Mortalità e Complicanze clinico-nutrizionali a lungo termine nell’Anoressia Nervosa di Tipo Restrittivo (malnutrizione secondaria a disturbi cronici restrittivi del comportamento alimentare)

Nei tre anni del corso di dottorato di ricerca in Terapie Avanzate Medico Chirurgiche presso il Dipartimento di Medicina Clinica e Chirurgia dell’Università degli Studi di Napoli “Federico II”, ho portato avanti un progetto di ricerca volto a valutare lo stato nutrizionale e le complicanze cliniche a lungo termine in pazienti con DCA. In particolare mi sono soffermata su tre tematiche: 1) Mortalità in pazienti affette da AN con un follow up interrotto da almeno 10 anni La valutazione della mortalità nei DCA, da estendere al più alto numero di giovani pazienti di cultura e nazionalità differenti, rimane un obiettivo primario per il monitoraggio della gravità di tale malattia; lo studio di eventuali fattori predittivi potrebbe essere utile per migliorare i protocolli di diagnosi e terapia. L’obiettivo di tale studio è stato di valutare la mortalità a lungo termine in una popolazione di pazienti anoressiche, confrontando i dati con quelli disponibili da altri studi recenti sui tassi di mortalità, e aumentando la durata dell’osservazione rispetto agli ultimi follow up svolti presso questo Dipartimento. (De Filippo et al 2000; Signorini et al. 2006). 2) Lo stato di nutrizione biochimico, funzionale e clinico generale di un campione di pazienti anoressiche a distanza di 10 anni dalla ultima osservazione clinica ambulatoriale. Si è voluto studiare, in un gruppo di pazienti richiamate, le condizioni cliniche generali a distanza di più dieci anni dalla diagnosi certa di anoressia nervosa sia dal punto di vista biochimico, funzionale che clinico-nutrizionale: tra l’altro come si modificano eventualmente i parametri di valutazione della composizione corporea e ossea, e la funzione cardiaca. Inoltre i dati ottenuti in queste pazienti alla prima osservazione sono stati confrontati con il campione iniziale generale, per verificare se il gruppo delle pazienti richiamate fosse rappresentativo dello stesso campione generale. 3)Valutazione delle condizioni generali di un gruppo di pazienti ricontattate dopo 10 anni dall’ultima osservazione Fra i fattori predisponenti svolgono un ruolo importante quelli socioeconomici e culturali. Con apposito questionario ( somministrabile anche per via telefonica) si è voluto verificare le condizioni cliniche generali secondo quanto riferito dalle pazienti, ed ottenere una descrittiva delle variabili socio-demografiche delle stesse dopo vari anni, verificando la concordanza con quanto segnalato in letteratura riguardo le caratteristiche culturali e sociali tipiche delle pazienti anoressiche

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)

Fecal Short Chain Fatty Acids and Dietary Intake in Italian Women With Restrictive Anorexia Nervosa: A Pilot Study

Nutritional disorders such as Anorexia Nervosa (AN) can shape the composition of gut microbiota and its metabolites such as short chain fatty acid (SCFA). This study aims to compare fecal SCFA along with dietary intake of women with restrictive AN (r-AN = 10) and those of sex-matched lean controls (C = 8). The main fecal short chain fatty acids (SCFA) were assessed by gas chromatography equipped with a flame ionization detector. All participants completed 7-day food record and underwent indirect calorimetry for measuring resting energy expenditure (REE). Butyrate and propionate fecal concentrations were significantly reduced in r-AN patients compared to controls. The intake of carbohydrate and fat was significantly lower in r-AN patients than controls as well as energy intake and REE; whereas the amount of protein and fiber did not differ between groups. These preliminary results showed that r-AN patients had a reduced excretion of fecal SCFA, likely as a mechanism to compensate for the lower energy and carbohydrate intake observed between groups. Therefore, further studies need to be performed in patients with AN to explore the link between nutritional disorders, gut microbiota and its metabolites

Body composition, segmental bioimpedance phase angle and muscular strength in professional volleyball players compared to a control group

