Interventions to enhance recovery in healthy workers; a scoping review.

BACKGROUND: Faster recovery from work may help to prevent work-related ill health. AIMS: To provide a preliminary assessment of the range and nature of interventions that aim to improve recovery from cognitive and physical work. METHODS: A scoping review to examine the range and nature of the evidence, to identify gaps in the evidence base and to provide input for systematic reviews. We searched for workplace intervention studies that aimed at enhancing recovery. We used an iterative method common in qualitative research to obtain an overview of study elements, including intervention content, design, theory, measurements, effects and cost-effectiveness. RESULTS: We found 28 studies evaluating seven types of interventions mostly using a randomized controlled study design. For person-directed interventions, we found relaxation techniques, training of recovery experiences, promotion of physical activity and stress management. For work-directed interventions, there were participatory changes, work-break schedules and task variation. Most interventions were based on the conservation of resources and affect-regulation theories, none were based on the effort-recovery theory. The need for recovery (NfR) and the recovery experiences questionnaires (REQ) were used most often. Study authors reported a beneficial effect of the intervention in 14 of 26 published studies. None of the studies that used the NfR scale found a beneficial effect, whereas studies that used the REQ showed beneficial effects. Three studies indicated that interventions were not cost-effective. CONCLUSIONS: Feasible and possibly effective interventions are available for improving recovery from cognitive and physical workload. Systematic reviews are needed to determine their effectiveness.

A randomized clinical trial of the effectiveness of a Web-based health behaviour change support system and group lifestyle counselling on body weight loss in overweight and obese subjects: 2-year outcomes.

BACKGROUND: Weight loss can prevent and treat obesity-related diseases. However, lost weight is usually regained, returning to the initial or even higher levels in the long term. New counselling methods for maintaining lifestyle changes are urgently needed. OBJECTIVES: An information and communication technology-based health behaviour change support system (HBCSS) that utilizes persuasive design and methods of cognitive behavioural therapy (CBT) was developed with the aim of helping individuals to maintain body weight. The purpose of this study was to assess whether CBT-based group counselling combined with HBCSS or HBCSS alone helps to maintain improved lifestyle changes needed for weight loss compared to self-help guidance or usual care. METHODS: A randomized lifestyle intervention for overweight or obese persons (BMI 27-35 kg m-2 and age 20-60 years), recruited from the population registry in the city of Oulu, Finland, was conducted. This study comprised six randomly assigned study arms: CBT-based group counselling (eight sessions led by a nutritionist), self-help guidance-based group counselling (SHG; two sessions led by a nurse) and control, each with or without HCBSS, for 52 weeks. Subjects visited the study centre for anthropometric measurements, blood sample collection and to complete questionnaires at baseline, 12 and 24 months. The main outcome was weight change from baseline to 12 months and from baseline to 24 months. RESULTS: Of the 1065 volunteers screened for the study, 532 subjects (51% men) met the inclusion criteria and were enrolled. The retention rate was 80% at 12 months and 70% at 24 months. CBT-based counselling with HBCSS produced the largest weight reduction without any significant weight gain during follow-up. The mean weight change in this arm was 4.1% [95% confidence interval (CI), -5.4 to -2.8, P < 0.001) at 12 months and 3.4% (95% CI, -4.8 to -2.0, P < 0.001) at 24 months. HBCSS even without any group counselling reduced the mean weight by 1.6% (95% CI, -2.9 to -0.3, P = 0.015) at 24 months. CONCLUSION: The combination of CBT-based group counselling and HBCSS-based weight management is feasible for overweight or obese individuals. Moreover, HBCSS alone could be disseminated to the population at large as an effective means of treating obesity.

Associations of meal frequency and breakfast with obesity and metabolic syndrome traits in adolescents of Northern Finland Birth Cohort 1986.

