Adaptive variability in the duration of critical windows of plasticity: Implications for the programming of obesity

Developmental plasticity underlies widespread associations between early-life exposures and many components of adult phenotype, including the risk of chronic diseases. Humans take almost two decades to reach reproductive maturity, and yet the ‘critical windows’ of physiological sensitivity that confer developmental plasticity tend to close during fetal life or infancy. While several explanations for lengthy human maturation have been offered, the brevity of physiological plasticity has received less attention. I argue that offspring plasticity is only viable within the niche of maternal care, and that as this protection is withdrawn, the offspring is obliged to canalize many developmental traits in order to minimize environmental disruptions. The schedule of maternal care may therefore shape the duration of critical windows, and since the duration of this care is subject to parent–offspring conflict, the resolution of this conflict may shape the duration of critical windows. This perspective may help understand (i) why windows close at different times for different traits, and (ii) why the duration of critical windows may vary across human populations. The issue is explored in relation to population differences in the association between infant weight gain and later body composition. The occupation of more stable environments by western populations may have favoured earlier closure of the critical window during which growth in lean mass is sensitive to nutritional intake. This may paradoxically have elevated the risk of obesity following rapid infant weight gain in such populations.     

Maternal iron deficiency identifies critical windows for growth and cardiovascular development in the rat postimplantation embryo

Imbalances in nutrition during pregnancy can lead to long-, as well as short-term consequences, a phenomenon known as fetal programming. However, there is little information about when the fetus is most sensitive to its environment during gestation. We hypothesize that different fetal systems are most vulnerable to nutritional stress during periods of maximal growth and differentiation. We used iron (Fe) deficiency, which causes hypertension in the offspring, to test this hypothesis. We examined development between embryonic day (E) 10.5 and 12.5, when cardiovascular development is maximal, using whole embryo culture. Female rats were fed Fe-deficient or control diet for 4 wk before mating and up to E10.5. The embryos were cultured for 48 h in 95% rat serum collected from males fed either a control or Fe-deficient diet. Growth was impaired and heart size increased in embryos taken from Fe-deficient mothers and cultured in deficient serum compared with control embryos cultured in control serum. To test whether restoring normal Fe levels could reverse these effects, we cultured embryos from control and deficient dams in either control or deficient medium. The yolk sac circulation of embryos from dams fed either diet cultured in deficient medium was less developed, with a thinner and less branched network than that in all embryos cultured in control serum. The heart was enlarged in embryos of deficient dams cultured in deficient serum compared with the heart size of those cultured in control serum. Culturing embryos in control serum reversed these changes. We conclude, therefore, that this period of cardiovascular organogenesis is one of the sensitive windows during which optimal Fe status is critical for normal development.     

Long-term effects of whole-body vibration: a critical survey of the literature

Summary The relevant literature on the long-term effects of whole-body vibration (wbv) was analyzed in order to obtain condensed information concerning a possibly higher health risk due to long-term exposure, the relationships between the quality of exposure (intensity, duration, frequency) and pathological effects, the significance of individual factors, conclusions for standard setting, and medical health care of workers exposed to wbv. Vibration exposure was characterized by measured values in one third of papers, whereas more than 30% of the publications selected did not contain any exposure data. Health data of about 43 000 workers exposed to wbv and 24 000 persons in control groups were reported.The results indicate an increased health risk of the spine and of the peripheral nervous system after intense long-term wbv. With a lower probability, the digestive system, the peripheral veins, the female reproductive organs, and the vestibular system were also affected. Long-term effects on other organs cannot be precluded. Wbv can worsen certain endogenous conditions. Specific diagnostic features of pathological changes induced by wbv with frequencies below 20 Hz do not exist. On average, the health risk increases with higher intensity or duration of exposure, however, quantitative exposure-effect relationships cannot be derived at present. Since wbv near the Exposure Limit of the International Standard IS 2631 is not completely safe, this survey provides arguments in favour of a lower limit. Contra-indications for professional exposure to wbv and further research needs are discussed.The authors gratefully acknowledge the help and assistance of Mrs. R. Vizcaino     

Long-term effects on adiposity after preweaning nutritional manipulations in the gastrostomy-reared rat

Male Long-Evans rat pups were either fed by continuous intragastric infusion of a milk formula to match the growth rate of their normally reared siblings, or overfed by continuous infusion of a fat-supplemented formula from d 4 through d 18 postpartum. The early overfeeding accelerated growth and the overfed rats remained significantly heavier than normally reared siblings as adults. Early overfeeding with this procedure led to an adult obesity at 14 mo characterized by significantly larger epididymal and retroperitoneal fat depots resulting from an increase of both fat cell size and number, and by an increase in adipose tissue lipoprotein lipase activity. Gastrostomy rearing per se, without overfeeding, resulted in adult rats that weighed the same as normally reared siblings but had significantly larger retroperitoneal fat depots because of more adipocytes. These findings suggest that the quantity of food consumed during early growth and development, and the quality of early nutrition and/or the early rearing environment affect adipose tissue development and have long-term consequences that persist in the rat.     

