Enhancing diurnal cortisol regulation among young children adopted internationally: A randomized controlled trial of a parenting-based intervention.

Children who have been adopted internationally commonly experience institutional care and other forms of adversity prior to adoption that can alter the functioning of the hypothalamic-pituitary-adrenal (HPA) axis. In particular, internationally adopted children tend to have blunted diurnal declines compared to children raised in their birth families. The Attachment and Biobehavioral Catch-Up (ABC) intervention was developed to enhance young children's biological and behavioral regulation by promoting sensitive parenting. The current study used a randomized controlled trial to assess whether ABC improved the diurnal functioning of the HPA axis among 85 children who had been adopted internationally when they were between the ages of 4 and 33 months (M = 16.12). Prior to the intervention, there were no significant differences in diurnal cortisol production between children whose parents were randomly assigned to receive ABC and children whose parents were randomly assigned to receive a control intervention. After the intervention, children whose parents had received the ABC intervention exhibited steeper declines in cortisol levels throughout the day than children whose parents had received the control intervention. These results indicate that the ABC intervention is effective in enhancing a healthy pattern of diurnal HPA axis regulation for young children who have been adopted internationally.

Intervening to enhance cortisol regulation among children at risk for neglect: Results of a randomized clinical trial.

The hypothalamus-pituitary-adrenal axis is particularly sensitive to conditions of maltreatment. In particular, neglected children have shown a flatter slope with lower wake-up values relative to nonneglected children. An intervention, the Attachment and Biobehavioral Catch-Up (ABC), was developed to enhance biological and behavioral regulation in young children at risk for neglect. The effectiveness of the intervention was assessed in a randomized clinical trial for children with involvement with Child Protective Services. Following the intervention, children receiving the ABC intervention (n = 49) showed more typical cortisol production, with higher wake-up cortisol values and a steeper diurnal slope, than children receiving the control intervention (n = 51). These results suggest that the ABC intervention is effective in enhancing biological regulation.

Persistence of hormonal and metabolic rhythms during fasting in 7- to 9-day-old rabbits entrained by nursing during the night.

Rabbit does nurse their litter once every 24h during the night. We hypothesized that corticosterone, ghrelin, leptin, and metabolites such as glucose, liver glycogen, and free fatty acids could be affected in the pups by the time at which does nurse them. Therefore, we measured these parameters in pups nursed at 02:00 h (nighttime for the doe) to compare them with results from a previous study where does nursed at 10:00 h, during daytime. From postnatal day 7, pups were sacrificed either just before their scheduled time of nursing or at 4, 8, 12, 16, or 20 h after nursing (n=6 at each time point); additional pups were sacrificed at 4h intervals between 48 and 72 h after nursing to study the persistence of oscillations during fasting. All pups developed locomotor anticipatory activity to nursing. Corticosterone, ghrelin, and free fatty acids exhibited a rhythm that persisted in fasted pups. Glucose concentrations were lower in fasted than in nursed pups, and glycogen was only detected in nursed subjects. Leptin values were stable and low in nursed subjects but increased significantly in fasted subjects up to 72 h after the expected nursing time. The rhythm of ghrelin persisted during fasting, contrary to our previous findings in pups nursed during daytime (i.e., outside the natural time of nursing for this species). Therefore, in 7-day-old rabbit pups, night nursing is a strong zeitgeber for corticosterone, ghrelin, free fatty acids, and energy metabolites but not for leptin.

Measurement of the lowest dosage of phenobarbital that can produce drug discrimination in rats.

RATIONALE: Accurate measurement of the threshold dosage of phenobarbital that can produce drug discrimination (DD) may improve our understanding of the mechanisms and properties of such discrimination. OBJECTIVES: This study aimed to compare three methods for determining the threshold dosage for phenobarbital (D) versus no-drug (N) DD. MATERIALS AND METHODS: Rats learned a D versus N DD in two-lever operant training chambers. A titration scheme was employed to increase or decrease dosage at the end of each 18-day block of sessions depending on whether the rat had achieved criterion accuracy during the sessions just completed. Three criterion rules were employed, all based on average percent drug lever responses during initial links of the last six D and six N sessions of a block. The criteria were: D% > 66 and N% < 33; D% > 50, and N% < 50; (D% - N%) > 33. Two squads of rats were trained, one immediately after the other. RESULTS: All rats discriminated drug versus no drug. In most rats, dosage decreased to low levels and then oscillated near the minimum level required to maintain criterion performance. The lowest discriminated dosage significantly differed under the three criterion rules. The squad that was trained second may have benefited by partially duplicating the lever choices of the previous squad. CONCLUSIONS: The lowest discriminated dosage is influenced by the criterion of discriminative control that is employed and is higher than the absolute threshold at which discrimination entirely disappears. Threshold estimations closer to absolute threshold can be obtained when criteria are employed that are more permissive of errors and that allow rats to maintain lever preferences.

