Flow cytometric measurement of HLA-DR expression on circulating monocytes in healthy and sick neonates using monocyte negative selection

The aim of this study was to investigate the effect of prematurity, neonatal sepsis, respiratory distress syndrome (RDS) and perinatal asphyxia on monocyte HLA-DR expression of neonates using a flow cytometric method based on monocyte negative selection. The subjects were one hundred and thirty-one neonates (59 healthy, 44 septicaemic, 20 with RDS and eight with perinatal asphyxia) and 20 healthy adults. Monocyte HLA-DR expression was measured using one-colour HLA-DR labelling in a gate for monocytes obtained using the combination of CD3-CD19--PE/CD15--FITC MoAbs. In addition, the common dual staining method using MoAbs against two CD14 epitopes (TUK4, MO2) was evaluated. With the one-colour HLA-DR labelling higher purity and recovery values of monocytes were achieved than with the dual labelling METHOD: Healthy neonates had significantly lower percentages of HLA-DR(+) monocytes than adults (69 +/- 13% versus 91.5 +/- 2.5%) and comparable mean fluorescence intensity (MFI) (119 +/- 25 versus 131 +/- 26). Values did not differ significantly between healthy term and preterm neonates. Preterm neonates with RDS had a significantly lower percentage of HLA-DR(+) monocytes than the healthy preterm neonates. In neonates with asphyxia both parameters were comparable to those of the healthy ones. Septicaemic neonates presented significantly lower values of both parameters than the healthy, RDS and asphyxiated neonates. Monocyte negative selection provides a reliable estimation of HLA-DR expression on monocytes. Expression of monocyte HLA-DR is lower in healthy neonates in comparison with adults and is further decreased in neonates with sepsis and RDS, but it is not influenced by prematurity and perinatal asphyxia.     

Neutrophil adhesion molecule expression in the developing neonatal rat exposed to hyperoxia

Neonatal rats have an increased tolerance to hyperoxia, which is associated with a diminished pulmonary inflammatory response compared with adults. To investigate this differing response, expression of the neutrophil adhesion molecules, L-selectin and CD18, and levels of soluble L-selectin, were examined using flow cytometry and sandwich enzyme-linked immunosorbent assay on air-exposed neonatal rat neutrophils at 0-24 and 72 h and 7, 10, 14, and 21 d of age compared with the adult and after exposure to hyperoxia (>/= 98% O2) for 56 h in adults and for 72 h and 7 d in neonates. Expression of L-selectin in 0-24-h neonates was similar to adults, but was significantly lower than adults at 72 h and 7 d (P = 0.011). Soluble L-selectin levels were significantly higher than those in adults in the 0-24- and 72-h neonates (P < 0.001). CD18 expression in unstimulated and activated neutrophils of neonatal rats was higher at 0-24 h than in the adult (P < 0.001), but thereafter did not differ from adults. After hyperoxic exposure, L-selectin did not differ between the exposure groups but soluble L-selectin tended to increase in neonates after 7 d of O2 exposure Finally, CD18 was significantly higher after hyperoxic exposure of the adult (P = 0.008), but did not change with oxygen exposure in the neonate. Based on these findings, we speculate that differences between neonatal and adult rats in expression of L-selectin may contribute to delayed oxygen toxicity in neonatal rats.     

Effects of neonatal oxytocin treatment on aggression and neural activities in mandarin voles

Neonatal manipulation of oxytocin (OT) has long-term effects on behavior and physiology. Here we test the hypothesis that neonatal OT treatment can affect the subsequent expression of intrasexual aggression partly by reprogramming the neural activities of relevant brain regions. To test this hypothesis, mandarin voles (Lasiopodomys mandarinus) received OT or isotonic saline treatment within 24 h of birth. At about 75 days of age, aggressive behaviors and Fos expression in different brain regions were tested. The results indicate that the (1) level of intrasexual aggression was higher and other social contact was lower in SAL-treated sexually na?ve males than in females and; (2) OT-treated females showed a greater increase in aggressive behaviors and Fos expression only after exposure to a male than SAL-treated females, but there were no significant changes in aggressive behaviors in males. These results demonstrate a sexual difference in aggression, and that neonatal exposure to OT may increase aggression in female mandarin voles. These effects may be based on changes in neural activities of relevant brain regions including the bed nucleus of the stria terminalis (BNST), lateral septal nucleus (LS), medial preoptic area (MPOA), the paraventricular nucleus of the hypothalamus (PVN), supraoptic nucleus (SON), mediodorsal thalamic nucleus (MD), ventromedial nucleus of hypothalamic (VMH), the medial amygdala (MeA) and central amygdala (CeA).     

