Fibroblast growth factor 21 (FGF21) and bone: is there a relationship in humans?

UNLABELLED: In animals, high fibroblast growth factor 21 (FGF21) states improve insulin resistance but induce bone loss. Whether FGF21 relates to bone mineral density (BMD) is unknown in humans. Contrary to prediction from animal findings, we found higher FGF21 levels associating with greater BMD in women, independent of age and body composition. INTRODUCTION: Recent laboratory studies suggest that FGF21 is involved in reciprocal regulation of bone and energy homeostasis. Systemic administration of FGF21 protects animals from obesity and diabetes but causes severe bone loss, smothering the enthusiasm over FGF21 as a potential antiobesity therapeutic. To date, there is no information on whether FGF21 relates to BMD in humans. We thus studied the relationship between plasma FGF21 levels and BMD in healthy adults. METHODS: Fasting plasma FGF21 levels were measured by enzyme-linked immunosorbent assay and body composition by dual-energy X-ray absorptiometry. RESULTS: Among 40 healthy volunteers (age 32 ± 10 year, 16 women), men had significantly higher lean body mass (p < 0.01) and total BMD (p < 0.05), and lower percent body fat than women (p < 0.01). Median plasma FGF21 levels were not different between the sexes. While there was no association between FGF21 concentrations and body composition in men, FGF21 levels correlated positively with fat mass (p < 0.01) in women. In men, no significant correlation between FGF21 with BMD was observed. However, in women, FGF21 correlated positively with total BMD (R (2) = 0.69, p = 0.003) and spine BMD (R (2) = 0.76, p = 0.001); the correlation remained significant after adjusting for age, ethnicity, and body composition. CONCLUSIONS: This study reveals for the first time a strong positive association between plasma FGF21 levels and BMD in healthy women, suggesting the association between bone loss and high FGF21 states in animals may not be directly translated to humans in physiologic states. We hypothesize that FGF21 may increase bone mass particularly in women through paracrine mechanisms in the bone-adipose interface.

Delta9 -tetrahydrocannabinol increases brain temperature and inverts circadian rhythms.

Delta9-tetrahydrocannabinol (THC) has been shown to protect against focal and global ischemia. Hypothermia is thought to be one mechanism for this protection. These observations are important since brain hyperthermia is known to increase ischemic damage while hypothermia is protective. To establish the effect of THC on brain and body core temperature, brain and body temperature probes were inserted for chronic temperature monitoring (n = 20). THC treated groups were administered THC at either low (0.1 mg/kg) or high (10 mg/kg) dose for 1 week. Brain temperature was recorded during this period and for 1 week following the discontinuation of THC. Chronic administration of THC at either dose increased brain temperature (p < 0.0001) but did not significantly change body core temperature (p = 0.4767) in the freely moving rat.

Impact of routine use of intraoperative transesophageal echocardiography during cardiac surgery.

PURPOSE: To determine the relative impact of each category-based TEE indication according to the ASA guidelines. METHODS: In 851 patients undergoing cardiac surgery, TEE clinical indications were classified as category I or II according to the ASA guidelines. Category I indications are patients in which TEE is considered useful and category II are those where TEE is potentially useful but indications are less clear. All TEE examinations were reviewed by two anesthesiologists with advanced training in TEE. For each patient, the clinical impact of TEE in the clinical management was assessed using five criteria: 1) change of medical therapy; 2) change in the surgical procedure; 3) confirmation of a suspected diagnosis; 4) positioning of an intravascular device, and 5) substitute to a pulmonary artery catheter (PAC). RESULTS: TEE had greater utility in category I than in category II indications (15/53 (28%) vs. 110/798 (14%) respectively) (P<0.01). The nature of the clinical impact was as follows: modification of medical therapy in 67/125 (53%), modification of planned surgical intervention in 38/125 (30%), confirmation of a diagnosis in 34/125 (27%). The impact on therapy was higher in complex surgical procedures (39%) than in valvular replacement (19%) (P<0.01) and coronary artery bypass surgery (10%) (P<0.001). CONCLUSIONS: Our findings validate the usefulness of the ASA practice guidelines demonstrating a greater impact of TEE on clinical management for category I indications than for category II. TEE also had a greater clinical impact in complex surgical procedures and in valvular replacement.

[Yew poisoning in Australian emus (Dromaius novaehollandiae, LATHAM)]. / Eibenvergiftung bei australischen Emus (Dromaius novaehollandiae, LATHAM).

Six, four month old, captive bred emus (Dromaius novaehollandiae) were found dead in their pen without any previous indications of illness. Postmortem examination revealed the cause of death to be taxine poisoning after ingestion of leaves and green berries from a Yew bush (Taxus baccata) growing outside the perimeter fencing but encroaching through the wire. After longstanding access to the Yew bush, an unidentified stimulus prompted these young birds to sample this toxic plant. Pathological findings included changes in the lungs, heart, liver, spleen and most parts of the digestive system as would be expected from the quoted sources concerning taxine poisoning in other species. Considering the varied artificial environments in which taxa are kept and the relative infrequency of autopsies carried out on birds, the incidence of taxine poisoning in avian species is considered to be probably much higher than that evidenced by reference to the published literature.

