Trazodone, insonnia e sistema melatoninergico: valutazione della via metabolica nel siero e nelle urine di pazienti depressi in terapia.

Lo scopo di questa tesi è stato quello di valutare eventuali influenze dell’antidepressivo atipico Trazodone (Trittico®) su alcuni meccanismi che sottendono al controllo del metabolismo melatoninergico in pazienti depressi con disturbi del sonno, al fine di poterne in futuro ottimizzarne la terapia farmacologica. Il Trazodone appartenente alla classe degli Antagonisti-2-Serotoninergici/Inibitori della ricaptazione (SARI). Tale farmaco è stato approvato dalla FDA (Food and Drug Administration ente governativo statunitense che si occupa della regolamentazione dei prodotti alimentari e farmaceutici) per il trattamento delle forme depressive maggiori, ma viene anche utilizzato “off-label”, a dosaggi ridotti, nell’insonnia. Il suo meccanismo d’azione, in particolare quello che ne determina il successo nel trattamento dei disturbi del sonno, è ancora poco chiaro. Un recente studio (Morera et al. 2009) ha riportato un aumento dei livelli plasmatici di melatonina durante la notte, in seguito al trattamento con Trazodone, in analogia con altri farmaci antidepressivi quali la fluvoxamina; non sono tuttavia ancora noti i bersagli molecolari del farmaco, che sarebbero in grado di incrementare le concentrazioni dell’ormone pineale in circolo. Il lavoro di questa tesi rientra in uno studio pilota di carattere biochimico-clinico, approvato dal comitato di bioetica dell’ Università di Pisa. I pazienti introdotti nel presente studio sono stati valutati clinicamente tramite gli strumenti per la diagnosi di disturbo psichiatrico (criteri DSM-IV; questionario SCID) e questionario di qualità del sonno ed i parametri biochimici sono stati analizzati in campioni di siero ed urine prima e dopo trattamento con dosaggi tra 15-20mg di Trazodone. Sulla base dei dati raccolti è stato quindi testato un tipo di monitoraggio terapeutico atto a valutare la risposta individuale al farmaco, al fine quindi di ottimizzare e personalizzare la terapia. In particolare, sono stati valutati i livelli di melatonina in campioni di siero, sia tramite metodica HPLC-PED (rilevazione elettrochimica) e test immuno-enzimatico ELISA ed i livelli di 6-idrossimelatonina solfato (principale metabolita della melatonina) in campioni di urine della notte mediante kit ELISA; sui campioni di siero dei pazienti post-trattamento (circa 1 mese) sono inoltre stati valutati i livelli di Trazodone e m-CPP con metodica HPLC-UV-PDA (rilevazione UV a fotodiodi-lettura spettrale). Oltre a ciò sono state valutate, per le due tecniche analitiche utilizzate (HPLC ed ELISA) il loro grado di riproducibilità e/o complementarietà. I dati ottenuti hanno mostrato una notevole variabilità interindividuale riguardante tutti i parametri analizzati, non facendo emergere correlazioni statisticamente significative, ma solamente dei trend: il trattamento con TRZ sembra andare a migliorare sia il grado di depressione che d’insonnia ed i parametri biologici testati confermano l’andamento; la concentrazione plasmatica di melatonina, valutata nella prima mattina, sembra diminuire in buona parte dei pazienti, mentre la 6-idrossi-melatonina solfato nelle urine della notte, va ad aumentare. Per quanto riguarda la comparazione tra la metodica HPLC-PED ed ELISA per la determinazione della melatonina nel siero pre e post-trattamento con il farmaco, sono state ottenute buone correlazioni sia al T0 (pre-trattamento)r= 0,9374, p=0.0006 che al T1 (post-trattamento)r= 0,9199, p=0.0012; confermando che entrambe le metodiche sono valide e confrontabili. Concludendo, i dati attualmente in nostro possesso non ci permettono ancora di trarre conclusioni, né di smentire l’ipotesi che il Trazodone influenzi in qualche modo la via melatoninergica, ma rappresentano un punto di partenza verso la comprensione del meccanismo d’azione del farmaco sulla biochimica del sonno. Per un miglioramento dello studio si rende necessario pertanto il reclutamento di un numero più consistente di pazienti

Estimated requirements of net energy, digestible protein and NDF intake of young Chianina bulls from 400 kg liveweight to slaughter