Assessment of brain oxygenation in term and preterm neonates using near infrared spectroscopy

PurposeThe aim of this study was to determine brain oxygenation in full-term and preterm neonates using near infrared spectroscopy.Material and methodsA total of 88 full-term and preterm newborn infants without hypoxic-ischaemic disorders admitted to the NICU were examined using NIRS on the first day of life and on day 28 of life. Additional measurements were taken at the end of the first week of life in the premature neonates group. Measurements of oxyhaemoglobin (HbO2), deoxyhaemoglobin (Hb), total haemoglobin (HbT) concentration and tissue oxygen saturation (Ox) were performed in 5 brain regions. Right and left frontal areas, the occipital area and right and left temporal areas were measured.ResultsIn full-term healthy neonates a marked decrease in HbO, Hb and HbT values was observed on day 28 of life in all brain regions except the occipital area. In the neonatal period the greatest changes in brain oxygenation occurred in the right and left frontal regions of the brain. In preterm neonates constant values of HbO2 and Ox were observed in the first 28 days of life. In preterm newborn infants, as well as in full term newborn infants, similar Ox and HbO2 values were obtained on day 28 of life.ConclusionsNIRS is a safe method and can be used to evaluate brain oxygenation in newborn infants. The results of these measurements are in accordance with changes in brain oxygenation in the first month of life, which are predicated on the basis of the neonate's physiology.     

Association between Daily Sunlight Exposure and Fractures in Older Korean Adults with Osteoporosis: A Nationwide Population-Based Cross-Sectional Study

PurposeWe aimed to investigate the association between daily sunlight exposure duration and fractures in older Korean adults with osteoporosis.Materials and MethodsWe utilized data from the 2008–2011 Korea National Health and Nutrition Examination Survey. Osteoporosis was diagnosed based on a T-score of ≤−2.5 using dual energy X-ray absorptiometry. The duration of daily sunlight exposure and fracture were assessed via intensive health interviews by trained staff using standardized health questionnaires. Fracture was defined as one or more fractures of the femur, wrist, and spine.ResultsA total of 638 patients with osteoporosis aged ≥65 years were included. The odds ratio (OR) of total fractures was 0.55 times lower in the group with ≥5 h of daily sunlight exposure than in the group with <5 h of exposure after adjusting for age, sex, family history of osteoporosis or fracture, body mass index, bone mineral density of the femoral neck, serum 25-hydroxyvitamin D, current smoking, alcohol intake, daily calcium intake, and physical activity [95% confidence interval (CI) 0.31–0.97, p=0.040]. In patients with vitamin D insufficiency, the OR of total fracture was 0.52 times lower in the group with ≥5 h of daily sunlight exposure than in the group with less exposure after adjusting the above variables (95% CI 0.28–0.97, p=0.041).ConclusionSunlight exposure for ≥5 h a day was significantly associated with a decreased OR of fracture in older Korean adults with osteoporosis. This association was also significant in patients with vitamin D insufficiency.     