Long-term effects of nutritional group education for persons at high cardiovascular risk

BACKGROUND: Treatment of persons at high risk for coronary heart disease (CHD) should include nutritional counselling, but little is known about the effects of different types of education. METHODS: In a quasi-experimental study design the effects of a nutritional education programme (1st year: three group sessions by a dietitian; 2nd year: one group session; 3rd year: additional focus on saturated fat; reinforcement by written nutritional messages annually) (intervention group; n=103) are compared with the effects of a posted leaflet containing standard dietary guidelines (control group; n=163). Participants had hypercholesterolemia (6-8 mmol/l) and at least two other CHD risk factors. RESULTS: After 3 years, no significant differences existed in established CHD risk factors between intervention and control groups (adjusted mean net differences: total cholesterol (0 mmol/l), diastolic blood pressure (-1.1 mm Hg; NS), and body weight (+0.3 kg, NS)). Regarding dietary intake, the intervention group had a lower intake of total (net difference -2.0% of energy, SEM 0.9) and saturated fat (-1.2% of energy, SEM 0.4) and a higher fish (+11 g/day, SEM 4) and vegetables consumption (+21 g/day, SEM 10) during the study period (p<0.05 for all). CONCLUSION: A nutritional education programme with group sessions changed dietary intake more effectively than a posted leaflet, but no additional positive effects were observed on established CHD risk factors after three years of follow-up.     

Identifying critical windows of exposure for children's health

Several authors have considered the importance of exposure timing and how this affects the outcomes observed, but no one has systematically compiled preconceptional, prenatal, and postnatal developmental exposures and subsequent outcomes. Efforts were undertaken to examine the information available and to evaluate implications for risk assessment for several areas: a) respiratory and immune systems, b) reproductive system, c) nervous system, d) cardiovascular system, endocrine system, and general growth, and e) cancer. Major conclusions from a workshop on "Critical Windows of Exposure for Children's Health" included a) broad windows of sensitivity can be identified for many systems but detailed information is limited; b) cross-species comparisons of dose to target tissue and better data on the exposure-dose-outcome continuum are needed; c) increased interaction among scientific disciplines can further understanding by using laboratory animal results in designing epidemiological studies and human data to suggest specific laboratory studies on mechanisms and agent-target interactions; and d) thus far, only limited attention has been given to peripubertal/adolescent exposures, adult consequences of developmental exposures, and genome-environment interactions. More specific information on developmental windows will improve risk assessment by identifying the most sensitive window(s) for evaluation of dose-response relationships and exposure, evaluation of biological plausibility of research findings in humans, and comparison of data across species. In public health and risk management, information on critical windows may help identify especially susceptible subgroups for specific interventions.     

Myopathies in critical illness: characterization and nutritional aspects

Myopathies related to critical illness have received increasing recognition over the past decade and are common in patients even after a brief period in the intensive care unit. Recent studies have revealed that myopathies in the critically ill may in fact be more prevalent than neuropathies and that morbidity and mortality may be greater. Protein catabolism, an increase in urinary nitrogen loss, and muscle wasting are observed in critical illness myopathy. Muscle biopsies in critically ill patients demonstrate low glutamine levels, low protein/DNA levels, and high concentrations of extracellular water. The increased flux of glutamine in muscle in these patients is thought to be insufficient to meet the body's requirement for glutamine, and thus in critical illness this amino acid may be classified as "conditionally essential." Three subtypes of critical illness myopathy have been described that are often grouped together as acute quadriplegic myopathy: thick-filament myopathy, critical illness myopathy, and necrotizing myopathy. These can be differentiated based on clinical features and muscle biopsy. Treatments for critical illness myopathies range from primary prevention, i.e., avoiding myopathy-inducing drugs, to novel nutritional therapies, such as glutamine and glutathione supplementation. One should be particularly vigilant for the development of myopathies in critically ill alcoholic patients, who may have a chronic alcoholic myopathy at baseline. In the past decade, advances have been made in characterizing and identifying patients with myopathies due to critical illness. However, additional studies must be performed in order to develop appropriate therapies for this potentially devastating disorder.     

