Prediction of body composition in anorexia nervosa: Results from a retrospective study

Summary Background & aims The assessment of body composition is crucial in evaluating nutritional status in female subjects with anorexia nervosa (AN) and improving their clinical management. The aim of this retrospective study was to assess the accuracy of selected BIA (bioimpedance analysis) equations for fat-free mass (FFM) in female AN subjects and to formulate a specific equation for these subjects. Methods Eighty-two restrictive female AN subjects (age 20.5 ± 3.7 yrs, BMI 15.7 ± 1.7 kg/m 2 ) were studied. Body composition was determined with dual-energy X-ray absorptiometry (DXA) and estimated by BIA using five different equations. Linear correlation analysis was carried out to evaluate the association of FFM with selected variables. Multiple regression analysis was used to formulate specific equations to predict FFM in AN. Results All predictive equations underestimated FFM at the population level with a bias from −5.6 to −11.7%, while the percentage of accurate predictions varied from 12.2% to 35.4%. More interestingly, multiple regression analysis clearly indicates that, in addition to weight, ZI 100 or RI also emerged as independent predictors of DXA-derived FFM, increasing the prediction power of the equation well above that observed with anthropometric characteristics only. Conclusions This study shows that the selected predictive BIA equations considered exhibit an insufficient accuracy at the population and the individual level. Predictive formulas based on body weight plus BIA parameters such as RI and ZI 100 offer a rather accurate prediction of FFM (with high R squared)

Inflammation and Epstein-Barr Virus Infection Are Common Features of Myasthenia Gravis Thymus: Possible Roles in Pathogenesis

The thymus plays a major role in myasthenia gravis (MG). Our recent finding of a persistent Epstein-Barr (EBV) virus infection in some MG thymuses, combined with data showing that the thymus is in a proinflammatory state in most patients, supports a viral contribution to the pathogenesis of MG. Aim of this study was to gain further evidence for intrathymic chronic inflammation and EBV infection in MG patients. Transcriptional profiling by low density array and real-time PCR showed overexpression of genes involved in inflammatory and immune response in MG thymuses. Real-time PCR for EBV genome, latent (EBER1, EBNA1, LMP1) and lytic (BZLF1) transcripts, and immunohistochemistry for LMP1 and BZLF1 proteins confirmed an active intrathymic EBV infection, further supporting the hypothesis that EBV might contribute to onset or perpetuation of the autoimmune response in MG. Altogether, our results support a role of inflammation and EBV infection as pathogenic features of MG thymus

The two-process theory of face processing: modifications based on two decades of data from infants and adults

Johnson and Morton (1991) used Gabriel Horn’s work on the filial imprinting model to inspire a two-process theory of the development of face processing in humans. In this paper we review evidence accrued over the past two decades from infants and adults, and from other primates, that informs this two-process model. While work with newborns and infants has been broadly consistent with predictions from the model, further refinements and questions have been raised. With regard to adults, we discuss more recent evidence on the extension of the model to eye contact detection, and to subcortical face processing, reviewing functional imaging and patient studies. We conclude with discussion of outstanding caveats and future directions of research in this field

Guanosine prevents nuclear factor-\u3baB nuclear translocation ameliorating experimental colitis in rats

Background inflammatory bowel diseases (IBDs), including Crohn\u2019s disease (CD) and ulcerative colitis (UC), are prevalent and debilitating health problems worldwide. Due to the adverse effects of classical treatment for IBD, therapeutic options and approaches for these diseases continue to evolve. Guanosine, a guanine-based purine, is an extracellular signalling molecule that seems to exert anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. The aim of the present study was to investigate whether exogenous guanosine may have protective effects on 2,4-dinitrobenzene sulfonic acid (DNBS)-induced Colitis in rat. Methods Experimental Colitis was induced by intrarectal administration of 0.25 ml of DNBS in 50% EtOH solution. After the induction of colitis animal received daily for 6 consecutive days i.p injection of guanosine (8 mg/kg). The effects of guanosine on DNBS-induced colitis were assessed by determination of body weight loss, stool consistency, colon weight/length, histological analysis, Furthermore the myeloperoxidase activity was biochemically evaluated and the mRNA expression of pro-inflammatory cytokines was detected by real-time quantitative reverse transcription PCR (qRT-PCR). In addition, nuclear factor-\u3baB (NF-\u3baB) p65 protein expression levels in colon tissues was investigated using Western blotting and markers of oxidative and nitrosative stress were detected. Results Inflammation in DNBS-rat is characterised by symptoms of losing body weight, loose feces/watery diarrhoea, leukocyte infiltration upregulation of proinflammatory cytokines, oxidative and nitrosative stress. Treatment with guanosine (8 mg/kg) significantly ameliorated the severity of DNBS-induced colitis as evidenced by the reduction in body weight loss and in diarrhoea. Guanosine also prevented the macroscopic and microscopic damage to the colonic mucosa, and the increase in myeloperoxidase activity induced by DNBS. Furthermore, the guanosine treated colitis rats also exhibited a lower mRNA level of pro-inflammatory cytokines, namely interleukin-1\u3b2 , interleukin-6 and tumour necrosis factor-\u3b1. Importantly, the ameliorative effect of guanosine was related to an inhibition of the NF-\u3baB signalling pathway by downregulating the expression levels of NF-\u3baB p-65, and to a reduction of DNBS increased levels of reactive oxygen species and nitrite. Conclusion Overall these results indicate that guanosine is able to alleviate colonic inflammation in DNBS- rats mainly by down-regulation of the NF-\u3baB signalling pathway and of the production of anti-inflammatory cytokines, reactive oxygen species and nitrite. Further studies are encouraging for disclosure guanosine as a novel drug candidate for the treatment of colonic inflammation