Validity of microsphere model in cerebral blood flow measurement using N-isopropyl-p-(I-123) iodoamphetamine

A microsphere model is sometimes used when calculating cerebral blood flow (CBF) using N-isopropyl-p-[I-123]iodoamphetamine (IMP), and is based on the assumption that there is essentially no washout of IMP. The validity of a microsphere model was investigated by comparison with the values of CBF obtained by means of a model which takes into consideration the diffusion of IMP from brain tissue to blood (nonmicrosphere model). When calculating CBF by the latter model, the look-up table method was used with expression of the double integral in the model equation by the recursion relations, a method which is useful for obtaining pixel-by-pixel values. The average rate constants for diffusion from brain to blood of gray and white matter were 0.021 and 0.0016 min-1, respectively. The values of CBF obtained by applying a microsphere model to the data acquired from 0 to 3.2 min after IMP injection were overestimated by approximately 23% compared with those values obtained using a nonmicrosphere model. This is considered to be due to the effect of the IMP activity in the vascular space. Values obtained using the data acquired from 3.2 to 6.4 min were underestimated by approximately 15%. When the values of CBF obtained by a microsphere model were interpolated, they became nearly equal to those obtained using a nonmicrosphere model at about 4 to 5 min after injection. This is suggested to be the reason why the underestimation due to diffusion from brain to blood is cancelled out by the overestimation due to the IMP in the vascular space. Our preliminary results suggest that it is necessary to take the diffusion of IMP from brain tissue to blood into account for the quantification of CBF using IMP.     

A thermoregulation model for hypothermic treatment of neonates

This paper presents a thermoregulation finite element model (FEM) to simulate hypothermia procedures for the treatment of encephalopathy hypoxic-ischemia (EHI) in neonates, a dangerous ischemic condition that can cause neurological damages and even death. Therapeutic hypothermia is the only recommended technique to reduce sequels caused by EHI in neonates; intervention with moderate cooling for neural rescue in newborns with hypoxic-ischemic brain injury is the culmination of a series of clinical research studies spanning decades. However, the direct monitoring of brain cooling is difficult and can lead to additional tissue damage. Therefore, the measurement of efficiency during clinical trials of hypothermia treatment is still challenging. The use of computational methods can aid clinicians to observe the continuous temperature of tissues and organs during cooling procedures without the need for invasive techniques, and can thus be a valuable tool to assist clinical trials simulating different cooling options that can be used for treatment. The use of low cost methods such as cooling blankets can open the possibility of using brain cooling techniques in hospitals and clinics that cannot currently afford the available expensive equipment and techniques. In this work, we developed a FEM package using isoparametric linear three-dimensional elements which is applied to the solution of the continuum bioheat Pennes equation. Blood temperature changes were considered using a blood pool approach. The results of the FEM model were compared to those obtained through the implementation of a user-defined function (UDF) in the commercial finite volume software FLUENT and validated with experimental tests. Numerical analyses were performed using a three-dimensional mesh based on a complex geometry obtained from MRI scan medical images.     

Immunophenotyping of blood lymphocytes at birth, during childhood, and during adulthood in HIV-1-uninfected Ethiopians

To obtain more insight into blood lymphocyte subpopulations of Ethiopians, we studied the immunologic profile of children and neonates and compared these data with those obtained from adults. Peripheral blood mononuclear cells (PBMCs) and cord blood mononuclear cells (CBMCs) were collected from 137 HIV-1-uninfected subjects aged 0 (cord blood) up to 40 years. Lymphocyte subsets (T, B, and NK cells, CD4+ and CD8+ T cells) were determined and T cell activation (CD38 and HLA-DR) and differentiation (CD45RO and CD27) markers were measured on CD4+ and CD8+ T cells. The absolute number and percentage values of most lymphocyte subpopulations differed substantially with age. Neonates and children were found to have significantly higher CD4+ T cell counts compared to adults. The median absolute CD4 count at birth was comparable to those reported for Caucasians. At birth 97% of the CD4+ T cells were na?ve and this proportion significantly declined to 14.2% during adulthood. In addition, activation of both CD4+ and CD8+ T cells, as determined by the double expression of HLA-DR and CD38, was observed in children under the age of 16 and adults, but not in neonates. A more differentiated phenotype (CD27-) was observed in adults compared to children for both CD4+ and CD8+ T cells. The immune alterations including the remarkably low CD4 count with highly depleted na?ve phenotype and a persistently activated immune system seen in adult Ethiopians are not apparent at birth, but rather develop over time.     