BACKGROUND AND AIMS: Breakfast consumption and meal frequencies have been linked to the risk of obesity in youth but their associations with metabolic syndrome (MetS) in young populations are yet to be studied. We examined associations of three meal patterns on weekdays--five meals including breakfast, ≤four meals including breakfast and ≤four meals without breakfast--with overweight/obesity and MetS components in Finnish adolescents. METHODS AND RESULTS: A population-based sample of 16-year-old boys and girls (n = 6247) from the Northern Finland Birth Cohort 1986 was used. Adolescents were clinically examined and dietary data were collected using self-administered questionnaires. Overweight/obesity and MetS features were defined according to the International Obesity Task Force cut-offs and the International Diabetes Federation MetS paediatric criteria and their associations with meal patterns assessed using logistic regression, adjusted separately for early life factors (birth size, maternal health) and later childhood factors (health behaviours, weight status, parental education). After adjustment for early life factors, the adolescents who ate five meals/day were at lower risk for overweight/obesity (OR [95% CI] for boys: 0.47 [0.34, 0.65]; girls: 0.57 [0.41, 0.79]), abdominal obesity (OR [95% CI] for boys: 0.32 [0.22, 0.48]; girls: 0.54 [0.39, 0.75]) and hypertriglyceridaemia (boys only). Adjusting for later childhood factors, the five-meal-a-day pattern was associated with decreased odds of overweight/obesity (OR [95% CI] for boys: 0.41 [0.29, 0.58]; girls: 0.63 [0.45, 0.89]) and abdominal obesity in boys (OR 0.32, 95% CI 0.16, 0.63). CONCLUSION: Among 16-year-olds, the five-meal-a-day pattern was robustly associated with reduced risks of overweight/obesity in both genders and abdominal obesity in boys.

Maternal weight gain during the first half of pregnancy and offspring obesity at 16 years: a prospective cohort study.

OBJECTIVE: To assess the association between maternal gestational weight gain (GWG) during the first 20 weeks of gestation and overweight/obesity and abdominal obesity of offspring at the age of 16 years. DESIGN: A prospective cohort study. SETTING: The two northernmost provinces of Finland. POPULATION: Mothers and their adolescent offspring born from singleton pregnancies (3265 boys; 3372 girls) in the Northern Finland Birth Cohort 1986. METHODS: Maternal weight at 20 weeks of gestation was measured in municipal maternity clinics. Maternal GWG was based on the difference between the measured weight and self-reported pre-pregnancy weight, and was classified into quartiles. Offspring weight, height and waist circumference were measured by study nurses during a clinical examination. Logistic regression analyses [with and without adjustment for maternal pre-pregnancy body mass index (BMI), glucose metabolism, education level, haemoglobin, smoking status, parity, and gender of offspring] were performed. MAIN OUTCOME MEASURE: Offspring overweight/obesity, based on BMI and abdominal obesity at 16 years. RESULTS: The highest quartile of maternal weight gain (>7.0 kg during the first 20 weeks of gestation) was independently associated with BMI-based overweight/obesity and abdominal obesity in the 16-year-old offspring (OR 1.46, 95% CI 1.16-1.83, and OR 1.37, 95% CI 1.10-1.72, respectively). Among all covariates, maternal pregravid obesity showed the highest odds for both overweight/obesity and abdominal obesity (OR 4.57, 95% CI 3.18-6.57, and OR 4.43, 95% CI 3.10-6.34, respectively). CONCLUSIONS: Maternal overnutrition during the first half of gestation predicts offspring overweight/obesity and abdominal obesity in adolescence, yet a high pregravid BMI appears to be a more important determinant of both outcomes.

Intergenerational transmission of overweight among Finnish adolescents and their parents: a 16-year follow-up study.

