The reduction of astrocytes and brain volume loss in anorexia nervosa-the impact of starvation and refeeding in a rodent model.

Anorexia nervosa (AN) is an often chronic, difficult to treat illness that leads to brain volume reductions in gray and white matter. The underlying pathophysiology is poorly understood, despite its potential importance in explaining the neuropsychological deficits and clinical symptoms associated with the illness. We used the activity-based anorexia model (ABA), which includes food reduction and running wheel access in female rats to study brain changes after starvation and refeeding. Longitudinal animal MRI and post-mortem brain sections confirmed a reduction in the mean brain volumes of ABA animals compared to controls. In addition, the mean number of astrocytes was reduced by over 50% in the cerebral cortex and corpus callosum, while the mean number of neurons was unchanged. Furthermore, mean astrocytic GFAP mRNA expression was similarly reduced in the ABA animals, as was the mean cell proliferation rate, whereas the mean apoptosis rate did not increase. After refeeding, the starvation-induced effects were almost completely reversed. The observation of the astrocyte reduction in our AN animal model is an important new finding that could help explain starvation-induced neuropsychological changes in patients with AN. Astrocyte-targeted research and interventions could become a new focus for both AN research and therapy.

Exposure to Famine in Early Life and Nonalcoholic Fatty Liver Disease in Adulthood.

CONTEXT: Epidemiologic studies have indicated that early life nutrition influences later risk of obesity, type 2 diabetes, and metabolic syndrome. Nonalcoholic fatty liver disease (NAFLD) is also considered a metabolic disease. OBJECTIVE: The aim was to explore the association between adult NAFLD and fetal or childhood exposure to Great Chinese Famine between 1959 and 1962 during fetal and childhood period. DESIGN AND SETTING: In total, 5306 subjects from the Survey on Prevalence in East China for Metabolic Diseases and Risk Factors study were divided into a fetal-exposed (1959-1962), childhood-exposed (1949-1958), adolescence/young adult-exposed (1921-1948), and nonexposed (1963-1974, reference) group. MAIN OUTCOME MEASURE: The degrees of steatosis of NAFLD were determined by ultrasonography. RESULTS: The prevalences of NAFLD in the nonexposed (1963-1974), fetal-exposed, and childhood-exposed participants were 55.9%, 55.8%, and 55.4% in men and 33.0%, 46.3%, and 51.7% in women, respectively. Compared with those nonexposed, fetal- and childhood-exposed women but not men had a significantly higher prevalence of moderate-severe steatosis (P < .05). A significant association existed in women between increased alanine aminotransferase and both fetal and childhood exposure to famine, after adjusting for age, rural/urban residence, economic status, body mass index, diabetes, dyslipidemia, and hypertension (both P < .05). Famine exposure during the fetal period (odds ratio 1.77, 95% confidence interval 1.22, 2.57) and childhood (odds ratio 1.82, 95% confidence interval 1.35, 2.46) was associated with an increased prevalence of moderate-severe NAFLD in women in the above fully adjusted model. CONCLUSIONS: Exposure to the Great Famine in early life had sex-specific association with moderate-severe NAFLD. This indicates that malnutrition in early life may influence the development of adult NAFLD; thus pregnant women and their infants and children may require the highest priority in obtaining nutritional relief.

Skeletal and radiological manifestations of child abuse: Implications for study in past populations.

Child abuse in its various types such as physical, emotional, sexual, and neglect has been document throughout history. However, before the mid-20th century, inflicted injuries to children was overlooked in part because children were often viewed as property. According to the World Health Organization, 57,000 children were the victims of homicide in the year 2000. In this paper we present the skeletal and radiological manifestation of physical abuse and fatal neglect and provide recommendations to assess child maltreatment from past populations. Pediatric biomechanical factors and healing are discussed as it is important to keep in mind that children are not just small adults. Skeletal and radiological indicators of nonaccidental or inflicted injuries are reviewed from the literature. Inflicted injuries are presented based on specificity to identify child abuse. In addition, skeletal indicators that could help assess fatal starvation are also reviewed and metabolic diseases are proposed as potential evidence of neglect. A recent child homicide is presented and used to illustrate the difficulty in assessing child maltreatment. Present-day clinical child abuse protocols are used to provide recommendations to assess child abuse in a bioarchaeological context. Clin. Anat. 29:844-853, 2016. © 2016 Wiley Periodicals, Inc.