ROLE OF RENIN-ANGIOTENSIN SYSTEM IN COLONIC DYSMOTILITY ASSOCIATED WITH BOWEL INFLAMMATION IN RATS

Dysregulation of different mediator systems could contribute to the gut dismotility in inflammatory bowel diseases (IBDs), chronic disorders characterized by an exasperated immune response disturbing gut functions. Among these, Angiotensin II (Ang II), the main peptide of renin-angiotensin system (RAS), can participate in inflammatory responses and RAS components are increased in IBD patients. Since RAS has emerged as gut motility regulator, our objectives was to investigate, in an IBD rat model, the RAS functionality and its eventual contribution to colonic dismotility. Experimental colitis was induced in rats by intracolonic administration of 2,4-dinitrobenzenesulfonic acid (DNBS). Drug effects on the longitudinal colonic muscular contractility of normal and DNBS-treated rats were characterised in vitro, using organ bath-technique. Colonic preparations from DNBS rats, showed a low in amplitude spontaneous activity and a depressed responsiveness to pharmacological agents, such as the cholinergic agonist, carbachol and the β- adrenergic receptor agonist isoproterenol, compared to normal rats. Ang II induced muscular contraction in normal and inflammatory conditions, whose amplitude was decreased in DNBS rats. In both preparations the AT1 receptor antagonist, losartan, reduced Ang II effects. The AT2 receptor antagonist, PD123319, ineffective in control rats, enhanced Ang II contractile responses in DNBS rats. The neural toxin, TTX and L-NNA, NO synthase inhibitor, were ineffective in control rats, but increased contractile response in DNBS rats. The joint application of PD123319 and TTX or L-NNA did not have additive effects. Interestingly, PD123319 improved the spontaneous activity and carbachol and isoproterenol responses in DNBS animals. In conclusion, Ang II contracts rat colonic longitudinal muscle via post-junctional AT1 receptors. Under bowel inflammation AT2 receptor recruitment, likely on inhibitory nitrergic neurons, decreases colonic contractility and would counteract AT1 activity. Pharmacological manipulation of RAS system could be considered in the attempt to improve the treatment of intestinal dismotility in IBDs

Differential recruitment of Angiotensin II receptors in the modulation of rat colonic contractile activity in experimental inflammation

Objective: Inflammatory Bowel Diseases (IBD), are severe gastrointestinal (GI) disorders, with unknown aetiology, characterized by a chronic intestinal inflammatory reaction, progressively affecting GI functions, as gut motility. During inflammatory events, modifications in the functionality of some enteric modulators could contribute to the pathological changes of GI motor patterns. Angiotensin II (Ang II), the main effector of the renin-angiotensin system (RAS), has been recently reported as novel regulator of GI motility, acting on the specific receptors (AT1R and AT2R) located on the gut wall. Since recent studies have pointed out an involvement of RAS system in GI inflammation, we explored the RAS functionality and its eventual contribution to colonic dismotility in a rat model of IBD. Methods: Colitis was induced in rats by intrarectal administration of 2,4-Dinitrobenzene sulfonic acid (DNBS). Colonic damage was assessed by disease activity index (DAI), macroscopic and microscopic scores, myeloperoxidase activity (MPO) and TNF- tissue levels on day 6 after induction of colitis. Effects of Ang II on the contractility of colonic longitudinal muscle strips was recorded isometrically. Effect of 6- day intraperitoneal treatment with PD123319 (3 mg/kg) on amelioration of colitis induced by DNBS was examined in separate group of animals. Results: Colonic strips from IBD rats presented, compared to control preparations, an altered spontaneous activity, characterised by lower in amplitude contractions, and reduced sensitivity to carbachol (CCh), a muscarinic cholinergic receptor agonist, and to Isoproterenol (Iso), adrenergic receptor agonist. Ang II induced a concentration-dependent muscular contraction in both preparation, which was decreased with a rightward shift of the concentration–response curve in IBD animals. Ang II-evoked contraction was reduced, in both preparations, by Losartan, AT1R antagonist. PD123319, AT2R antagonist, caused a significant enhancement of Ang II response only in inflamed tissues. PD123319 effects were mimicked by L-NNA, nitric oxide synthase inhibitor, and by TTX, neural blocker,. The joint application of PD123319 and L-NNA or PD123319 and TTX had no additive effects. Indeed, in IBD preparations, PD 123319 per se ameliorated the mechanical activity increasing both the spontaneous contractions and the sensitivity to CCh and Iso. Daily PD123319 treatment ameliorated the severity of colitis, specially reducing DAI and improving mechanical activity. Conclusions: Ang II contracts longitudinal muscle of rat colon via activation of postjunctional AT1R. During inflammation, tonic activation of AT2R, coupled to the nitrergic signalling, counteract AT1 excitatory effects and would contribute to the reduction of muscle contractility. Pharmacological manipulation of the RAS system seems to improve some IBD symptoms and could provide a future therapeutic strategy for treatment of IBD-associated intestinal dismotility