Mathematical models of the embryo and fetus for use in radiological protection

This development of new mathematical models arose from our current work in external neutron dosimetry for the embryo and fetus when pregnant women travel at commercial aircraft altitudes. A problem of concern in radiation protection is exposure of pregnant women to ionizing radiation because of the high radiosensitivity of the embryo and fetus. Special regulations and dosimetric considerations are necessary for pregnant women at the work place and in the public. To perform dosimetry, mathematical models for the embryo and the fetus, together with the modified adult female model for pregnant woman, are required. There are no models available for embryo. Models developed for the fetus need to be updated with the new reference values such as those in ICRP Publication 89. This article presents mathematical models for the embryo and fetus at different stages: the embryo at 8 wk and the fetus at the end of each trimester. In addition to fetal skeleton, the fetal brain is explicitly modeled because of its high radiosensitivity. All model parameters are determined from the most recent reference values available. The models are designed so that an interpolation can be easily performed to generate a model of embryo/fetus at any given stage of development. This feature also allows convenient adaptation of the models to different reference values representing various ethnic populations. The new mathematical models presented here were developed for external dosimetry. They can also be used for internal dosimetry purposes, if other organs inside the female phantom are adjusted accordingly.     

血清前白蛋白评价胎儿营养状况的研究

目的 探讨血清前白蛋白对胎儿营养状况的评价.方法 分别检测足月与早产新生儿脐血血清前白蛋白及母亲血清前白蛋白水平,正常体重与低出生体重新生儿脐血血清前白蛋白与母亲血清前白蛋白水平,并对有关数据进行比较分析.结果 足月儿与早产儿母亲血清前白蛋白比较无显著性差异(t=0.75,P>0.05),足月儿与早产儿脐血血清前白蛋白比较有显著性差异,(t=4.55,P<0.01);正常体重儿与低出生体重儿母亲和新生儿脐血血清前白蛋白水平的比较均有显著性差异(t值分别为4.33、5.73,均P<0.05).结论 血清前白蛋白对孕妇及胎儿营养状况有评价作用.血清前白蛋白水平可成为反映围产因素造成胎儿宫内营养不良的敏感指标.     

Long-term nutritional and digestive consequences of pelvic radiation

OBJECTIVE: To study long-term changes in nutritional status and gastrointestinal (GI) functions of 15 women previously treated with radiotherapy for gynecological cancer. Two years prior to this research, these patients had been assessed twice: before external radiotherapy and 5 weeks later, at the completion of the external dose (45-50 Gy). METHODS: Each patient was given complete clinical evaluation, consisting of dietary, physical activity and digestive symptoms questionnaires. Blood was drawn for routine clinical laboratory tests (hemoglobin, white blood cell count, creatinine, lipoproteins, glucose, total proteins, albumin, and C reactive protein). Body composition was assessed by classical anthropometric indicators and double beam X-ray absorptiometry (DEXA), while muscle strength was measured through a hand dynamometer. Resting energy expenditure (REE), obtained by indirect calorimetry, was subtracted from energy ingestion, derived from dietary records, to calculate energy balance. RESULTS: This third evaluation included fifteen patients. A significant increase in body mass index (BMI), % body fat and waist circumference were observed in comparison to earlier evaluations. The lean compartment decreased significantly, and REE descended in parallel. Meanwhile, total energy, fat and protein intake increased, compared to previous measurements. The changes in bowel habits observed during radiotherapy persisted at this third evaluation, with the exception of diarrhea, which was less reported. Abdominal bloating and rectal symptoms were the most prevalent complaints. CONCLUSIONS: After radiation treatment for gynecological cancer, patients gained more body fat than expected in Chilean women around menopause. In spite of high protein ingestion, the loss of fat-free mass observed during radiation treatment was not recovered along with weight increase. This is probably associated with infrequent physical activity, both during and after treatment, and hyperphagia.     

