Association of BDNF with anorexia, bulimia and age of onset of weight loss in six European populations

Several genes with an essential role in the regulation of eating behavior and body weight are considered candidates involved in the etiology of eating disorders (ED), but no relevant susceptibility genes with a major effect on anorexia nervosa (AN) or bulimia nervosa (BN) have been identified. Brain-derived neurotrophic factor (BDNF) has been implicated in the regulation of food intake and body weight in rodents. We previously reported a strong association of the Met66 allele of the Val66Met BDNF variant with restricting AN (ANR) and low minimum body mass index in Spanish patients. Another single nucleotide polymorphism located in the promoter region of the BDNF gene (-270C>T) showed lack of association with any ED phenotype. In order to replicate these findings in a larger sample, we performed a case-control study in 1142 Caucasian patients with ED consecutively recruited in six different centers from five European countries (France, Germany, Italy, Spain and UK) participating in the 'Factors in Healthy Eating' project. We have found that the Met66 variant is strongly associated to all ED subtypes (AN, ANR, binge-eating/purging AN and BN), and that the -270C BDNF variant has an effect on BN and late age at onset of weight loss. These are the first two variants associated with the pathophysiology of ED in different populations and support a role for BDNF in the susceptibility to aberrant eating behaviors.     

Number of interleukin-4- and interferon-γ-secreting human T cells reactive with tetanus toxoid and the mycobacterial antigen PPD or phytohemagglutinin: distinct response profiles depending on the type of antigen used for activation

The enzyme-linked immunospot (ELISPOT) assay has been proven to be an efficient and sensitive method for the enumeration of single cells secreting antibodies or cytokines. Here we have used this method to determine the number of interleukin-4 (IL-4)- and interferon-γ (IFN-γ)-producing cells in in vitro secondary responses to tetanus toxoid (TT) and the mycobacterial antigen (purified protein derivative; PPD) or the mitogen phytohemagglutinin (PHA). PHA-induced IL-4 and IFN-γ secretion was well correlated suggesting polyclonal activation of cells. This was not the case with the specific antigens, where PPD preferentially induced IFN-γ- and very few IL-4-producing cells, while TT-induced both IL-4 and IFN-γ. These differences are probably a reflection of the types of immunity the two antigens induce, mycobacteria preferentially inducing a cell-mediated T helper type 1 (Th 1) type of immunity, while immunity to tetanus is an antibody-dependent, Th 2 type of response. In individuals recently boosted with TT, a significant increase in both IL-4- and IFN-γ-producing cells in response to TT was seen at day 7 after boost, followed by decline. This was in contrast to what was seen in response to PPD where an increase of IFN-γ-producing cells after the TT boost at day 7 persisted for at least 14 days. These results suggest that after an in vivo boost both antigen-specific and nonspecific T cells are activated and that antigen-specific cells home to other organs and therefore may be difficult to demonstrate in the circulation. Our data show that the ELISPOT assay is a powerful tool for determining the frequency of cells secreting cytokines. The assay has several advantages over other assays since it is sensitive, measures the number of actually secreting cells, and avoids the problems of binding of cytokines to their cell-bound or soluble receptors.     

Effect of training on hormonal responses to exercise in competitive swimmers

Summary The effects of 9 weeks of training on responses of plasma hormones to swimming were studied in eight competitive swimmers who had not trained for several months. Two types of swimming tests were used: (1) 200 yd, a high intensity, exhausting type of exercise in which maximal effort was required both before and after training, and (2) 1000 yd, a pace type of exercise in which subjects swam as fast as possible prior to training and at the same rate after training. Plasma levels of glucagon increased and of insulin decreased during 1000 yd of swimming, but were not altered by 200 yd of swimming. No training effects were apparent in responses of plasma insulin and glucagon to these short-term, high intensity exercise tests. During the 1000 yd swim, plasma adrenaline was 0.8 ng/ml before vs. 0.1 ng/ml after training. Plasma noradrenaline response decreased from 3.4 to 1.2 ng/ml as a result of training. In the 200 yd swim, adrenaline, but not noradrenaline, was lower after training.R. C. Hickson and R. K. Conlee were postdoctoral research trainees supported by NIH Training Grant AM-05341.J. M. Hagberg was a postdoctoral research trainee supported by NIH Training Grant HL-07081.     

