STUDIO DI VALUTAZIONE A LUNGO TERMINE DELLA FUNZIONE ESOCRINA E DEI VOLUMI PANCREATICI RESIDUI IN PAZIENTI SOTTOPOSTI A CHIRURGIA RESETTIVA

Introduzione L\u2019anastomosi del pancreas residuo con il tratto digestivo dopo duodenocefalopancreasectomia (DCP) rimane un aspetto critico nella gestione del paziente operato che pu\uf2 condizionare molteplici variabili che vanno dalla qualit\ue0 di vita allo sviluppo di insufficienza pancreatica esocrina. Spesso la tecnica standard di pancreo-digiuno-anastomosi (PJ) viene sostituita dalla pancreo-gastro-anastomosi (PG), di pi\uf9 facile esecuzione e gravata da minori complicanze. Ad oggi non esiste nessuno studio a lungo termine di comparazione tra i due tipi di anastomosi. Materiali e Metodi. Lo studio \ue8 stato condotto su 31 pazienti operati di DCP per neoformazione pancreatica, papillare o per pseudotumor infiammatorio, dal 2001 al 2006. Tutti sono stati ospedalizzati e sottoposti a studi morfologici e di funzione. I parametri studiati sono stati il volume pancreatico ed il diametro del dotto pancreatico principale (MRI), la funzione esocrina del pancreas (grassi fecale, elastasi fecale e vitamina D) e la funzione endocrina. La qualit\ue0 di vita e gli score sintomatologici sono stati valutati tramite il questionario EORTC QLQ-C30. E\u2019 stata riportata la media \ub1 1 errore standard. La normalit\ue0 della distribuzione \ue8 stata indagata mediante il test di Kolmogorov-Smirnov e la correlazione tra variabili indipendenti tramite test di Bravais-Pearson. Risultati. Sono stati studiati 31 pazienti, 15 con PG, 16 a PJ. Nessuna differenza \ue8 stata riscontrata in durata del follow-up, BMI, funzione endocrina, score sintomatologici e qualit\ue0 di vita. La funzione esocrina del pancreas risulta pi\uf9 alterata dopo PG che dopo PJ (steatorrea 26.6\ub14.1 vs 18.2\ub13.6 g/die; FE-1 170.2\ub125.5 vs 121.4\ub16.7 \u3bcg/g). Vi \ue8 una netta riduzione di vitamina D (maggiore nelle PG rispetto alle PJ) (18.1\ub11.8 vs 23.2\ub13.1 ng/ml).La MRI ho mostrato una severa riduzione del volume pancreatico residuo (pi\uf9 basso nelle PG rispetto alle PJ 26\ub13.1 vs 36\ub14.1 ml), e un netto aumento di diametro del dotto pancreatico residuo dopo PG (4.6\ub10.92 vs PJ 2.4\ub10.18 mm), indice di pancreatite ostruttiva. Conclusioni. Dopo interventi di DCP una marcata riduzione sia del volume pancreatico residuo sia della capacit\ue0 funzionale del pancreas rappresentano la regola, e portano quasi invariabilmente all\u2019insorgenza di steatorrea; la qualit\ue0 di vita, nel lungo termine, risulta pari a quella dei controlli; i sintomi digestivi suggestivi di malassorbimento o malnutrizione non differiscono da quanto osservato in una popolazione ambulatoriale \u201cnormale\u201d; si osserva invece frequentemente un deficit importante di micronutrienti, quale la vitamina D; risulta importante la necessit\ue0 di una terapia enzimatica sostitutiva in tutti i pazienti, indipendentemente dal corredo sintomatologico presentato.Introduction. The anastomosis of the residual pancreas with digestive tract after pancreaticoduodenectomy (PD) is a critical aspect in the management of the surgical patient that can affect many variables ranging from the quality of life to the development of exocrine pancreatic insufficiency. The standard technique of pancreo-jejunal-anastomosis (PJ) is often replaced by pancreo-gastro-anastomosis (PG), more easy to perform and with fewer complications. There is no long-term study of comparison between the two types of anastomosis. Material and Methods. We evaluated 31 patients after duodeno-cefalo-pancreatectomy (DCP) for pancreatic tumor from 2001 to 2006. All were hospitalized and submitted to morphological and functional studies. We studied the pancreatic volume and the diameter of the main pancreatic duct (MRI), the exocrine function of the pancreas (fecal fat, fecal-elastase and vitamin D) and endocrine function. The quality of life was assessed using the EORTC QLQ-C30. It was reported the mean \ub1 1 standard error. The normality of the distribution was investigated by the Kolmogorov-Smirnov test and the correlation between independent variables by the Bravais-Pearson test. Results. We studied 31 patients (15 with PG and 16 PJ). No difference was found in the duration of follow-up, BMI, endocrine function, symptom scores and quality of life. The exocrine pancreatic function is worse after PG than after PJ (steatorrhea 26.6 \ub1 4.1 vs 18.2 \ub1 3.6 g/day; FE-1 170.2 \ub1 25.5 vs 121.4 \ub1 6.7 \ub5g/g). There is a reduction of vitamin D (higher in PG compared to PJ) (18.1 \ub1 1.8 vs 23.2 \ub1 3.1 ng / ml). The MRI showed a severe reduction in the residual pancreatic volume (lower in PG than PJ: 26\ub13.1 vs 36\ub14.1 ml), and an increase in the diameter of the pancreatic duct after PG (4.6 \ub1 0.92 vs 2.4 \ub1 PJ of 0.18 mm), indicative of obstructive pancreatitis. Conclusion. After DCP there is a marked reduction both of the residual pancreatic volume both of the functional capacity of the pancreas which lead to steatorrhea. In the long term no differences in quality of life was found between operated patients and controls. Digestive symptoms suggestive of malabsorption or malnutrition not differ from that observed in a "normal" population-patient. However there is frequently a lack of important micronutrients, such as vitamin D and all patients needed important enzyme replacement, regardless of the set of symptoms presente