OBJECTIVE: Previous studies have shown strong parental influences on adolescent overweight. However, longitudinal data is scarce on gender-specific effects of parental body mass index (BMI) on offspring overweight. The objective of this study was to examine the associations of parental pre-pregnancy BMI, weight change, BMI and BMI class transition 16 years after pregnancy with the BMI of their 16-year-old children. SUBJECTS AND METHODS: The study population was derived from the general population-based Northern Finland Birth Cohort 1986. A total of 4788 child-mother-father trios (2325 boys, 2463 girls) were analysed. Weight and height of the adolescents were measured and overweight and obesity defined according to the International Obesity Task Force. For the parents, self-reported data were obtained and overweight and obesity defined according to the World Health Organization. Associations of parental BMI status and weight change with offspring BMI were assessed using binary logistic regression analyses stratified by gender and adjusted for parental age and education. RESULTS: Children whose both parents were overweight or obese both before pregnancy and after 16-year follow-up had a strikingly high risk of overweight at age 16 years (boys odds ratio (OR) 5.66 95% confidence interval (CI) 3.12, 10.27; girls OR 14.84 95% CI 7.41, 29.73). Parental pre-pregnancy obesity strongly predicted offspring overweight (mother-son OR 4.36 95% CI 2.50, 7.59; mother-daughter OR 3.95 95% CI 2.34, 6.68; father-son OR 3.17 95% CI 1.70, 5.92; father-daughter OR 5.58 95% CI 3.09, 10.07). CONCLUSION: Parental overweight conveys a major risk for overweight in children for which both parents' long-term overweight (BMI ≥25 kg m(-2) before pregnancy and after 16-year follow-up) was the strongest single predictor. Preventing intergenerational transmission of obesity by helping parents to maintain a healthy weight is an essential target for public health.

The association of body mass index, waist and hip circumference, and waist-hip ratio with Chlamydia pneumoniae IgG antibodies and high-sensitive C-reactive protein at 31 years of age in Northern Finland Birth Cohort 1966.

BACKGROUND: Viruses and bacteria like Chlamydia pneumoniae and Helicobacter pylori have been suggested to have a role in pathogenesis of overweight and obesity. OBJECTIVE: We studied whether C. pneumoniae-specific IgG antibodies are associated with elevated body mass index (BMI), waist and hip circumference, and/or waist-hip ratio (WHR), and whether the risk is more pronounced in the simultaneous presence of an ongoing inflammation as measured by elevated high-sensitive C-reactive protein (hsCRP) levels. SUBJECTS AND METHODS: Our study population was derived from the Northern Finland Birth Cohort 1966 (NFBC1966), a general population sample of 12,058 live-born children. This cross-sectional study consisted of 5044 persons at 31 years of age. Serum C. pneumoniae IgG titers were measured by microimmunofluorescence test, and hsCRP levels by immunoenzymometric assay. RESULTS: C. pneumoniae IgG positivity (titer ≥ 32), both alone and jointly with elevated hsCRP (≥ 1.64 mg l(-1), an upper quartile), was found to significantly associate with elevated BMI in the whole study population and with elevated hip and waist circumference in women, yet no association with WHR was seen. The analyses were adjusted for sex (when appropriate), smoking, socioeconomic position, glucose, insulin, high- and low-density lipoprotein cholesterols, triglycerides, leukocytes and pulse pressure. CONCLUSION: These findings suggest that especially in women, persistent C. pneumoniae infection may be associated with overweight/obesity, independently of more traditional risk factors.

Parental predictors of fruit and vegetable consumption in treatment-seeking overweight children.

BACKGROUND: Information on the role of family dietary behaviours is needed to enable the design of effective interventions for treatment of childhood obesity. The present study aimed to analyse differences in consumption and predictors of fruit, berries and vegetables (FBV) between normal-weight and overweight treatment-seeking children and their parents. METHODS: Fifty-four treatment-seeking overweight and 65 normal-weight 8-year-old children and their parents participated in the present study. Children's and parent's consumption of FBV were assessed by a food frequency questionnaire. Availability of vegetables at home meals, child's preference for FBV and parent's control over portion size were determined. Weight and height were measured and the standardised body mass index of each child was calculated. Multiple linear regression analysis was performed to investigate the predictors of children's FBV consumption. RESULTS: Normal-weight children and parents ate FBV more frequently than overweight children. In the multiple linear regression analysis, mother's (ß = 0.476, P ≤ 0.001) and father's consumption of FBV (ß = 0.347, P = 0.001) and child's preference for eating vegetables (ß = 0.259, P = 0.002) were positively associated with the child's consumption of FBV. In overweight children, parent's consumption of FBV was the only predictor of the offspring's consumption of FBV (P = 0.002). CONCLUSIONS: Predictors related to FBV consumption appear to be the similar in normal-weight and treatment-seeking overweight children. The findings obtained in the present study highlight the importance of parental modelling in determining the consumption of FBV in their children.