Human gender differences in fibrinolytic responses to exercise training and their determinants

Endurance exercise training improves fibrinolysis, but this training-induced adaptation may differ somewhat between men and women. We sought to determine whether the potential gender differences in training-induced changes in selected fibrinolysis measures were related to changes in adiposity and/or plasma lipoprotein lipid levels. Seventeen men and 28 women, 50-75 years old, who were generally overweight to obese, were assessed for plasminogen activator inhibitor-1 (PAI-1) and tissue plasminogen activator (t-PA) activity, t-PA antigen and plasma lipoprotein-lipid levels, and body composition before and after 6 months of endurance exercise training while on a low-fat diet. At baseline, there were no differences in fibrinolytic measures between the men and women. Baseline levels of these fibrinolytic markers in both men and women were primarily related to other fibrinolytic measures and body composition, with a smaller contribution from plasma high-density lipoprotein cholesterol (HDL-C) levels. Exercise training reduced t-PA antigen levels in both men and women, but the reduction was significantly greater in men (-1.6 +/- 0.3 versus -0.5 +/- 0.2 ng ml(-1), P = 0.007). Exercise training decreased PAI-1 activity more in men than in women (-2.6 +/- 1.4 versus +0.9 +/- 0.9 IU ml(-1), P = 0.03). Men and women both showed increased t-PA activity with exercise training to the same extent (+0.38 +/- 0.12 versus +0.36 +/- 0.24 U ml(-1)). The changes in fibrinolytic measures with exercise training in men and women were correlated with changes in other fibrinolytic measures, although in men abdominal fat changes were a strong predictor of fibrinolytic changes with training. These findings suggest that training-induced improvements in endogenous fibrinolysis markers are somewhat greater in men compared to women and may be more strongly associated with abdominal obesity in men.     

Changes in the surface electromyogram during increasing isometric shoulder forward flexions

Summary When using electromyographic techniques in the evaluation of muscular load it is necessary to determine the mathematical relationship between the torque and the amplitude of the electromyographic signal. Isometric gradually increasing contractions up to 100% MVC can then be used. Often more than linear increases for the amplitude (RMS) — force regression have been reported. The present study was designed to test whether changes in power spectral density function take place during a gradually increasing isometric contraction (duration 10 s). Twenty-two clinically healthy females performed an increasing isometric shoulder forward flexion for 10 s using an isokinetic dynamometer. Electromyographic activity was measured in trapezius, deltoid, infraspinatus and biceps brachii using surface electrodes. Mean torque values were determined together with mean power frequency (MPF) and root mean square values (RMS) from the EMG signals for each 256 ms period. The RMS-torque regressions showed higher regression coefficients during the 6th to 9th sec than during the first 5 s. No significant correlation existed between MPF for the four muscles and the torque. A gradual decrease in MPF was generally found from the 6th s. It is concluded that this decrease in power spectral density function might have contributed to the significantly higher regression coefficient for the RMS torque regression at the high output part of the gradually increasing isometric contraction.     

Influence of tissue lactic acid and ATP levels on postischemic recovery in rabbit skeletal muscle

The effect of energy substrate depletion and of high lactic acid (LA) load on the development of irreversible cell injury was evaluated in the lateral gastrocnemius muscle of rabbits subjected to 4 hr of tourniquet hindlimb ischemia. Three groups of animals were studied. Group I, high ATP-ischemia, these animals were subjected to 4 hr of ischemia; group II, low ATP--low LA ischemia, in this group the gastrocnemius muscle was electrically stimulated for 5 min during ischemic conditions to reduce the glycogen store, a short reperfusion period was allowed after the stimulation in order to wash out the built up LA, and the muscle was then subjected to 4 hr of ischemia; group III, low ATP--high LA ischemia, in this group glycogen was depleted as in group II, but no reperfusion period was allowed before the 4 hr period of ischemia. In group I, ATP levels were well preserved during the ischemic period, whereas in the substrate-deprived groups (II and III) a rapid depletion of ATP and phosphocreatine (CP) occurred. The LA was twice as high in the "high LA" group (III) as in the "low LA" group (II) during the ischemic period. The extent of injury was evaluated after 24 hr of reperfusion by measuring ATP and CP content, and contractile force and by light microscopy. No or minor cell damage was found in group I. In group III--high LA--no recovery was obtained in any of the variables used for evaluation. In group II--Low LA--there was a certain recovery. ATP and CP increased to about 35% and contractile force to 25% of control. Morphologically about 20% of the muscle cells appeared to be unaffected by the ischemic insult. It is concluded that reduction of the glycogen available for ATP resynthesis during the ischemic period drastically reduces the ability of skeletal muscle to withstand prolonged ischemia. A high LA load seems to amplify the deleterious effects of a low initial substrate level.     