On the mechanisms relevant to nutritional carcinogenesis

Prevention of the nutritionally linked cancers will be on a sounder footing eventually if the measures recommended not only are consonant with international epidemiological data and the results of laboratory experimentation, but also rest on an understanding of the mechanisms of action of the various nutritional factors. The process of cancer causation involves a series of steps that can be classified broadly into (a) the definition of DNA-reactive carcinogens and (b) the assessment of enhancing or inhibiting epigenetic agents. For cancers highly prevalent in the Western world, especially of the breast, colon, and pancreas, and perhaps also of the prostate, evidence has begun to accrue that a new type of heterocyclic amine formed during cooking of meat or fish constitutes the DNA-reactive carcinogen. The type and amount of fat play a role in enhancing the effect of epigenetic mechanisms that characteristically are highly sensitive to dosage and duration. These epigenetic phenomena are also reversible. Cereal fiber, by increasing stool bulk, dilutes epigenetic promoters in the intestinal tract. Therefore, based on mechanistic understanding, reduction in risk is feasible by lowering fat, increasing fiber, and perhaps by altering cooking modes.     

Estimates of absorption of radiofrequency radiation by the embryo and fetus during pregnancy.

This paper reports that the specific absorption rate induced in the embryo or fetus can exceed that recommended for the general public when the mother is exposed to radiofrequency radiation at the occupational limits. This result applies to two-tiered radiofrequency radiation standards where a factor of 5 differentiates occupational and nonoccupational exposure limits. Using simple axisymmetric geometries for the pregnant worker, and assuming plane wave exposures, a finite element method provides estimates of prenatal exposure. Various layered shapes are used to model skin, fat, uterus, blood, embryonic, and fetal tissues. Applying current exposure limits given by IRPA, ANSI, and SAA, the results indicate that overexposures to the embryo or fetus can occur from early pregnancy at 80-100 MHz, and in late pregnancy across the range 300-1500 MHz.     

危重病人营养与代谢支持策略的演变

已认识到全肠外营养在危重病人营养支持中的不足,主要是感染和肝功能的并发症较难克服。与全肠外营养相比,肠内营养具有并发症少,费用低等优点。但由于外科病人通过肠道进行营养支持有一定限制。为避免能量与蛋白质供给不足,可采用肠内 肠外的营养支持模式。过多供给能量与蛋白质,不仅不能改善病人的营养状态,反而对机体有害,危重病人的合理营养支持最好是按实际测量的能量消耗供给营养底物,要想进一步改善重危病人营养支持的效果。必须注重辅助疗法的应用。如谷氨酰胺、精氨酸、亚油酸、短链脂肪酸以及微生态营养。     

Determination of nutritional status in critical care

The application of the standard battery of nutritional assessment tests, measurements, and calculations is of limited value in the immediate nutritional diagnosis of the critically ill patient. Many of these tests are affected by stress, making it impossible to distinguish the etiology of abnormalities during the early postinjury period. Altered test results because of stress or injury include: increased excretion of creatinine; increased white blood cell (WBC) counts; increased anergy to skin tests; and decreased serum albumin, transferrin, thyroxin-binding prealbumin, and retinol-binding protein concentrations. Therefore, in assessing the nutritional status of the critically ill patient, it is important to focus on indexes that are realistic relative to the patient's metabolic status. Timing of data collection is of keen importance; data collected after fluid resuscitation and the peak metabolic response to injury on postinjury days 5 through 10 are usually more meaningful than those collected immediately after hospital admission. Admission assessment is necessary only to identify the high-risk patient in need of immediate nutrition intervention, to estimate energy/nutrition and fluid requirements, and to provide guidelines for planning nutrition care. This article presents recommendations for initial assessment, postcatabolism assessment, and serial assessment of the critically ill patient. Guidelines for estimating energy/nutrient requirements and timing data collection are also presented.     

The mammalian respiratory system and critical windows of exposure for children's health

The respiratory system is a complex organ system composed of multiple cell types involved in a variety of functions. The development of the respiratory system occurs from embryogenesis to adult life, passing through several distinct stages of maturation and growth. We review embryonic, fetal, and postnatal phases of lung development. We also discuss branching morphogenesis and cellular differentiation of the respiratory system, as well as the postnatal development of xenobiotic metabolizing systems within the lungs. Exposure of the respiratory system to a wide range of chemicals and environmental toxicants during perinatal life has the potential to significantly affect the maturation, growth, and function of this organ system. Although the potential targets for exposure to toxic factors are currently not known, they are likely to affect critical molecular signals expressed during distinct stages of lung development. The effects of exposure to environmental tobacco smoke during critical windows of perinatal growth are provided as an example leading to altered cellular and physiological function of the lungs. An understanding of critical windows of exposure of the respiratory system on children's health requires consideration that lung development is a multistep process and cannot be based on studies in adults.