Hematological abnormalities during the first week of life among neonates with trisomy 18 and trisomy 13: data from a multi-hospital healthcare system

Limited information is available on the expected hematological values of newborn infants with trisomy 18 or trisomy 13 syndromes. About 50% of patients with these conditions survive beyond the first week of life, and some have complete blood counts (CBCs) obtained to assist in medical management. We tabulated all CBC data that had been obtained on patients with either trisomy, during their first week of life, using data from an 18 hospital healthcare system. We posited that describing the CBC findings would assist clinicians in providing care for these patients who survive beyond the first days. During the period of January 1, 2001 through December 31, 2006, 174,480 live births were recorded at the 18 hospitals. Trisomy 18 was recognized in 28 (prevalence estimate, 1 in 6,231) and trisomy 13 in 22 (prevalence estimate, 1 in 7,931). Twenty-four of these had one or more CBCs obtained before the seventh day. Thrombocytopenia was the most common hematological abnormality detected, occurring in 83% of those with trisomy 18 and 75% of those with trisomy 13. Three patients with trisomy 18, and 1 with trisomy 13, received platelet transfusions. The second most commonly detected abnormality was neutrophilia. Eighty-three percent of neonates with trisomy 13, and 42% with trisomy 18, had neutrophil concentrations above the upper limit of normal for age. Abnormal erythrocyte values were the third most common hematological abnormalities detected. These were much more common among neonates with trisomy 18. Only 43% of patients with trisomy 18 had normal erythrocyte values; anemia was detected in 40% and polycythemia in 17%. Only one neonate with trisomy 13 had abnormal erythrocyte findings (polycythemia). These data should assist clinicians caring for neonates with trisomy 18 or 13, demonstrating how common hematological abnormalities exist among these patients.     

Pharmacokinetics of fluconazole in pediatric patients

The pharmacokinetic properties of fluconazole were studied in more than 100 pediatric patients, including 12 premature neonates. The volume of distribution and the rate of elimination differed significantly from the values reported for adults. The volume of distribution varied with age, being greatest during the neonatal period (1.18 to 2.25 l/kg) and decreasing by young adulthood to a value similar to that reported for adults (0.7 l/kg). With the exception of neonates, fluconazole clearance was generally more rapid in children than in adults, with a mean plasma elimination half-life of just over 20 h for all pediatric age groups. In neonates, fluconazole was eliminated slowly, with a mean elimination half-life of 88.6 h at birth, 67.5 h approximately one week later and 55.2 approximately two weeks after birth. Fluconazole appeared to be well absorbed from the gastrointestinal tract. These pharmacokinetic results, taken in conjunction with the corresponding data for adults, provide a sound basis for establishing appropriate fluconazole dosage recommendations for pediatric patients.     

The accuracy of artificial and natural light measurements by actigraphs

Actigraphs are the reference standard for measuring light exposure in human non‐laboratory experiments due to their portability and long battery lives. However, actigraphs typically have a limited illuminance operating range not representative of real‐world conditions, and for many actigraphs, the accuracy of their light measurement has not been verified independently. We assessed the illuminances recorded by Activinsights GENEActiv Original and Philips Actiwatch 2 actigraphs in comparison to a calibrated, laboratory‐standard photometer, under both artificial light‐emitting diode (LED) and natural sunlight illuminations that might be encountered by a person under real‐world conditions. We show that in response to ~20,000 lux white LED light, the GENEActiv and Actiwatch 2 underestimate illuminance by recording 50% and 25% of the true value, respectively. Under ~30,000 lux sunlight, the GENEActiv readily saturates whereas the Actiwatch 2 reports ~46% of the true illuminance. These underestimations are highly linear and we provide correction factors to estimate the illuminance levels of the ambient environment measured by the actigraphs. We also evaluate the application of neutral density filters for extending the operating range of both devices in natural sunlight illuminations (as high as 30,000 lux during our measurements) and demonstrate that this may be a viable approach for increasing the operating range of the Actiwatch 2 but not the GENEActiv. We conclude that both actigraphs provide good performance in monitoring the temporal patterning of light, whereas the absolute illuminance values require correction to accurately evaluate the effects of light intensity on human health and behaviours.     