Musculoskeletal symptoms and job strain among nursing personnel: a study over a three year period.

OBJECTIVES: To examine the variation of symptoms from the neck, shoulders, and back over a three year period among female nursing personnel and the relation between job strain and musculoskeletal symptoms. METHODS: At a county hospital the female nursing personnel answered a questionnaire at baseline and then once a year over a period of three years. There were 565, 553, 562, and 419 subjects who answered the questionnaire at the first, second, third, and fourth survey, respectively. Of the study group, 285 nursing personnel answered the questionnaire on four occasions. Ongoing symptoms of the neck, shoulders, and back were assessed by means of a 10 point (0-9) scale with the verbal end points "no symptoms" and "very intense symptoms." Cases were defined as nursing personnel reporting ongoing symptoms, score > 6, from at least one of the body regions. For assessments of job strain, a Swedish version of Karasek and Theorell's model was used. RESULTS: Of the 285 subjects, 13% were defined as cases at all four assessments, and 46% varied between cases and not cases during the study period. In the repeated cross sectional surveys the estimated rate ratio (RR) for being a case was between 1.1 and 1.5 when comparing the group with job strain and the group without job strain. For the combination of job strain and perceived high physical exertion the estimated RR was between 1.5 and 2.1. When the potential risk factors were assessed one, two, or three years before the assessment of symptoms the estimated RR for becoming a case was between 1.4 and 2.2 when comparing the group with job strain and the group without job strain. CONCLUSION: Almost half of the healthcare workers varied between being a case and not, over a three year period. The analysis indicated that job strain is a risk factor for musculoskeletal symptoms and that the risk is higher when it is combined with perceived high physical exertion.     

Rett syndrome, classical and atypical: genealogical support for common origin.

AIMS OF THE STUDY: By using genealogical methods in atypical females with Rett syndrome (RS) we looked for support for the assumption that atypical RS cases are true variants of classical RS. SUBJECTS: We selected from the Swedish national RS series the "milder" RS cases, 10 years of age and older, fulfilling the criteria for the "forme fruste" (FF) type of RS. For 32 FF cases we were able to carry out complete genealogical analyses on 61 parental lines. The pedigrees contained details of about 3200 ancestors. COMMON GEOGRAPHICAL ORIGINS: Eleven (34%) of the FF females could be traced to a previously defined "Rett area" and no fewer than six females had their origin in the same homestead as another previously examined classical RS patient. ANCESTRY: In four pedigrees, two each contained one FF and two classical RS and two each contained one FF and one classical RS, all 10 being descendants of the same four couples who lived several generations ago. CONSANGUINITY: Consanguinity in four grandparents (6.6% (SD 3.2%)) is probably a higher frequency than in the average Swedish population and supported our findings from a series of classical RS. TRANSMISSION: The data indicate that transmission starts with a premutation that over generations can result in a full mutation giving rise to RS. Both the X chromosomes and a pair of autosomes may be involved. CONCLUSION: Many, or most, atypical FF cases are true variants of RS.     

General musculoskeletal complaints in a group of patients with craniomandibular disorders (CMD). A case control study

In a cross sectional study 30 patients with craniomandibular disorders (CMD) and 30 controls were screened for general musculoskeletal complaints. A questionnaire was used to mark the sites of the body that were painful and assessments of pain intensities in the neck, shoulders and the jaws were registered. "Pain tolerance" was clinically measured with cutaneous electrical stimulation over the masseter areas. The CMD patients had a significantly higher number of painful sites on the body than the controls. They showed significantly increased "relative risks" of having musculoskeletal pain especially in the upper neck, the shoulder and lower neck region, the shoulder joint and the thoracic back. Discomfort and pain rating values for the neck and shoulders were significantly higher for CMD patients than for controls. The measurements of "pain tolerance" did not differ between groups. However, an individual variation was found among the CMD patients. Those who had pain in many different parts of the body were the least tolerant of experimentally induced pain.