MATERNAL HIGH FAT DIET CONSUMPTION DURING PREGNANCY AND LACTATION: IMPACT ON INTESTINAL MORPHOLOGY AND FUNCTION IN PREWEANING OFFSPRING

Different evidence supports an important role for maternal obesity in the development of childhood obesity and subsequent adult disease. This study is addressed to investigate if and to which extend maternal high fat feeding would induce compensatory and adaptative responses in gut predisposing to the eventual development of paediatric obesity. Adult female mice were divided into two groups fed with i) high fat (HF) diet and ii) standard chow (SC)diet, during pregnancy and lactation. HF mothers showed a significant weight gain, higher levels of blood glucose and an abnormal glucose tolerance compared to SC mother, indicating the establishment of metabolic syndrome. Then, offspring subdivided according to maternal diet, O-SC pups birthed from mothers fed SC, whereas O-HF pups birthed from mothers fed HF diet, and morphological and functional experiments were performed in the small intestine 2 developmental ages, early suckling (P2) and late suckling (P15 ) to evaluate the contribute of maternal milk in the development of obesity. O-HF at P2 and P15 did not show significant changes in the morphology of the small intestinal wall (villus height, depth of the crypt, villus width near the crypt and thickness of the muscular layer) compared to O-SC. Moreover in agreement with morphological data, no difference has been found in the amplitude and frequency of the intestinal spontaneous mechanical activity from O-HF compared to O-SC. The contractile and relaxant responses to well know drugs as the muscarinic receptor agonist, carbachol, and the b-adrenergic receptor agonist, isoproterenol, were similar in both groups of animal. This study suggested that during lactation, maternal high fat feeding did not induce any compensatory and adaptative responses in gut that could suggest a predisposition to the development of pediatric obesity. Further experiments at later ages are currently in progress

Preventive effects of guanosine on intestinal inflammation in 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rats

Background: Guanosine, a guanine-based purine, is an extracellular signaling molecule exerting anti-inflammatory and antioxidative effects in several in vivo and in vitro injury models. We aimed to investigate its protective effects on 2, 4-dinitrobenzene sulfonic acid (DNBS)-induced colitis in rat. Methods: Rats were divided into five groups and colitis was induced by intracolonic instillation of DNBS (15 mg/rat). Guanosine (4 or 8 mg/kg) was administered for 6 days i.p. starting the day of the colitis induction. Body weight loss, stool consistency, colon weight/length, histological analysis, myeloperoxidase activity (MPO) and pro-inflammatory cytokine levels were assessed. Immunoblotting of nuclear factor-\u3baB (NF-\u3baB) p65 protein levels and detection of oxidative and nitrosative stress markers were also performed. Results: Guanosine, in a dose-dependent manner, significantly ameliorated the severity of DNBS-induced colitis, reducing body weight loss and diarrhea incidence, preventing the DNBS-induced macroscopic and microscopic damage to the colonic mucosa, and the MPO increase. Guanosine treatment also lowered interleukin-1\u3b2, interleukin-6, and tumor necrosis factor-\u3b1 mRNA levels. Importantly, guanosine in DNBS rats down-regulated the expression of NF-\u3baB p65 and the levels of reactive oxygen species and nitrite. Conclusions: In conclusion, guanosine exerts beneficial effects in DNBS-induced colitis in rats, through modulation of colonic inflammation, downregulating of NF\u3baB-mediated signaling