Treatment improves serotonin transporter binding and reduces binge eating

Rationale Serotonin (5-HT) is involved in the control of eating behaviour by inhibiting food intake. Obese women with binge-eating disorder (OB-BED) were recently found to have reduced 5-HT transporter binding. Objectives The aim of this study was to investigate the effect of a successful treatment on 5-HT transporters in OB-BED. Methods The 5-HT transporter binding of seven OB-BED was measured by single-photon emission computed tomography (SPECT), by using iodine-123-labelled nor-β-CIT as a tracer, before treatment and after successful treatment, when the OB-BED were asymptomatic. Treatment consisted of group psychotherapy and fluoxetine medication. The control subjects, six obese women without eating disorders, were also studied twice by using SPECT. Results The 5-HT transporter binding of the symptomatically recovered OB-BED increased significantly (24±22%) after treatment, whereas in the control group, binding remained unchanged. Conclusions The results tentatively suggest that 5-HT transporter binding in OB-BED is an adaptive mechanism, which can be affected by treatment. Furthermore, there seems to be a link between improved 5-HT transporter binding and reduced binge eating.     

Transgenic mice overexpressing XIAP in neurons show better outcome after transient cerebral ischemia

X-chromosome linked inhibitor of apoptosis protein (XIAP) is a member of the inhibitor of apoptosis protein (IAP) family and known to inhibit death of various cells under different experimental conditions. Although present in brain tissue, little is known about the physiology of the IAPs in nerve cells. Here we report on the establishment of transgenic mice with overexpression of human XIAP in brain neurons. The mice developed normally, and were more resistant to brain injury caused by transient forebrain ischemia after occlusion of the middle cerebral artery compared to control mice. The XIAP transgenic animals exhibited significantly smaller brain damage, as shown by TUNEL labelling, less reduction in brain protein synthesis, and less active caspase-3 after ischemia compared with controls. Upregulation of RhoB, which is an early indicator of neurological damage, was markedly reduced in the XIAP-overexpressing mice, which had also a better neurological outcome than control animals. This together with the increase in XIAP in normal mouse brain in regions surviving the infarct demonstrates that XIAP is an important factor promoting neuronal survival after ischemia. The results suggest that interference with the levels and the activity of XIAP in neurons may provide targets for the development of drugs limiting neuronal death after ischemia, and possibly in other brain injuries.     

Spermine deficiency resulting from targeted disruption of the spermine synthase gene in embryonic stem cells leads to enhanced sensitivity to antiproliferative drugs

Polyamines are known to be essential for normal cell growth and differentiation. However, despite numerous studies, specific cellular functions of polyamines in general and individual polyamines in particular have remained only tentative, because of a lack of appropriate cell lines in which genes of polyamine-synthesizing enzymes have been disrupted by gene targeting. With the use of homologous recombination technique, we disrupted the gene encoding spermine synthase in mouse embryonic stem cells. The spermine synthase gene is located on X chromosome in mouse and, because the cells used in this study were of XY karyotype, a single targeting event was sufficient to result in null genotype. The targeted cells did not have any measurable spermine synthase activity and were totally devoid of the polyamine spermine. Spermine deficiency led to a substantial increase in spermidine content, but the total polyamine content was nearly unchanged. Despite the lack of spermine, these cells displayed a growth rate that was nearly similar to that of the parental cells and showed no overt morphological changes. However, the spermine-deficient cells were significantly more sensitive to the growth inhibition exerted by 2-difluoromethylornithine, an inhibitor of ornithine decarboxylase. Similarly, methylglyoxal bis(guanylhydrazone), an inhibitor of S-adenosylmethionine decarboxylase, and diethylnorspermine, a polyamine analog, although exerting cytostatic growth inhibition on wild-type cells, were clearly cytotoxic to the spermine-deficient cells. The spermine-deficient cells were also much more sensitive to etoposide-induced DNA damage than their wild-type counterparts.     

Transfer of absorbed cis-9, trans-11 conjugated linoleic acid into milk is biologically more efficient than endogenous synthesis from absorbed vaccenic acid in lactating cows

Cis-9, trans-11, the major isomer of conjugated linoleic acid (CLA) in bovine milk fat, is derived from ruminal biohydrogenation of 18:2 (n-6) and endogenous conversion of trans-11 18:1 (vaccenic acid; VA) in the mammary gland. Most evidence to date suggests that endogenous synthesis is the major source of cis-9, trans-11 CLA, but the extent of VA desaturation is less well defined. Four lactating cows were used in consecutive 4 x 4 Latin squares to examine changes in milk fatty acid composition and secretion in response to abomasal infusions of lipid supplements enriched with cis-9, trans-11 CLA (88.8%) or VA (29.4%). Treatments were infused over 4-d, followed by a 3-d washout, during 7 d experimental periods and administered to deliver 0, 3, 6, and 12 g cis-9, trans-11 CLA/d (Expt. 1) or 0, 7.5, 15 and 30 g VA/d (Expt. 2). Infusions of cis-9, trans-11 CLA increased linearly milk cis-9, trans-11 CLA concentrations from 0.68 to 1.46 g/100 g fatty acids. Abomasal infusions of VA increased linearly milk VA and cis-9, trans-11 CLA content from 1.22 to 2.72 and 0.61 to 1.24 g/100 g fatty acids, respectively. Changes in milk fatty acid secretion indicated that 28.9% of VA was converted to cis-9, trans-11 CLA. Results provide evidence that conversion by Delta9-desaturase to cis-9, trans-11 CLA in the lactating cow is independent of postruminal VA supply. In conclusion, endogenous synthesis via VA was equivalent to approximately 21% of the response to increases in cis-9, trans-11 CLA available for absorption.     