Hormonal and metabolic rhythms associated with the daily scheduled nursing in rabbit pups.

Young rabbits are nursed every 24 h for a period of 3-5 min. As a consequence, pups are synchronized to this nursing event; this synchronization is characterized by increased locomotor activity and a peaking of core temperature and plasma corticosterone in anticipation of the daily meal. Ghrelin is a hormone suggested to play a role in meal initiation and to promote food intake. The present study explored the role of ghrelin in food-entrained conditions. Newborn rabbits were maintained in constant darkness and nursed once daily at 1000 by the lactating dam. On postnatal day 7, rabbits were killed at six different time points to complete a 24-h cycle. All pups developed locomotor rhythms entrained by mealtime and exhibited anticipatory activity. Food-entrained rhythms in plasma corticosterone and free fatty acids were observed even if two meals were omitted. In contrast, daily food-driven rhythms in stomach weight, plasma glucose, liver glycogen, and ghrelin did not persist when two meals were omitted. Peak ghrelin levels were observed at the moment in the cycle when the stomach weight was lowest, i.e., before initiation of anticipation. The present data are in agreement with previous data from rabbit pups maintained in light-dark conditions and provide evidence that 7- to 9-day-old rabbits in constant darkness can exhibit metabolic and hormonal rhythms mainly driven by the restricted daily nursing.

Foster children's diurnal production of cortisol: an exploratory study.

Young children in foster care have often experienced inadequate early care and separations from caregivers. Preclinical studies suggest that early inadequate care and separations are associated with long-term changes in regulation of the hypothalamic-pituitary-adrenal (HPA) axis. In this study, the daytime pattern of cortisol production was examined among 55 young children who had been placed into foster care and 104 children who had not. Saliva samples were taken at wake-up, in the afternoon, and bedtime for 2 days. Average salivary cortisol values for each time of day were computed. A group (foster vs. comparison) time (morning, afternoon, night) interaction emerged, reflecting less decline in levels across the day for foster than comparison children. Daytime patterns were categorized as typical, low, or high. Children who had been in foster care had higher incidences of atypical patterns of cortisol production than children who had not. These differences suggest that conditions associated with foster care interfere with children's ability to regulate neuroendocrine functioning.

Effect of flavored beverage crystals on salivary cortisol enzyme-immunoreactive assay measurements.

We examined the effects of using flavored drink crystals as a salivary stimulant on salivary cortisol values. The effects of both amount and method of flavored crystal administration on cortisol values were evaluated using a high sensitivity enzyme immunoassay (EIA) kit to measure cortisol. Repeated saliva sampling, one sample without the drink crystal stimulant, followed immediately by a second sample using the drink crystal stimulant, allowed direct analysis of the effect of the stimulant on cortisol values. Repeated sampling, with the stimulant used when obtaining both the first and second samples, allowed analysis of the repeatability of cortisol measurements using the drink crystals. The results suggest that the use of drink mix crystals as an oral stimulant causes a small increase in measured cortisol values, as well as an increase in the variability of these values. The results also suggest that the effect of drink crystals is sufficiently regular so that it will not distort either within or between subject comparisons as long as there is consistency in use or non-use of the stimulant.

Circadian rhythm of corticosterone secretion in the neonatal rabbit.

Maternal care in the rabbit is restricted to a single 3- to 5-min period of nursing each day. One to three hours prior to the arrival of the mother, pups exhibit anticipatory behavioral arousal and elevation of core body temperature. In rodents, the hypothalamic-pituitary-adrenal axis is quiescent and levels of the adrenal hormone, corticosterone (CORT), are stable and extremely low during the first days of life, which are known collectively as the stress-hyporesponsive period (SHRP). It has been proposed that the rabbit also has an SHRP. However, we decided to examine CORT changes associated with the daily nursing bout, since behavioral arousal, core body temperature, and CORT are elevated prior to the onset of feeding in many other species. We scheduled the nursing bout at 1000 h and analyzed CORT concentration using RIA in pups sampled at various intervals after suckling. CORT levels showed a circadian variation that peaked at the time of the daily nursing bout. After nursing, values steadily decreased to a nadir at 2200 h and then rose again in advance of the next scheduled nursing. The three-fold difference between the highest (1000 h) and the lowest (2200 h) CORT values suggests that either the SHRP does not exist in rabbit pups or else it has properties that differ from those described for rodents. Unlike rodents, rabbit pups show a circadian secretion of CORT synchronized to the scheduled nursing bout.