Common genetic variation near MC4R is associated with eating behaviour patterns in European populations.

Both rs17782313 (near MC4R) and rs1421085 (FTO) polymorphisms have been consistently associated with increased risk of obesity and with body mass index (BMI) variation. An effect of both polymorphisms on satiety has recently been suggested. We genotyped rs17782313 and rs1421085 in 5764 relatives from 1109 French pedigrees with familial obesity, 1274 Swiss class III obese adults as well as in 4877 French adults and 5612 Finnish teenagers from two randomly selected population cohorts. In all subjects, eating behaviour traits were documented through questionnaires. We first assessed the association of both single nucleotide polymorphisms with BMI and then studied eating behaviour. Under an additive model, the rs17782313-C MC4R allele showed a trend towards higher percentages of snacking in both French obese children (P=0.01) and Swiss obese adults (P=0.04) as well as in adolescents from the Finnish general population (P=0.04). In French adults with familial obesity, this allele tended to be also associated with a higher Stunkard hunger score (P=0.02) and in obese children with a higher prevalence of eating large amounts of food (P=0.04). However, no consistent association of the FTO rs1421085-C allele and available eating behaviour trait was found in our studied populations. The rs17782313-C allele nearby MC4R may modulate eating behaviour-related phenotypes in European obese and randomly selected populations, in both children and adults, supporting a regulatory role of this genetic variant on eating behaviour, as previously shown for MC4R non-synonymous loss-of-function mutations. The potential effect of the obesity-associated FTO gene on eating behaviour deserves additional investigation.

c-Ha-rasVal 12 oncogene-transformed NIH-3T3 fibroblasts display more decondensed nucleosomal organization than normal fibroblasts.

We have compared the nucleosomal organization of c-Ha-rasVal 12 oncogene-transformed NIH-3T3 fibroblasts with that of normal fibroblasts by using micrococcal nuclease (MNase) as a probe for the chromatin structure. The bulk chromatin from asynchronously and exponentially growing ras-transformed cells was much more sensitive to MNase digestion than chromatin from the normal cells. Southern hybridization analyses of the MNase digests with probes specific for the ornithine decarboxylase (odc) and c-myc genes showed that the coding and/or 3' end regions of these growth-inducible genes carry a nucleosomal organization both in ras-transformed and normal cells. Studies with cells synchronized by serum starvation showed that in both cell lines the nucleosomal organization of chromatin is relatively condensed at the quiescent state, becomes highly decondensed during the late G1 phase of the cell cycle, and starts again to condense during the S phase. However, in ras-transformed cells the decondensation state stayed much longer than in normal cells. Moreover, irrespective of the phase of the cell cycle the bulk chromatin as well as that of the odc and c-myc genes was more sensitive to MNase digestion in the ras-transformed cell than in the normal fibroblast. Decondensation of the chromatin was also observed in the normal c-Ha-ras protooncogene-transfected cells, but to a lesser extent than in the mutant ras-transformed cells. Whether the increased degree of chromatin decondensation plays a regulatory role in the increased expression of many growth-related genes in the ras-transformed cells remains an interesting object of further study.

PACAP27 regulates ciliary function in primary cultures of rat brain ependymal cells.

Ependymal cells line the brain ventricles and separate the CSF from the underlying neuronal tissue. The function of ependymal cilia is largely unclear however they are reported to be involved in the regulation of CSF homeostasis and host defence against pathogens. Here we present data that implicates a role of pituitary adenylate cyclase-activating polypeptide (PACAP) in the inhibition of ependymal ciliary function, and also that the PACAP effects are not entirely dependent on adenylyl cyclase activation. Primary ependymal cultures were treated with increasing doses of PACAP27 or adenylyl cyclase toxin (ACT), and ciliary beating was recorded using high-speed digital video imaging. Ciliary beat frequency (CBF) and amplitude were determined from the videos. Ependymal CBF and ciliary amplitude were attenuated by PACAP27 in a concentration- and time-dependent manner. The peptide antagonist PACAP6-27 blocked PACAP27-induced decreases in amplitude and CBF. Treatment with ACT caused a decrease in amplitude but had no effect on CBF, this suggests that the inhibition of CBF and amplitude seen with PACAP27 may not be completely explained by G(s)-AC-cAMP pathway. We present here the first observational study to show that activation of PAC1 receptors with PACAP27 has an important role to play in the regulation of ependymal ciliary function.