Background: The assessment of body composition is central in evaluating athletes' nutritional status and the effects of training. The aim of this study was to evaluate body composition and the relation between bioimpedance phase angle (PhA) and muscular strength in elite female volleyball players. Methods: Twelve volleyball players (age 23.8±3.6 years; weight 63.0±5.1 kg; height 170±4 cm; BMI 21.9±1.3 kg/m2) and 22 non-athletic females, who served as a control group (age 23.6±2.0 years; weight 60.7±4.8 kg; height 167±5 cm; BMI 21.9±1.3 kg/m2), participating in the study. Skinfold thickness measures were used and segmental bioelectrical impedance analysis (BIA) was performed. Additionally, hand grip strength was used to evaluate muscular strength. Results: Volleyball players had lower FM and higher FFM than controls (FM(kg)=15.7±2.7 vs. 18.0±3.0, P=0.036; FM(%)=24.8±3.0 vs. 29.5±3.8, P=0.001; FFM(kg)=47.4±3.5 vs. 42.8±3.6, P=0.001). Both whole-body and segmental PhA were higher in volleyball players (P<0.05) than in controls, whereas no differences were observed for hand grip strength. A positive relation was found between hand grip strength and whole-body and upper limbs PhA in all subjects, resulting stronger in volleyball players (r=0.696, P=0.012 and r=0.821, P=0.001, respectively). Conclusions: The data confirmed that body composition differed between volleyball players and non-athletic subjects. In addition, a strong correlation between PhA and hand grip strength in both volleyball players and in controls was found. However, further evaluations are needed to investigate the use of hand grip strength in sport performance

Resting Energy Expenditure, Body Composition and Phase Angle in Anorectic, Ballet Dancers and Constitutionally Lean Males

Background: The prevalence of anorexia nervosa among males is increasing but few data are available in the literature. This cross sectional study aims to evaluate resting energy expenditure (REE) and phase angle as a marker of qualitative changes of fat free mass (FFM) in three leanness groups as compared with control subjects. Methods: 17 anorectic (AN) males, 15 constitutionally lean (CL) individuals, 12 ballet dancers (DC), and 18 control (CTR) subjects were evaluated. REE was measured by indirect calorimetry (V max29- Sensormedics), and body composition was evaluated by bioimpedance analysis (BIA) at 50 kHz (DS Medica). Phase angle (a bioimpedance variable related to nutritional status) was used to evaluate differences in FFM characteristics between these three types of leanness. Results: REE, adjusted for FFM and fat mass (FM), were significantly higher in CL and lower in AN individuals (1783 ± 47 vs. 1291 ± 58 kcal, p < 0.05) compared to the other groups. Body composition was similar in AN and CL whereas dancers had the highest FFM (58.9 ± 4.8 kg, p < 0.05); anorectic males showed the lowest phase angle (5.8 ± 1.2 degrees vs. other groups, p < 0.05) and dancers the highest phase angle (7.9 ± 0.7 degree vs. other group, p < 0.05). Conclusions: Our findings confirm that phase angle could be a useful marker of qualitative changes, above all in the field of sport activities. On the other hand, there is the need to further evaluate the relationship between resting energy expenditure, body composition and endocrine status in different conditions of physical activity and dietary intake

Evaluation of the Nutritional Status of Gaucher Disease Type I Patients under Enzyme Replacement Treatment

(1) Background: Gaucher disease (GD) is a rare lysosomal storage disease. The few studies analyzing Resting Energy Expenditure (REE) in GD involved mainly untreated patients and supported a hypermetabolic condition possibly due to the associated inflammatory state. Definitive conclusions could not be drawn also because of the heterogeneity and the small size of the samples investigated. In order to expand current knowledge concerning, in particular the condition of patients under Enzyme Replacement Therapy (ERT), we evaluated the nutritional status of a relatively large sample of GD patients followed at Federico II University Hospital in Naples, Italy. (2) Methods: The study, having a cross-sectional design and involving 26 patients on ERT, included routine biochemical analyses, bioelectrical impedance analysis, indirect calorimetry, and administration of food frequency and physical activity questionnaires. The results in GD patients were compared with those from an appropriate control group. (3) Results: GD patients had normal biochemical parameters in 80% of cases, except for HDL-cholesterol, consumed a hyper-lipidic diet, and had a 60% prevalence of overweight/obesity. Body composition did not differ between patients and controls; however, measured REE was significantly lower than predicted and was reduced in comparison with the healthy controls. (4) Conclusions: This study provided novel elements to the present knowledge about REE and the nutritional status of GD patients under ERT. Its results warrant confirmation in even larger GD population samples and a more in-depth investigation of the long-term effects of treatment superimposed on the basic pathophysiological disease condition