Comparison of different sampling techniques and of different culture methods for detection of group B streptococcus carriage in pregnant women

Background  

Streptococcus agalactiae (group B streptococcus; GBS) is a significant cause of perinatal and neonatal infections worldwide. To detect GBS colonization in pregnant women, the CDC recommends isolation of the bacterium from vaginal and anorectal swab samples by growth in a selective enrichment medium, such as Lim broth (Todd-Hewitt broth supplemented with selective antibiotics), followed by subculture on sheep blood agar. However, this procedure may require 48 h to complete. We compared different sampling and culture techniques for the detection of GBS.     

The effect of nitecapone, a new antioxidant, on myocardial function after aortic cross-clamping in experimental heart ischemia

During aortic cross-clamping, the myocardium suffers from global ischemia, which is followed by reperfusion after declamping. The generation of free oxygen radicals increases during reperfusion, resulting in arrhythmias and impaired cardiac function. This study was conducted to evaluate the effect of a novel antioxidant nitecapone (NC) on cardiac reperfusion injuryin vivo. Twelve pigs were anesthetized and after sternotomy the aorta and the right atrium were cannulated for cardiopulmonary bypass. The heart was arrested with either +4°C crystalloid cardioplegia alone in the control group (n=6) or cardioplegia with NC (50 µM) added in the NC group (n=6). Cardioplegia was added every 20 minutes. After 1 hour of aortic crossclamping, blood samples for oxidative stress analysis were taken, and hemodynamic profile surveillance continued for 90 minutes. Heart rate (p=0.04) and left ventricular end diastolic pressure (LVEDP) (p=0.04) were significantly lower in the NC group than in the C group after aortic declamping. Cardiac output and myocardial contractility (dP/dt_max) were also enhanced in the group receiving NC, but the difference was not statistically significant. At 30 minutes after reperfusion, the coronary production (coronary sinus-aorta) of thiobarbituric acid reactive substances correlated inversely with cardiac output (r=–0.90,p=0.001) and stroke volume (r=–0.82,p=0.007). The effect of NC on lipid peroxidation seems to be modest and therefore the target of NC is unclear. NC would appear, however, to be a beneficial additive in the crystalloid cardioplegia in terms of functional recovery.     

A multicentred clinical improvement project among preterm population evaluation of current practices

Sepsis, a potentially life-threatening infection, is a common complication related to the use of central venous catheters (CVCs) in the preterm infant population. Best practice guidelines include successful strategies to prevent infections. Central venous catheter use is a fairly recent intervention in Finnish neonatal intensive care units (NICUs). As part of a quality improvement project to evaluate catheter-related care practices, 4 NICUs collaborated in a multicenter, multiprofessional study aimed at decreasing the incidence of catheter-related sepsis among a population of preterm infants. This article describes the initial phase that evaluated current protocols and practices. The findings were that current protocols need revision to include more detailed and accurately focused instructions on infection prevention associated with CVC. Many challenges in performing certain procedures with catheters were found. Precis CVC protocols and practices in 4 Finnish NICUs were reviewed for infection control measures.     

Wheezing due to rhinovirus infection in infancy: Bronchial hyperresponsiveness at school age

Background: Characteristics related to decreased lung function and increased bronchial responsiveness after early childhood wheezing requiring hospitalization are not fully established.
Methods: Seventy-nine children with wheezing requiring hospitalization at age <2 years were prospectively followed up and re-investigated at age 5.6–8.8 years when the measurements of baseline lung function and bronchial responsiveness to exercise were performed.
Results: At early school age, 23% of children had decreased lung function, and 13% had increased bronchial responsiveness to exercise. Predictors of decreased lung function were maternal history of smoking during pregnancy (odds ratio [OR], 12.8; 95% confidence interval [CI]: 1.2–139.6), parental history of asthma (OR, 4.3; 95%CI: 1.1–17.1), and female gender (OR, 4.0; 95%CI: 1.2–13.7). Increased bronchial responsiveness was associated with rhinovirus infection-induced wheezing in infancy (OR, 6.5; 95%CI: 1.2–36.3), and early cat or dog exposure leading to sensitization (OR, 26.6; 95%CI: 1.3–525.2). Inhaled anti-inflammatory therapy was common in children with rhinovirus infection-induced wheezing in infancy ( n  = 13/19; P  = 0.001 vs children with other/no confirmed virus infection etiology for wheezing in infancy, n  = 16/60), which may have improved lung function and attenuated bronchial responsiveness in them.
Conclusions: After early childhood wheezing requiring hospitalization, one-fourth of children will have decreased lung function and one-eighth of children will show increased bronchial responsiveness at school age. Gender, heredity of asthma, and antenatal exposure to tobacco smoke are predictors of decreased lung function, whereas rhinovirus infection etiology of wheeze and early animal exposure leading to sensitization are associated with increased bronchial responsiveness later in childhood.