Prevalence of cusp fractures in teeth restored with amalgam and with resin-based composite.

BACKGROUND: Complete cusp fracture in restored teeth is a common problem observed in general dental practice. Many dentists believe that teeth restored with amalgam are more likely to be associated with cusp fractures than are those restored with resin-based composite. METHODS. The authors noted the condition of 10,869 posterior teeth with amalgam or resin-based composite restorations with at least one cusp present, unrestored or missing in 1,902 consecutively seen adult patients in a private general dental practice. For each patient, the authors recorded age, type of restorations, number of surfaces of each restoration, and presence or absence of a complete cusp fracture and of caries. RESULTS: There was a lower percentage of cusp fractures in younger subjects than in older subjects and in teeth with a single restored surface than in those with more than one restored surface. There was no significant difference in the prevalence of cusp fracture rates in amalgam-restored teeth versus composite-restored teeth in subjects aged 18 through 54 years. In subjects aged 55 through 96 years, there was a marginally significantly greater cusp fracture rate in composite-restored teeth than in those restored with amalgam. Overall, there was no significant difference in the prevalence of cusp fracture in teeth restored with amalgam (1.88 percent) versus composite-restored teeth (2.29 percent). CONCLUSIONS: The prevalence of cusp fractures in amalgam-restored teeth and resin-based composite-restored teeth is not significantly different. Teeth with more than one surface restored with either resin-based composite or amalgam and teeth in older subjects were more likely to suffer a cusp fracture. CLINICAL IMPLICATIONS: Teeth restored with amalgam and with resin-based composite exhibited equally low cusp fracture prevalence. When choosing between amalgam and resin-based composite in consideration of the likelihood of a future cusp fracture, either restorative material is acceptable.

Differential expression of c-fos and tyrosine hydroxylase mRNA in the adrenal gland of the infant rat: evidence for an adrenal hyporesponsive period.

Rats exhibit a stress hyporesponsive period from postnatal day (PND) 4-14 in which the neonate displays a minimal corticosterone response to stress. We used the maternal deprivation model to test whether this adrenocortical hyporesponsiveness to stress results from a decrease in adrenal sensitivity to ACTH. Neonates (PND 6, 9, and 12) were injected ip with dexamethasone to block endogenous ACTH release, and 4 h later injected with graded doses of ACTH and killed. In another experiment, neonates were injected with isotonic saline and adrenal glands were collected at 30, 60, and 120 min post injection to examine c-fos and tyrosine hydroxylase mRNA levels using in situ hybridization. Maternally deprived pups demonstrated elevated corticosterone levels at the two highest ACTH doses and showed a greater magnitude in glucocorticoid secretion compared with the nondeprived pups. Maternally deprived pups given a saline injection exhibited elevated basal and stress-induced levels of corticosterone, in contrast to the nondeprived pups that showed a minimal response. Strikingly, maternally deprived pups exhibited elevated levels of adrenocortical c-fos mRNA, whereas the nondeprived pups did not. In contrast, the pattern of c-fos gene expression in the adrenal medulla in both groups did not display any correlation with glucocorticoid secretion. Tyrosine hydroxylase gene expression in the adrenal medulla was observed in both nondeprived and maternally deprived pups, with the latter exhibiting an earlier response of greater magnitude. These results demonstrate that the suppression of steroidogenesis occurs directly in the adrenal cortex and provide further evidence for an adrenal hyporesponsive period in the rat.

Injection pain of bupivacaine with epinephrine vs. prilocaine plain.

BACKGROUND: Prilocaine plain has been described in the literature as causing less pain on injection than bupivacaine with epinephrine, possibly because of the higher pH of the prilocaine anesthetic solution. METHODS: In a double-blind study design, 681 consecutive patients in a general dental practice received maxillary buccal infiltration, posterior palatal infiltration or inferior alveolar block injections, administered under clinical conditions by one of two dentists. Immediately after injection, patients rated the pain from each injection on a six-point scale. The pain response was analyzed according to treating dentist, location of injection, patient's sex and anesthetic administered. RESULTS: The reported pain on injection of bupivacaine with epinephrine was significantly greater than that of prilocaine plain. Patients reported no significant difference in pain at different injection locations, except that palatal injections caused significantly more reported pain than did anterior maxillary infiltration, posterior maxillary infiltration or inferior alveolar block injections. CONCLUSIONS: Under clinical conditions, the injection of bupivacaine with epinephrine causes significantly more perceived pain than does the injection of prilocaine plain. Clinical Implications. Bupivacaine with epinephrine and prilocaine plain have certain advantages and disadvantages that should be considered before choosing an anesthetic for a dental procedure. A disadvantage of bupivacaine with epinephrine is that it produces more perceived pain than does prilocaine plain.