Three equations have been elaborated and proposed to predict the requirements of net energy and protein digestible in the intestine and NDF voluntary intake of growing young Chianina bulls, starting from 400 kg live weight. The animals examined in the present study were 100 young Chianina bulls starting from about 400 kg live weight, at 10 months of age, up to the average slaughter weight of 800 kg at 20 months average age. The diet was based on hay and concentrates. The equation for the prediction of net energy fits quite perfectly to another experimental equation formerly proposed by Giorgetti and is characterised by a very high value of the correlation coefficient for the regression comparison between observed and predicted figures (R2=0.90). The statistical reliance degree of the PDIN prediction equation is lower, but still very good (R2=0.75 between observed and predicted values), but that of the estimate of NDF daily intake resulted very poor (R2=0.26 between observed and predicted values), probably due to the non homogeneity of the intake capacity of the 100 examined animals. The correlation between daily gains and the concentration of NDF in the diet DM results good (R2=0.87), showing that young Chianina bulls take advantage of the diet fibre. Further useful indications on the nutritional and dietary requirements of young Chianina bulls are added to the scarce information currently available

Effect of tannin supplementation on nitrogen digestibility and retention in growing pigs.

Two levels (0.25% and 0.5%) of water soluble chestnut tannin were added to the diet of growing pigs in a 40 days feeding trial, from the average body weight of 76kg up to about 110kg. As expected, a significant depression of the apparent digestibility of both dietary dry matter and nitrogen was recorded with level 0.5%, but the decrease of retained nitrogen was not statistically significant, due to the higher dietary nitrogen. It is concluded that the present preliminary study showed that a concentration of 250g tannin per 100kg mixed feed does not appreciably influence the animals' performance. The aspect of a possible beneficial effect on the gut microflora deserves further studies

Effect of forage /concentrate ratio and soybean oil supplementation on in vitro fatty acid profile of sheep rumen liquor.

In an in vitro trial, the effect of forage/concentrate ratio (F/C) and soybean oil (SO) supplementation on rumen liquor fatty acids profile was studied with the aim to evaluate changes in the profiles of biohydrogenation intermediates during the fermentation process. Feed samples of four diets were inoculated with sheep rumen liquor: i) high F/C and no SO; ii) high F/C and SO; iii) low F/C and no SO; iv) low F/C and SO. Fermentation times were 6, 12 h. Trans fatty acid were formed when oil supplement or a low forage content were present in the diets, but at different times of fermentation, as a consequence of a shift from the usual rumen biohydrogenation pathway. In fact, when a higher forage percentage was included in the diet, the alternative pathways of rumen biohydrogenation did not occur; trans10 C18:1 concentration was low and neither trans10, cis12 CLA nor trans, trans CLA appeared

Use of a citrus by-product in broilers diets

The European Union is about to ban antibiotics as growth promoters in animal feeds. Organic products have been recently revalued and the animal science research showed a great interest in the study of alternative natural nutraceutical products in animal feeding. Flavonoids are plant pigments able to inhibit or kill many bacterial strains, to destroy some pathogenic protozoa and to scavenge free radicals

effect of butyric acid on the performance and carcass yield of broiler chickens

Short-chain fatty acids such as butyrate are considered potential alternatives to antibiotic growth promoters. The efficacy of butyric acid on performance and carcass characteristics of broiler chickens was tested in two studies. The effect of dietary butyrate on the ability to withstand coccidial oocyte challenge also was investigated. In experiment 1, male broiler chickens were fed diets supplemented with 0 or 11 ppm virginiamycin or 0.2 or 0.4% butyric acid (as mono-, di-, and triglyceride). In experiment 2, broilers were fed bacitracin methylene disalicylate or 0.1 or 0.2% butyric acid. In another trial, birds vaccinated against coccidiosis were challenged with oocytes at 21 d and examined 6 d later. In experiment 1, diet treatments had no effect on body weight gain. Feed intake of the birds fed 0.4% butyric acid was decreased (P < 0.01) compared with birds fed the nonmedicated diet during the starter period, whereas birds fed 0.2% butyric acid had similar feed intake to the control birds. In experiment 2, diet treatments did not affect the performance of broiler chicks while carcass weight and breast meat yield increased (P < 0.01) in birds fed 0.2% butyric acid. With oocyte challenge, birds that had received butyric acid before challenge showed higher growth rate following the challenge compared with birds that received nonmedicated feed. Bacitracin decreased (P < 0.05%) duodenal villi crypt depth, whereas villus length was similar in birds fed butyric acid or the nonmedicated control diet. These results show that 0.2% butyric acid can help to maintain the performance and carcass quality of broilers, especially in vaccinated birds challenged with coccidiosis