Macrophage migration inhibitory factor plays a permissive role in the maintenance of cardiac contractile function under starvation through regulation of autophagy.

AIMS: The cytokine macrophage migration inhibitory factor (MIF) protects the heart through AMPK activation. Autophagy, a conserved pathway for bulk degradation of intracellular proteins and organelles, helps preserve and recycle energy and nutrients for cells to survive under starvation. This study was designed to examine the role of MIF in cardiac homeostasis and autophagy regulation following an acute starvation challenge. METHODS AND RESULTS: Wild-type (WT) and MIF knockout mice were starved for 48 h. Echocardiographic data revealed little effect of starvation on cardiac geometry, contractile and intracellular Ca²âº properties. MIF deficiency unmasked an increase in left ventricular end-systolic diameter, a drop in fractional shortening associated with cardiomyocyte contractile and intracellular Ca²âº anomalies following starvation. Interestingly, the unfavourable effect of MIF deficiency was associated with interruption of starvation-induced autophagy. Furthermore, restoration of autophagy using rapamycin partially protected against starvation-induced cardiomyocyte contractile defects. In our in vitro model of starvation, neonatal mouse cardiomyocytes from WT and MIF-/- mice and H9C2 cells were treated with serum free-glucose free DMEM for 2 h. MIF depletion dramatically attenuated starvation-induced autophagic vacuole formation in neonatal mouse cardiomyocytes and exacerbated starvation-induced cell death in H9C2 cells. CONCLUSION: In summary, these results indicate that MIF plays a permissive role in the maintenance of cardiac contractile function under starvation by regulation of autophagy.

Quantitative analysis of pulmonary pathophysiology using postmortem computed tomography with regard to the cause of death.

Radiological lung transparency depends on the air contents involved in respiratory function. The present study quantitatively investigated postmortem lung air distribution in forensic autopsy cases (n=135) using computed tomography (CT) to analyze cardiopulmonary pathophysiology in the death process, involving emphysema, congestion and edema. Combined analyses of the CT morphology and attenuation value (Hounsfield unit, HU) of the bilateral lungs, with reference to histopathology, could categorize CT findings (10-90 percentile mode/mean HU values) with regard to the causes of death as follows: (I) hyperaeration (mode/mean HU below -760/-560: emphysema) for obstructive pulmonary disease, starvation and hypothermia (cold exposure); (II) mostly normal aeration with partial ground glass opacification (mode/mean HU, -850 to -360/-700 to -380: partial congestion and edema), consisting of subtype II-a with peri-bronchial/-vascular opacity for mechanical asphyxia, drowning and fire fatality, and subtype II-b with decreased vascularity for gunshot head injury, cerebrovascular disease and hemopericardium; (III) hypoaeration to airless with predominant hypostatic ground glass opacification (mode/mean HU, -870 to 0/-720 to -200: mottled hypostatic congestion and edema) for blunt head/neck injury, intoxication, hyperthermia (heat stroke) and congestive heart failure; (IV) hypoaeration to airless with predominant hypostatic consolidation (mode/mean HU, -790 to 0/-520 to -70: intense hypostatic congestion with edema) for acute ischemic heart disease; and (V) airless to consolidated (mode/mean HU over -420/-370: segmental or multiple patchy consolidations with edema) for pneumonia. Mode HU represents the major alveolar status, while the mean HU reflects the whole lung air contents. CT data analysis is useful for quantitative evaluation of pulmonary pathology as a supplementary procedure.

[Alimentary, metabolic and toxic osteopathies in adults]. / Alimentäre, metabolische und toxische Osteopathien bei Erwachsenen.

Skeletal changes in deficient or badly balanced nutrition (alimentary osteopathies) and osseous changes accompanying chronic disease of internal organs and metabolic disorders (metabolic osteopathies) are discussed. Basically, the classical generalised skeletal changes such as osteoporosis, osteomalacia, fibroosteoclacia and sclerosis of the bone can occur in their pure form or as a combination of two ore more of these disorders. Finally the exogenic toxic osteopathies are discussed, nowadays fluorosis being the most important. Other external factors may be drugs such as methotrexate and antiepileptic medications.