Effects of infectious bovine rhinotracheitis virus infection on bovine airway reactivity.

The response of isolated tracheal and bronchial strips to isoproterenol in vitro was studied in eleven male Jersey calves. Clinical, microbiological and pathological evaluations of the calves were carried out. In calves exposed once or twice to infectious bovine rhinotracheitis virus, the relaxation threshold of the trachealis muscle to isoproterenol was significantly (p less than 0.05) impaired (threshold 5.0 X 10(-7) M, single exposure and 1.0 X 10(-7) M, double exposure), when compared with uninfected controls (threshold 1.0 X 10(-8) M). Single infection significantly impaired tracheal relaxation to isoproterenol doses from 1.0 X 10(-7) to 5.0 X 10(-4) M, and double infection significantly impaired tissue responses at drug doses from 1.0 X 10(-7) to 1 X 10(-4) M. Bronchial relaxation threshold was not significantly inhibited (p less than 0.05) in singly infected or doubly infected animals (threshold 5.0 X 10(-8) M and 1.0 X 10(-8) M, respectively), when compared with uninfected controls (threshold 1.0 X 10(-9) M). Single infection significantly impaired bronchial relaxation at isoproterenol doses from 1.0 X 10(-7) M to 5.0 X 10(-6) M while double infection significantly impaired relaxation only at 5.0 X 10(-7) M. The disruption of normal homeostatic bronchodilatory mechanisms may predispose animals infected with infectious bovine rhinotracheitis virus to secondary bacterial infections due to excessive airway constriction and subsequent compromise of lung defenses.

Characterization of the beta receptor responsible for enhanced histamine release from bovine leukocytes.

The present study was undertaken to determine the beta-receptor subtype responsible for the enhanced anaphylactic histamine release from bovine leukocytes produced by isoprenaline. The selective beta 1 antagonist practolol competitively inhibited the enhancement of histamine release produced by isoprenaline. The selective beta 2 agonists salbutamol and terbutaline produce no significant effect on antigen-induced histamine release. This indicates that the receptor responsible for enhancement of histamine release from bovine granulocytes is of the beta 1 subtype. The question is raised as to whether this is a normal physiological response or an abnormal condition produced by the sensitization procedure.

Effect of synthetic cyclic nucleotides on immunologic histamine release from calf granulocytes.

Sensitized bovine granulocytes release histamine when exposed to specific antigens. A unique modulation of histamine release by adrenergic agents has been shown in the bovine; beta-adrenergic agonists enhance and alpha-adrenergic agonists inhibit histamine release. This is an opposite response to that reported in other species. The present study was undertaken to determine the possible relationship between cyclic nucleotides and adrenergic agents in this species. Dibutyryl cAMP enhanced antigen-induced histamine release over the complete concentration range tested (10(-6)--10(-3)M); it also overcame, in a dose-dependent manner, the inhibition of antigen-induced histamine release produced by 10(-4) M phenylephrine. The 8-bromo cGMP AND 0-MONOBUTYRYL CGMP had no significant effect on antigen-induced histamine release nor did 8-bromo-cGMP have any significant effect on the enhancement of histamine release produced by 10(-4) M dibutyryl cAMP. These findings suggest that only cAMP has a role in the modulation of antigen-induced histamine release from bovine granulocytes.

[The concept of mental deficiency. Evolution of theories, attitudes and practices]. / Le concept de déficience mentale. Evolution des théories, des attitudes et des pratiques.

In the last twenty years a deep renewal of the conceptions about and the treatments of the mentally deficients has taken place. In an attempt to clarify somehow the confusion in the communication between specialists, the author reminds the classical position on this subject, which relies upon the definition of the idiocy: a state of a severe mental defect, set up early in life, with an organic cause and being incurable for this reason. In spite of the later considerable differenciation at different levels and types, the classical position maintains this definition as the ground of the nosographic class of the mental retardations (debility is considered then as a light idiocy), divided in two sub-classes of either "polygenic heredity" or accidents causing early brain damages. From a clinical point of view, such a theoretical position is difficult to apply, especially in cases of middle and light mental defects. From a theoretical point of view, this classical position has been often attacked: by the evidence of the socio-cultural factors of the intellectual development, by the analysis of the so-called instrumental troubles, by the studies about the early lack of mother-care and the child-psychoses with a defect, by the more recent works on dysharmonic evolvements, etc. All this has lead to major theoretical changes which force to give up the illusion of a "single class" of mental retardations and study therefore each case in the trajectory of its development, not only of the cognitive patterns but also of the whole personality structure. This clinical approach forces to admit organic, environmental (sociological and psycho-sociological) and relational, dynamic factors as well; and, to accept that their combination, replaced in a genetic context of the functioning patterns, establishes a new, properly psychological level of causality. So, even the idea of a "defectology" is non-sense; the factors and the problems in question are the same as in any other psychogenesis. Nevertheless, the study of cases, in which this psychogenesis is caracterized by a mental deficit, is very important.