Long-Term Outcomes from a 10-Year Follow-Up of Women Living with a Restrictive Eating Disorder: A Brief Report

Background: This study aimed to evaluate several socio-demographic and long-term clinical outcomes in a cohort of women living with a restrictive eating disorder. Methods: Patients were asked to fill in a general data collection form aiming to investigate their current conditions and to attend the outpatient unit for a 10-year follow-up clinical and laboratory evaluation. Results: Forty-four patients completed the follow-up general data collection form and 20 agreed to attend the outpatient unit for the 10 year-follow-up evaluation. In total, 52% of patients were single, 55% had achieved a university degree, and 55% had steady employment. After 10 years, there was a clear improvement in biochemical markers, but cholesterol levels were still slightly high. The prevalence of osteopenia in the whole sample was 70% when measured on the lumbar column and 20% on the total body, while osteoporosis was found in 10% of patients and only on the lumbar column. Conclusion: According to the collected data, women with a history of restrictive eating disorders appear to re-adapt well to social life by obtaining the level of their unaffected peers in terms of education and employment

Structural modifications of the serotonin 5-HT7 receptor agonist N -(4-cyanophenylmethyl)-4-(2-biphenyl)-1-piperazinehexanamide (LP-211) to improve in vitro microsomal stability: A case study

The 5-HT7 serotonin receptor is revealing a promising target for innovative therapeutic strategies of neurodevelopmental and neuropsychiatric disorders. Here, we report the synthesis of thirty long-chain arylpiperazine analogs of the selective and brain penetrant 5-HT7 receptor agonist LP-211 (1) designed to enhance stability towards microsomal oxidative metabolism. Commonly used medicinal chemistry strategies were used (i.e., reduction of overall lipophilicity, introduction of electron-withdrawing groups, blocking of potential vulnerable sites of metabolism), and in vitro microsomal stability was tested. The data showed that the adopted design strategy does not directly translate into improvements in stability. Instead, the metabolic stability of the compounds was related to the presence of specific substituents in well-defined regions of the molecule. The collected data allowed for the construction of a machine learning model that, in a given chemical space, is able to describe and quantitatively predict the metabolic stability of the compounds. The majority of the synthesized compounds maintained high affinity for 5-HT7 receptors and showed selectivity towards 5-HT6 and dopamine D2 receptors and different selectivity for 5-HT1A and α1 adrenergic receptors. Compound 50 showed 3-fold higher in vitro stability towards oxidative metabolism than 1 and was able to stimulate neurite outgrowth in neuronal primary cultures through the 5-HT7 receptor in a shorter time and at a lower concentration than the agonist 1. A preliminary disposition study in mice revealed that compound 50 was metabolically stable and was able to pass the blood-brain barrier, thus representing a new tool for studying the pharmacotherapeutic potential of 5-HT7 receptor in vivo

The 5-HT7 Receptor Triggers Cerebellar Long-Term Synaptic Depression via PKC-MAPK

The 5-HT7 receptor (5-HT7R) mediates important physiological effects of serotonin, such as memory and emotion, and is emerging as a therapeutic target for the treatment of cognitive disorders and depression. Although previous studies have revealed an expression of 5-HT7R in cerebellum, particularly at Purkinje cells, its functional role and signaling mechanisms have never been described. Using patch-clamp recordings in cerebellar slices of adult mice, we investigated the effects of a selective 5-HT7R agonist, LP-211, on the main plastic site of the cerebellar cortex, the parallel fiber-Purkinje cell synapse. Here we show that 5-HT7R activation induces long-term depression of parallel fiber-Purkinje cell synapse via a postsynaptic mechanism that involves the PKC-MAPK signaling pathway. Moreover, a 5-HT7R antagonist abolished the expression of PF-LTD, produced by pairing parallel fiber stimulation with Purkinje cell depolarization; whereas, application of a 5-HT7R agonist impaired LTP induced by 1 Hz parallel fiber stimulation. Our results indicate for the first time that 5-HT7R exerts a fine regulation of cerebellar bidirectional synaptic plasticity that might be involved in cognitive processes and neuropsychiatric disorders involving the cerebellum