Insulin resistance and lipid levels in adolescents with familial risk for psychosis.

OBJECTIVE: Type 2 diabetes and dyslipidemias co-occur frequently with schizophrenia. It is not known how common they are in adolescents with a familial risk for psychosis. METHOD: The Northern Finland 1986 Birth Cohort consists of 9432 children born alive in the two Northernmost provinces in Finland. At the age of 15/16 they participated in clinical examination including measurements of glucose, lipids and IR, and a questionnaire including items about their diet and physical activity. The Finnish Hospital Discharge Register was used to find out non-organic psychoses in parents during 1972-2000. This familial risk was found out in 54 boys and 68 girls. Their results were compared with other cohort members. RESULTS: No differences were observed in the cardiometabolic risk factors between the study groups. CONCLUSION: Our results suggest that familial risk for psychosis is not directly associated with disturbances of glucose and lipid metabolism among adolescents.

Body mass index trajectories from 2 to 18 years - exploring differences between European cohorts.

BACKGROUND: In recent decades, there has been an increase in the prevalence of childhood overweight in most high-income countries. Within northern Europe, prevalence tends to be higher in the UK compared with the Scandinavian countries. We aimed to study differences in body mass index (BMI) trajectories between large cohorts of children from UK and Scandinavian populations. METHODS: We compared BMI trajectories in participants from the English Avon Longitudinal Study of Parents and Children born in 1991-1993 (ALSPAC) (N = 6517), the Northern Finland Birth Cohorts born in 1966 (NFBC1966) (N = 3321) and 1986 (NFBC1986) (N = 4764), and the Danish Aarhus Birth Cohort born in 1990-1992 (ABC) (N = 1920). We used multilevel models to estimate BMI trajectories from 2 to 18 years. We explored whether cohort differences were explained by maternal BMI, height, education or smoking during pregnancy and whether differences were attributable to changes in the degree of skew in the BMI distribution. RESULTS: Differences in mean BMI between the cohorts were small but emerged early and persisted in most cases across childhood. Girls in ALSPAC had a higher BMI than all other cohorts throughout childhood, e.g. compared with the NFBC1986 BMI was 2.2-3.5% higher. For boys, the difference emerging over time (comparing the two NFBC's) exceeded the differences across populations (comparing NFBC1986, ABC and ALSPAC). BMI distribution demonstrated increasing right skew with age. CONCLUSION: Population-level differences between cohorts were small, tended to emerge very early, persisted across childhood, and demonstrated an increase in the right-hand tail of the BMI distribution.

Biomonitoring of 2-(2-alkoxyethoxy)ethanols by analysing urinary 2-(2-alkoxyethoxy)acetic acids.

2-Methoxyacetic and 2-ethoxyacetic acids are well known toxic metabolites of 2-alkoxyethanols. The use of 2-alkoxyethanols is now restricted, and the regulations have forced manufacturers to find substitutive solvents, 2-(2-alkoxyethoxy)ethanols. 2-(2-Alkoxyethoxy)ethanols resemble 2-alkoxyethanols, and their most hazardous similarity is their ability to metabolize to the 2-(2-alkoxyethoxy)acetic acids. In the present study, floor lacquerers' (n = 22) inhalation and total exposure to 2-(2-alkoxy)ethoxyethanols was measured. The measurements of inhalation exposure were done with charcoal tubes, and total exposure was biomonitored by urinalysis of 2-(2-alkoxyethoxy)acetic acids. The 8h inhalation exposures of floor lacquerers to 2-(2-methoxyethoxy)ethanol (DEGME), 2-(2-ethoxyethoxy)ethanol (DEGEE) and 2-(2-butoxyethoxy)ethanol (DEGBE) were in average 0.23 +/- 0.07 ppm (average+/-S.D., n = 3), 0.08 +/- 0.07 ppm (n = 16), and 0.05 +/- 0.03 ppm (n = 16), respectively. The excretions of 2-(2-methoxyethoxy)acetic acid (MEAA), 2-(2-ethoxyethoxy)acetic acid (EEAA) and 2-(2-butoxyethoxy)acetic acid (BEAA) were in average 4.9 +/- 4.3 mmol/mol creatinine, 9.3 +/- 8.0 mmol/mol creatinine and 9.2 +/- 7.4 mmol/mol creatinine, respectively. A linear relationship was found between the urinary 2-(2-alkoxyethoxy)acetic acid concentrations and the preceding 8-h occupational exposure to 2-(2-alkoxyethoxy)ethanol.