Effect of hyperthermia and anoxia on glucocorticoid and mineralocorticoid receptor expression in neonatal rat hippocampus

Brief periods of neonatal asphyxia are frequently observed. Within the CNS, the hippocampus is known to be particularly vulnerable to the damaging effects of hypoxia/ischaemia. The hippocampus contains the highest concentration of both mineralocorticoid (MR) and glucocorticoid (GR) receptors and the balance between MR/GR activation influences cell birth and death. MR occupation appears to promote prosurvival actions, while GR overactivation favours neurodegeneration. It has been widely recognized that core body temperature is a critical determinant of the severity of hypoxic–ischemic brain injury; indeed, hyperthermia exacerbates the degree of damage. Therefore, the aim of the present investigation was to study the effect of elevated body temperature in newborn rats under control conditions or during neonatal exposure to a critical anoxia, on changes of MR and GR mRNA expression in the rat hippocampus. 2-day-old rats were exposed to anoxia in 100% nitrogen atmosphere. Rectal temperature was kept at 33 °C (typical for the rat neonates), or elevated to a level typical for febrile (39 °C) adults. Control rats were exposed to atmospheric air under the respective thermal conditions. The changes in MR and GR mRNA expression in hippocampus were examined 24 h after exposure. Our data show that hyperthermia with or without added anoxia, causes induction of MR mRNA expression in neonatal rat hippocampus without any effect on GR mRNA expression. We suggest this elevation of MR plays an important role in modulating the survival of neurons in the injured hippocampus.     

Oxytocin modulates the racial bias in neural responses to others’ suffering

The intergroup relationship between a perceiver and a target person influences empathic neural responses to others’ suffering, which are increased for racial in-group members compared to out-group members. The current study investigated whether oxytocin (OT), a neuropeptide that has been linked to empathic concern and in-group favoritism, contributes to the racial bias in empathic neural responses. Event-related brain potentials were recorded in Chinese male adults during race judgments on Asian and Caucasian faces expressing pain or showing a neutral expression after intranasal self-administration of OT or placebo. A fronto-central positive activity at 128–188 ms (P2) was of larger amplitude in response to the pain expressions compared with the neutral expressions of racial in-group members but not of racial out-group members. OT treatment increased this racial in-group bias in neural responses and resulted in its correlation with a positive implicit attitude toward racial in-group members. Our findings suggest that OT interacts with the intergroup relationship to modulate empathic neural responses to others’ suffering.     

Magnetic resonance imaging of ischemic injury produced by varying severities of photothrombosis differs in neonatal and adult brain

Stroke is a major cause of disability in adults and children. Recently, we have developed an adult rat model of minor stroke containing a peri‐infarct region with a modest T₂ increase and mild ischemic damage. We hypothesized that a neonatal minor stroke with mild peri‐ischemic changes could also be produced, but with potential ontogenic differences. Using our minor photothrombosis method, we produced a range of severities of ischemic lesions (mini, minor, moderate and severe) within magnetic resonance imaging (MRI) slices of adult and neonatal rats. In both age groups, the lesion region showed a marked increase in T₂ and diffusion‐weighted intensity and decrease in apparent diffusion coefficient (ADC), corresponding to a cortical infarct detected using fluorojade and hematoxylin and eosin staining. Perilesional regions showed modest increases in T₂ and ADC in adults, but not neonates, and this corresponded to scattered cell death, but not necessarily extravasation of plasma protein, i.e. blood–brain barrier disruption. Mini and minor insults in neonates generally showed homogeneous and rather modest changes in T₂ and ADC. MR perfusion maps demonstrated a penumbral area of greater hypoperfusion in adults compared with neonates. Together, the results indicate that, in neonatal cortex, a similar severity of photothrombosis occurs throughout the area of photoactivation, whereas, in adult brain, spontaneous clot lysis and/or partial thrombosis occurs adjacent to permanently occluded vessels. Thus, by comparing differing severities of photothrombotic ischemia in neonates and adults, ontogenic differences were detectable using MRI, with mature brain having a greater penumbral region. Mild ischemic injury and scattered cell death in both neonates and adults could be identified by a modest increase in T₂ and decrease in ADC. A better understanding of the effects of development on ischemic responses and associated MRI changes will provide a basis for the improved diagnosis of mild or minor ischemic insults relevant to pediatric and adult stroke.     

