Immunoreactive ghrelin in human cord blood: relation to anthropometry,leptin, and growth hormone

BACKGROUND: Ghrelin is secreted by the stomach, the hypothalamus, and the placenta in humans and has growth hormone-secreting and orexigenic properties. Leptin is secreted mainly by the adipocyte, plays a major role in energy balance, and reflects fat mass in infants as well as adults. Leptin and ghrelin central effects are mediated, at least partly, through the neuropeptide Y/Y1 receptor pathway in the hypothalamus. METHODS: We determined whether ghrelin is also present in the fetus and investigated its relationship to leptin, growth hormone, birth weight, and calf and abdominal circumferences in 90 full-term neonates. RESULTS: Immunoreactive ghrelin was detected in all cord samples (mean +/- SD, 187 +/- 88 pmol/L; range, 66-594 pmol/L). In contrast to leptin, ghrelin concentrations of boys and girls were not statistically different. In female neonates, ghrelin is inversely correlated with anthropometric measures. In male neonates, ghrelin is positively correlated with leptin and negatively with growth hormone. CONCLUSION: The presence of significant ghrelin concentrations in all neonates before the first feeding is intriguing. Unlike the fairly constant concentrations and effects of leptin over the short term, the wide variability of ghrelin concentrations observed in newborns raises the possibility that ghrelin secretion causes short-term changes in feeding behavior. We suggest that ghrelin may play a physiologic role in the initiation of feeding.     

Effects of dietary PCB exposure on adrenocortical function in captive American kestrels (Falco sparverius)

We experimentally examined the effects of dietary exposure to polychlorinated biphenyls (PCBs) on adrenocortical function in American kestrels (Falco sparverius). Nine captive male American kestrels previously exposed to a PCB mixture (Aroclor1248:1254:1260; 1:1:1) in their diet were subjected to a standardized capture, handling and restraint protocol designed to produce an increase in circulating corticosterone. A similar protocol has been applied to a wide range of avian species and was used here to evaluate the response of PCB-exposed and control kestrels to a defined physical stressor. Both baseline and stress-induced corticosterone levels were significantly lower in PCB-exposed birds when compared with control birds of the same age. PCB-exposed birds exhibited significantly lower corticosterone levels during the corticosterone response when compared with control birds, independent of body condition. Furthermore, baseline corticosterone concentrations exhibited a hormetic response characterized by an inverted U-shaped dose response in relation to total PCB liver burden. These results support several recent studies which report decreased levels of circulating corticosterone in PCB-exposed wild birds. The results presented here provide the first evidence that exposure to an environmentally relevant level of PCBs (approximately 10 mg/kg body weight) can impair the corticosterone stress response in kestrels, potentially increasing the susceptibility of birds to environmental stressors such as severe weather and predatory and human disturbance.     

Jail-based substance user treatment: an analysis of retention

Many jail inmates have a history of substance use and "abuse"; few, however, receive comprehensive treatment for substance use disorders while in jail. The authors offer a longitudinal reanalysis of data from five jail-based substance user treatment programs. Survival analysis was used to identify client characteristics associated with length of time in treatment. Survival curves for the five programs were compared, indicating which ones retained inmates the longest. Results from a model stratified by jail site revealed that inmates over 25 years of age and those already sentenced had significantly longer treatment stays. The Substance Abuse Intervention Division (SAID) program, a modified therapeutic community in a New York jail, and the Deciding, Educating, Understanding, Counseling, and Evaluation (DEUCE) program, a curriculum-based intervention, had the longest survival curves and were, therefore, most effective at retaining inmates in treatment.     

Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents

Numerous small molecule synthetic tyrosine kinase inhibitors are in clinical development for the treatment of human cancers. These fall into three broad categories: inhibitors of the epidermal growth factor receptor tyrosine kinase family (e.g., Iressa trade mark and Tarceva trade mark ), inhibitors of the split kinase domain receptor tyrosine kinase subgroup (e.g., PTK787/ZK 222584 and SU11248) and inhibitors of tyrosine kinases from multiple subgroups (e.g., Gleevec trade mark ). In addition, agents targeting other tyrosine kinases implicated in cancer, such as Met, Tie-2 and Src, are in preclinical development. As experience is gained in the clinic, it has become clear that unleashing the full therapeutic potential of tyrosine kinase inhibitors will require patient preselection, better assays to guide dose selection, knowledge of mechanism-based side effects and ways to predict and overcome drug resistance.     

Tibial and proximal fibular stress fracture in a rower

Proximal fibular stress fractures are rare injuries that usually result from jumping and running activities of military recruits and athletes. This article describes a female university athlete with proximal lateral leg pain diagnosed by means of a triphase bone scan as proximal fibular stress fracture and proximal to middle one-third tibial stress fracture. This case highlights the need to examine not only the sport but also the athlete's training habits to identify possible factors contributing to the injury. Body type, biomechanics, and gender are also possible etiologic factors.     

Responses of rat spinal neurons to distension of inflamed colon: role of tachykinin NK2 receptors

Tachykinin NK2 receptors are implicated in nociception and the control of intestinal motility. Here we examined their involvement in responses of spinal lumbosacral neurons with colon input to distension of normal or inflamed colon in anesthetized rats. The responses of single neurons to colorectal distension (5-80 mmHg), to electrical stimulation of the pelvic nerve (bypassing sensory receptors) and to somatic stimulation were characterized. The effect of cumulative doses of an NK2 receptor antagonist, MEN 11420 (10-1000 microg kg(-1) IV), on responses to these stimuli was tested in control conditions (n=6), or 45 min after intracolonic instillation of acetic acid (n=6). After colonic inflammation, neuronal responses to colorectal distension and pelvic nerve stimulation were significantly greater. MEN 11420 dose-dependently inhibited the enhanced responses to colorectal distension after inflammation (ID50=402+/-14 microg kg(-1)), but had no significant effect on responses to pelvic nerve stimulation or distension of the normal colon, suggesting a peripheral action selective for the inflamed colon. We conclude that MEN 11420 possesses peripheral anti-hyperalgesic effects on neuronal responses to colorectal distension. These results provide a neurophysiological basis for a possible use of tachykinin NK2 receptor antagonists in treating abdominal pain in irritable bowel syndrome patients.     

Do androgens have a direct effect on endometrial function? An in vitro study

OBJECTIVE: To test the hypothesis that androgens have a direct effect on the function of endometrial epithelial cells. DESIGN: In vitro study. SETTING: Academic research center. PATIENT(S): Endometrial epithelial cells were prepared from biopsy samples obtained from normal fertile women. INTERVENTIONS: Cells were incubated with androstenedione, testosterone, dihydrotestosterone, and DHEA. MAIN OUTCOME MEASURE(S): Secretion of glycodelin A into the culture fluid was used to assess secretory activity. Uptake of (3)H-thymidine and immunostaining for Ki67 was used to assess cell growth. The specific action of the androgens was confirmed by incubation with an antiandrogen, cyproterone acetate. RESULT(S): Androstenedione (10(-6) M and 10(-7) M) caused a dose-dependent decrease in glycodelin A secretion, uptake of (3)H-thymidine, and percentage of positive Ki67 cells in cultured human endometrial epithelial cells. Testosterone, dihydrotestosterone, and DHEA had no effect on glycodelin A secretion or (3)H-thymidine uptake. The direct effect of androgens on endometrial function were confirmed by demonstrating the presence of androgen receptors in cultured endometrial epithelial cells and showing that the direct effects of the androgens were not observed when cyproterone acetate was added to the cultures. CONCLUSION(S): The results suggest that androstenedione can inhibit human endometrial cell growth and secretory activity. Infertility and miscarriage associated with high androgen levels (e.g., that caused by the polycystic ovary syndrome) may be due to an adverse effect of high androgen levels on the endometrium.