Effect of three species of herbage (Medicago sativa, Lolium multiflorum, Avena sativa) on in vitro ruminal production of conjugated linoleic and vaccenic acids

Little information is available about the effect of different forage species on the rumen biohydrogenation process. The aim of the present work is to compare the in vitro production of CLA and C18:1 isomers after incubation of three different herbage species in rumen liquor from sheep. Pasture herbage samples of lucerne (Medicago sativa; MS), ryegrass (Lolium multiflorum; LM) and oats (Avena sativa; AS) were submitted to in vitro fermentation with sheep rumen inoculum. Samples were collected at 2, 4, 6 and 8 hours of fermentation. The fatty acid profile of MS was characterised by 11.62 (g/100 g of lipid extract) of linoleic acid (LA) and 27.08 (g/100 g of lipid extract) of α-linolenic acid (LNA), whereas LA in the other two herbages was 6.60 (g/100 g of lipid extract) and 6.95 (g/100 g of lipid extract) in AS and LM, respectively; LNA was 52.20 (g/100 g of lipid extract) and 54.49 (g/100 g of lipid extract) in AS and LM, respectively. The crude fat content of botanical species was respectively 11.90 (g/100g DM) for AS, and 15.77 (g/100g DM) for LM and 26.17 (g/100g DM) for MS. Rumenic acid (RA, cis-9, trans-11 CLA) was the predominant CLA isomer and the maximum yield was attained with AS after 6 hours of fermentation (0.81 g/100 g of lipid extract); RA concentration remained quite low with the other two herbages. The concentration of the other isomer (trans-10, cis-12 CLA) was always very low; the maximum yield (0.09 g/100 g of lipid extract) was reached after 6 hours with AS. The maximum yield of vaccenic acid (VA, trans-11 C18:1) was reached after 8 hours with MS (2.64 g/100 g of lipid extract). This herbage also produced the highest amount of trans-10 C18:1 at 6 and 8 hours (0.17 g/100 g of lipid extract). AS appeared to have induced the highest amounts of RA relative to the other two forages. The differences in conjugated dienes and C18:1 isomers content during fermentation could be due not only to different amounts of LA or LNA in the herbage, but also to different releasing times of FA from the plant substrate

Mixtures of mono-, di- and tri-glycerides as energy supplements to broilers' diets

Mixtures of mono-, di- and tri-glycerides from olive oil (MDT) were added to: palm oil (PO), olive oil (OO), soybean oil (SO), free fatty acids from palm oil (PFA), free fatty acids from olive oil (OFA). The compound mixtures were used as energy supplements in the diets of broiler chickens in comparison with plain SO and plain animal fat (AF). Two hundred and ten birds were randomly allotted to 7 dietary treatments with the diverse oil sources: 6 birds per cage, 5 cages per treatment. The effects of the treatments on growth rates, feed/gain ratios and acidic composition of abdominal fat of hybrid Ross 308 female chickens were studied. The animals were slaughtered at the end of the trial, at day 35. The breast meat quality was then evaluated by a panel of 15 trained members and analysed for shelf life duration. The AF treat- ment gave the highest weight gain, but only in the first week. MDT + OO (50/50) resulted the best combination, with slight, non significant, better performances and a decidedly better quality in terms of acidic composition of abdominal fat, taste and juiciness of breast meat and shelf life

Monobutirryne: a novel feed additive in the diet of broiler chickens.

Purpose of the present work was to validate the monoglyceride of butyric acid (MB) as an alternative to antibiotics as growth promoters in the diet of broiler chickens. The approach is a kind of prolongation of previous works, in which a blend of mono-, di- and tri-glycerides of butyric acid have been previously tested. The results indicated that MB was very efficient in limiting the mortality of birds challenged with Eimeria spp., but did not appreciably impair the performance of unchallenged birds. In conclusion, the metabolisable energy content of MB appeared comparable with that of soybean oil and MB a reliable coccidiostat