Chronic morphine treatment inhibits oxytocin release from the supraoptic nucleus slices of rats

Effect of chronic morphine treatment on oxytocin (OT) release from the long term-cultured organotypic slice of the supraoptic nucleus (SON) was investigated using radioimmunoassay. The co-localization of oxytocin and mu-opioid receptor in neurons within the SON was observed with the double-labeled methods of in situ hybridization combined with immunohistochemistry. After exposure to morphine for 6days, the OT levels in culture media were significantly decreased. Naloxone caused much greater release of OT in chronic morphine treatment group than in controls. Naloxone has no effect after acute morphine treatment. 90% of OT-ir (immunoreactive) neurons expressed mu-opioid receptor mRNA in the SON and 45% of the neurons that expressed mu-opioid receptor mRNAs were OT-ir neurons. These results indicated that the neurons within SON could develop dependence on morphine in vitro, and these effects might be exerted via mu-opioid receptor in oxytocin neurons of the SON.     

Effects of monocytes from human neonates on lymphocyte transformation

Adherent cells (approximately 75% monocytes, 25% lymphocytes) obtained from neonates and from adults were studied to compare their effects on mitogen-induced lymphocyte transformation. The response of autologous lymphocytes to concanavalin A (Con A) was enhanced significantly by adherent cells from neonates and from adults. Whereas the addition of 2-mercaptoethanol (2-ME) did not enhance the response of unseparated peripheral blood mononuclear cells or fully restore the response of adherent cell-depleted lymphocytes from neonates, both of these effects were observed when 2-ME was added to cell preparations from adults. In fact, the response to Con A of lymphocytes from adults was significantly greater in the presence of 2-ME than in the presence of autologous adherent cells. Equivalent enhancement of the response to Con A was observed when adherent cells from neonates were added to lymphocytes from adults or when adherent cells from adults were added to lymphocytes from neonates.

Adherent cells from neonates consistently inhibited the autologous lymphocyte response to the specific B-cell mitogen, NWSM, a water-soluble extract of Nocardia opaca. Lymphocytes from five out of nine neonates failed to respond to NWSM unless adherent cells were depleted. The presence of adherent cells did not prevent the response of lymphocytes from any of the eight adults tested. This difference in response to NWSM between lymphocytes from neonates and adults was significant. Inhibition of the response of autologous lymphocytes to NWSM by adherent cells from adults was of lesser magnitude and could be demonstrated consistently only when 2-ME was added to adherent cell-depleted lymphocyte preparations. We conclude that the effects of adherent cells which were observed were due to monocytes. The enhancing effect of monocytes from adults on lymphocyte response to Con A could be replaced by 2-ME, whereas this was not true for neonates. In contrast to their effects on response to Con A, monocytes from neonates inhibited the response to NWSM more consistently and to a greater degree than did monocytes from adults.

     

Natural summer and winter sunlight exposure patterns in seasonal affective disorder

Twelve subjects with winter depression who lived in the Chicago area recorded their times of going outside during daylight hours for one week during the winter and one week during the summer. These records produced estimates of the duration of daily sunlight exposure and of perceived dawn, dusk and skeleton photoperiod. There was more than twice as much sunlight exposure in summer compared to winter (3.0 vs. 1.2 h/day). The perceived skeleton photoperiod was 4-5 h longer in summer than winter, with a later perceived dusk contributing more to the lengthening than an earlier perceived dawn. The duration of sunlight exposure and perceived skeleton photoperiod in both seasons was much less than what was possible given the available daylight. These results are discussed with reference to the modern urban life style, bright light treatment of winter seasonal affective disorder, and factors which affect the perceived intensity of sunlight.     

