year of life with failure to thrive, feeding difficulties, psychomotor retardation, hypotonia, esotropia, inverted nipples, lipodystrophy, pericardial effusion, and hepatic dysfunction [2].
• We report on 3 Brazilian brothers born to normal consanguineous parents (F = 1/16) and presenting ectodermal dysplasia, cleft lip/palate, mental retardation, syndactyly of fingers 2-3, accessory nipples, and ear anomalies [3].
• The patient presented mild dysmorphic facial features, inverted nipples, progressive generalized edema, hypertrophic cardiomyopathy, hepatosplenomegaly, muscular hypotonia and had severe hypoalbuminemia [4].
• Prominent manifestations included microcephaly, apparent hypertelorism, epicanthic folds, a broad nasal bridge with anteverted nostrils, posteriorly angulated ears, micrognathia, widely spaced nipples, arachnodactyly with proximal thumbs, and a coxa vara deformity [5].

High impact information on Nipples

• Whereas relaxin is required for development of the mammary nipples in rats and mice, it is essential for prepartum development of glandular parenchyma in pregnant pigs [6].
• Reinstatement was not achieved by coating the washed nipples with the saliva of virgin females eating the same diet, the parturient mother's urine, isotonic saline, amyl acetate, or vanilla extract [7].
• Each agent was dissolved in DMSO, and one-sixth of the total dose was injected under each of six nipples on the right side [8].
• Fluoxetine-induced anaesthesia of vagina and nipples [9].
• N-Nitrosodibenzylamine (NDBzA) is a contaminant found frequently in rubber baby bottle nipples and pacifiers [10].

Chemical compound and disease context of Nipples

• Perinatal administration of 100 or 200 mg vinclozolin (V) kg-1 day-1 during sexual differentiation in rats induces female-like anogenital distance (AGD), retained nipples, cleft phallus with hypospadias, suprainguinal ectopic scrota/testes, a vaginal pouch, epididymal granulomas, and small to absent sex accessory glands in male offspring [11].
• A case of hyperkeratosis of the nipples in a patient with adenocarcinoma of the prostate treated with diethylstilbestrol is described herein [12].

Biological context of Nipples

• The nipples of rlx-/- animals do not enlarge significantly during pregnancy, and their histology retains the appearance of the virgin state [13].
• We recently demonstrated that relaxin-dependent development of the mammary nipples during the second half of pregnancy is required for pup survival during lactation in the rat [14].
• An almost fully feminized phenotype of 10-12 nipples was observed in animals that had malformations in T-dependent tissues, whereas 6 or more nipples were observed in animals with malformation in DHT-dependent tissues [15].
• These findings indicate that the burst amplitude mainly depends on the amount of afferent suckling signals arising from the nipples on the side opposite to the recording side, and that there may exist bilateral summation centres coordinating with the synchronization mechanism of milk-ejection bursts of oxytocin neurones [16].
• Hypertrophic nipples were seen in 42% of surviving female fetuses prenatally exposed to 2.0 mg/kg of ethinyl estradiol singly on day 11 of gestation [17].

Anatomical context of Nipples

• First, the presence of specific relaxin binding in the epithelial cells of the lactiferous duct, smooth muscle cells, and skin of the nipples in nonpregnant rats was identical to the sites of specific relaxin binding in the nipples of pregnant rats [18].
• The objective of the present study was to identify the cells containing specific relaxin-binding sites in the uterine cervix, vagina, uterus, mammary glands, mammary nipples, and term placenta in the human [19].
• We conclude that the specific relaxin-binding cells in the cervix, mammary glands, nipples, small intestine, and skin of the pregnant pig probably contain relaxin receptors and, therefore, mediate relaxin's effects in these tissues [20].

Associations of Nipples with chemical compounds

• We conclude that relaxin stimulates the growth of rat mammary nipples at least in part through direct actions in the nipples, and that estrogen is not required for these actions [18].
• Tissue cross-sections (6 microns) obtained from the midpoint of mammary nipples were stained with either Gomori's trichrome stain (to visualize collagen) or orcein (to visualize elastin) [14].
• As adults, flutamide-exposed males had nipples [21].
• These data also suggest that although linuron-mediated retention of areolae on PND 13 and nipples at necropsy may be suggestive of altered testosterone-mediated reproductive development seen in adult rats, these endpoints are not predictive [22].
• Only DDE-treated animals retained nipples on PND 13 [23].

Gene context of Nipples

• Mutant females deficient for the Lgr7 receptor have grossly undeveloped nipples and are unable to feed their progeny [24].
• We also demonstrate that CK7, but not CK20, highlights intraepidermal clear cells with bland nuclear features (Toker cells) that have been reported in 11% of normal nipples [25].
• The total amount of immunoreactive CGRP was significantly higher in the nipples from the pregnant and the lactating rats when compared to SP [26].
• Plasma PRL levels were low in rats separated from their litters, but they increased when pups were returned to the cage, attached to the nipples of the mother, and suckled [27].
• Mothers which had previously suckled 12 pups (Group 1) showed a graded increase in the amount of oxytocin released during a 3 h suckling test when the number of pups applied to the nipples was increased from six to eight or ten [28].

Analytical, diagnostic and therapeutic context of Nipples

• To examine relaxin-induced growth of the mammary nipples, 5 days after ovariectomy, 48 nonpregnant rats were assigned (12 rats/group) to 1 of the following 4 treatment groups: ovariectomized controls, estrogen treated, relaxin treated, and estrogen plus relaxin treated [18].
• Radioimmunoassay and immunohistochemistry of nipples from lactating rats treated with capsaicin as neonates revealed a marked depletion of SP-I [29].
• So-called 'sugar nipples' delivering small amounts of sucrose orally at the time of a painful procedure in an infant has been not been shown to decrease vaccination pain and studies on refrigerant topical anesthetics are mixed [30].
• Prospectively, 93 nipples were reconstructed by a single surgeon using a modified star dermal fat flap technique in 44 implant and 49 TRAM flap breast reconstructions [31].
• After treatment with 0.150 mg ethinylestradiol per day for 9 months, moderate breast enlargement occurred and the nipples became the size of normal female nipples [32].

References