Physical activity and fibrinogen concentration in newly diagnosed NIDDM.

OBJECTIVE: To evaluate whether plasma fibrinogen concentration is correlated with the level of physical activity and aerobic power in patients with newly diagnosed non-insulin-dependent diabetes mellitus (NIDDM). RESEARCH DESIGN AND METHODS: We studied 78 middle-aged (54 +/- 6 years, mean +/- SD), obese (body mass index [BMI] 32+/- 5 kg/m2) patients (45 men and 33 women) before and after a 12-month treatment period consisting of either conventional treatment given by community health centers or intensified dietary and exercise education given by a university outpatient clinic. Plasma fibrinogen concentration was measured by using a coagulometer. Physical activity was assessed by a questionnaire, and the patients were classified into a sedentary group or moderately or intensively exercising groups. Aerobic power (maximum oxygen uptake [VO2max], anaerobic threshold [VO2at]) was measured by direct breath-by-breath technique. RESULTS: At baseline, the sedentary patients had higher fibrinogen concentration than those with moderate or high physical activities (3.8 +/- 0.8 vs. 3.3 +/- 0.7 g/l, P < 0.01). Both VO2max and VO2at (ml.min-1.kg-1) showed an inverse linear correlation with fibrinogen (r = -0.38, P < or = 0.001, and r = -0.29, P < 0.01, respectively). In the stepwise multiple regression analysis, BMI, VO2 (ml/min), and smoking were the only significant independent factors explaining 23% of the variance in fibrinogen concentration. In sedentary patients, poor glycemic control was related with high fibrinogen concentration. During the follow-up period, patients maintained, on the average, good to moderate glycemic control. The originally sedentary group showed a decrease in fibrinogen concentration (to 3.3 +/- 0.7 g/l, P < or = 0.001) that reached the same level that the physically more active groups had at baseline. This change was associated with improved glycemic control, but not with any of the other assessed factors, including fatty acid composition of serum lipids reflecting dietary intake of fats. CONCLUSIONS: In addition to BMI and smoking, low reported physical activity and low aerobic power are independently associated with high plasma fibrinogen concentration in newly diagnosed NIDDM.

Association between occupational psychosocial factors and waist circumference is modified by diet among men.

BACKGROUND/OBJECTIVES: Occupational psychosocial stress has been identified as a risk factor for obesity, whereas dietary habits have a key role in weight control. We examined whether dietary habits modify the association between occupational psychosocial factors and waist circumference. SUBJECTS/METHODS: Data comprised 31-year-old men (n=2222) and women (n=2053) in the Northern Finland Birth Cohort 1966. Waist circumference was measured and data on occupational psychosocial factors (demands, control and social support) and other characteristics were obtained through questionnaires. Healthy and unhealthy diet indices were constructed according to the current dietary guidelines. Associations were examined using analysis of variance adjusted for body mass index at age 14, basic education level, leisure-time physical activity, alcohol consumption, smoking, stress-related eating behaviour and parity. RESULTS: Among men, high job demands and high job control were associated with greater waist circumferences, and there were interactions between unhealthy diet and job demands (P=0.043) and job control (P=0.036) in relation to waist circumference. The waist of men with high demands or high control and low consumption of unhealthy foods (red/processed meat, hamburgers and pizzas, fried potatoes, sugar-sweetened soft drinks and white bread) was smaller than that of men with high demands or high control and high consumption of such foods. No associations were found among women. CONCLUSIONS: A diet based on the current dietary guidelines seems to cancel out the adverse effects of occupational psychosocial factors on waist circumference among young men. Longitudinal studies are needed to assess the risks for obesity-related diseases arising from psychosocial work environments and dietary habits.