Detection of Cancerous Masses in Mammograms by Template Matching: Optimization of Template Brightness Distribution by Means of Evolutionary Algorithm

Optimization of brightness distribution in the template used for detection of cancerous masses in mammograms by means of correlation coefficient is presented. This optimization is performed by the evolutionary algorithm using an auxiliary mass classifier. Brightness along the radius of the circularly symmetric template is coded indirectly by its second derivative. The fitness function is defined as the area under curve (AUC) of the receiver operating characteristic (ROC) for the mass classifier. The ROC and AUC are obtained for a teaching set of regions of interest (ROIs), for which it is known whether a ROI is true-positive (TP) or false-positive (F). The teaching set is obtained by running the mass detector using a template with a predetermined brightness. Subsequently, the evolutionary algorithm optimizes the template by classifying masses in the teaching set. The optimal template (OT) can be used for detection of masses in mammograms with unknown ROIs. The approach was tested on the training and testing sets of the Digital Database for Screening Mammography (DDSM). The free-response receiver operating characteristic (FROC) obtained with the new mass detector seems superior to the FROC for the hemispherical template (HT). Exemplary results are the following: in the case of the training set in the DDSM, the true-positive fraction (TPF) = 0.82 for the OT and 0.79 for the HT; in the case of the testing set, TPF = 0.79 for the OT and 0.72 for the HT. These values were obtained for disease cases, and the false-positive per image (FPI) = 2.     

Neonatal oxytocin manipulations have long-lasting, sexually dimorphic effects on vasopressin receptors

Developmental exposure to oxytocin (OT) or oxytocin antagonists (OTAs) has been shown to cause long-lasting and often sexually dimorphic effects on social behaviors in prairie voles (Microtus ochrogaster). Because regulation of social behavior in monogamous mammals involves central receptors for OT, arginine vasopressin (AVP), and dopamine, we examined the hypothesis that the long-lasting, developmental effects of exposure to neonatal OT or OTA might reflect changes in the expression of receptors for these peptides. On postnatal day 1, prairie voles were injected intraperitoneally with either OT (1 mg/kg), an OTA (0.1 mg/kg), saline vehicle, or were handled only. At approximately 60 days of age, vasopressin V1a receptors, OT receptors (OTR) and dopamine D2 receptor binding were quantified using receptor autoradiography in brain tissue taken from males and females. Significant treatment effects on V1a binding were found in the bed nucleus of the stria terminalis (BNST), cingulate cortex (CgCtx), mediodorsal thalamus (MdThal), medial preoptic area of the hypothalamus (MPOA), and lateral septum (LS). The CgCtx, MPOA, ventral pallidum, and LS also showed significant sex by treatment interactions on V1a binding. No significant treatment or sex differences were observed for D2 receptor binding. No significant treatment difference was observed for OTR receptor binding, and only a marginal sex difference. Changes in the neuropeptide receptor expression, especially the V1a receptor, may help to explain sexually dimorphic changes in behavior that follow comparable neonatal manipulations.     

Theoretical limits on brain cooling by external head cooling devices

Numerous experimental studies have demonstrated that mild hypothermia is a rather promising therapy for acute brain injury in neonates. Because measurement of the resultant cooling of human brain in vivo is beyond current technology, an understanding of physical factors limiting the possible brain cooling would be a substantial achievement. Herein brain cooling by external head cooling devices is studied within the framework of an analytical model of temperature distribution in the brain. Theoretical limits on brain hypothermia induced by such devices are established. Analytical expressions are obtained that allow evaluation of changes in brain temperature under the influence of measurable input parameters. We show that a mild hypothermia can be successfully induced in neonates only if two necessary conditions are fulfilled: sufficiently low cerebral blood flow and sufficiently high value of the heat transfer coefficient describing the heat exchange between the head surface and a cooling device.