Characterization of melatonin receptors in the rat suprachiasmatic nuclei: modulation of affinity with cations and guanine nucleotides.

We have characterized melatonin (MT) receptors in the rat suprachiasmatic nuclei by using quantitative autoradiography in vitro at equilibrium conditions for a picomolar affinity site. Binding of the MT agonist 2-[125I]iodomelatonin (30 pM to 6 nM) was saturable, of high affinity (Kd, 52.8 pM), of high specificity, and to a single class of sites (binding capacity, 16.5 fmol/mg protein). However, by shortening the washing time for bound and free ligand, we were able to demonstrate an additional low affinity form of this receptor (Kd, 761 pM; binding capacity, 72.2 fmol/mg protein). Micromolar concentrations of guanine nucleotides and millimolar concentrations of monovalent cations (Na+ and Li+) dose-dependently and specifically inhibited agonist binding at 22 C. Saturation studies revealed that this was due to a decrease in receptor affinity in both cases. Ca+2 promoted high affinity agonist binding, as omission of this cation decreased the affinity of the suprachiasmatic MT receptor. These results suggest coupling of the rat suprachiasmatic MT receptors to guanine nucleotide-binding regulatory protein(s). Moreover, our data demonstrate specific modulation of the affinity of these receptors with cations.

Differential regulation of the rat melatonin receptors: selective age-associated decline and lack of melatonin-induced changes.

To gain some understanding of the factors regulating high affinity melatonin (MT) receptors in the rat, we conducted a series of studies using quantitative autoradiography of [2-125I]iodo-MT binding in vitro with validated assay conditions. MT receptor status and the relative protein content of the autoradiographic sections were assessed in the anterior pituitary gland, the area postrema, the caudal (tail) artery (CA), the anterior cerebral artery (ACA), and the suprachiasmatic nuclei (SCN) of 9-, 96-, and 306-day-old Wistar rats. When age-associated changes in protein content were taken into account, MT receptor expression in the area postrema and the SCN remained relatively constant between 9-306 days of age. On the contrary, a dramatic loss of MT receptors was observed in the arteries of 306-day-old rats (98% and 89% loss compared to the 9-day-old rats in the ACA and CA, respectively). In the anterior pituitary gland, MT receptors were expressed only in the 9-day-old rats. The above changes reflected major changes in binding capacity and minor changes in binding affinity. Neither removal of endogenous circulating MT (acute light exposure for 24 h, pinealectomy, or superior cervical ganglionectomy) nor MT injections (1 mg/kg for 10 days 6 h after lights on) affected MT receptor status in the ACA, CA, area postrema, or SCN. Our data suggest that MT receptor expression is differentially regulated during development and that permanent alterations in MT levels do not affect rat MT receptor status.

Diurnal rhythm of melatonin binding in the rat suprachiasmatic nucleus.

We used quantitative in vitro autoradiography to localize and characterize 2-125I-melatonin binding sites in the rat suprachiasmatic nuclei in relation to pineal melatonin production. In a light:dark cycle of 12:12 h, binding density exhibited significant diurnal variation with a peak at the dark-light transition and a trough 12 hours later. Saturation studies suggested that the decreased binding at light-dark transition might be due to a shift of the putative melatonin receptor to a low affinity state.

Binding of laminin to brain gangliosides and inhibition of laminin-neuron interaction by the gangliosides.

Binding of laminin to glycolipids of neuronal membranes was studied with a thin-layer chromatography overlay assay. The major brain ganglioside GD1A was the main binding component, when chromatograms containing the same molar amount of the different brain gangliosides and the brain sulfatide were incubated with laminin at physiological ionic strength. The possible role of laminin binding to brain gangliosides in laminin-neuron interactions was studied with adhesion assays. It was found that binding of rat brain neurons to laminin is blocked by 10-40 microM brain gangliosides but not by sulfatide. The inhibition by the gangliosides is suggested to be due to competition with the cell surface interaction sites of laminin and not to binding of the gangliosides to the cells. Our findings support the idea that the adhesive and neurite-promoting effect of laminin is dependent on its interaction with gangliosides at the neuronal cell surfaces.