Rapid and comprehensive evaluation of (poly)phenolic compounds in pomegranate (punica granatum L.) juice by UHPLC-MSn

The comprehensive identification of phenolic compounds in food and beverages is a crucial starting point for assessing their biological, nutritional, and technological properties. Pomegranate (Punica granatum L.) has been described as a rich source of (poly)phenolic components, with a broad array of different structures (phenolic acids, flavonoids, and hydrolyzable tannins) and a quick, high throughput, and accurate screening of its complete profile is still lacking. In the present work, a method for UHPLC separation and linear ion trap mass spectrometric (MSn) characterization of pomegranate juice phenolic fraction was optimized by comparing several different analytical conditions. The best solutions for phenolic acids, anthocyanins, flavonoids, and ellagitannins have been delineated and more than 70 compounds have been identified and fully characterized in less than one hour total analysis time. Twenty-one compounds were tentatively detected for the first time in pomegranate juice. The proposed fingerprinting approach could be easily translated to other plant derived food extracts and beverages containing a wide array of phytochemical compounds

Sex-related differences in renal toxicodynamics in rodents

Introduction: An issue yet to be addressed, in the investigation of the xenobiotic toxicity, is a detailed characterization of the sex differences in toxicological responses. The \u2018sex issue\u2019 is significant in nephrotoxicology as the kidney is a relevant target organ for xenobiotics and few studies have approached this subject in the past. There is a strong need to improve our understanding regarding the influence of sex in toxicology, given their increased requirement to establish the limits of exposure to chemicals in the environment and at work. Areas covered: In this review, the authors provide the reader with the current knowledge of sex differences in kidney toxicity for rats and mice. To make the review easier to consult, these studies have been organized according to the class of xenobiotic. Expert opinion: From the analysis of the present knowledge emerges a dramatic need for information on sex differences in xenobiotics toxicity. Although animals are reasonably good predictors of adverse renal effects in patients, there is need to identify alternative methods (e.g. in vitro/ex vivo) to better study sex differences in organ toxicity

Hyaline droplet accumulation in kidney of rats treated with hexachloro-1:3-butadiene: influence of age, dose, and time-course

The present research investigates the occurrence of hyaline droplet (HD) accumulation related to age, dose, and time after treatment in male Wistar rats given a single i.p. injection of hexachloro-1:3-butadiene (HCBD). In the study on age, rats from 1 to 12 months of age were treated with 100 mg/kg b.w. HCBD dose. Rats treated at 2 months of age showed a greater accumulation of HD than the other age groups; HD accumulation was not observed in 1 month aged rats. In the dose-response study, the treatment with 25, 50, and 100 mg/kg b.w. at 2 months of age caused HD accumulation in the proximal convoluted tubule at all doses, with 100 mg/kg b.w. group slightly more affected.. Finally, in the time-course study, rats treated with a 100 mg/kg b.w. dose at 2 months of age and sacrificed at 6, 12, 24, 48, 72, and 96 hours post-dosing showed a time-related HD accumulation in term of incidence and severity, after 6 hours, with a peak at 24 and 48 hours and decreasing at 72 hours and 96 hours. The present results show that HD accumulation is an early finding and is unrelated to dose level and particularly evident in rats of 2 month of age. These findings in male rats treated with HCBD emphasized the importance of considering the age of rats at the start of a study the more sensitive model is used in the detection of nephrotoxic effects of chemicals

Fluorescence and Intraoperative Ultrasound as Surgical Adjuncts for Brain Metastases Resection: What Do We Know? A Systematic Review of the Literature

(1) Background: brain metastases (BMs) are the most common neoplasm of the central nervous system; despite the high incidence of this type of tumour, to date there is no universal consensus on the most effective treatment in patients with BMs, even if surgery still plays a primary role. Despite this, the adjunct systems that help to reach the GTR, which are well structured for other tumour forms such as ultrasound and fluorescence systems, are not yet well employed and standardised in surgical practice. The aim of this review is to provide a picture of the current state-of-art of the roles of iOUS and intraoperative fluorescence to better understand their potential roles as surgical tools. (2) Methods: to reach this goal, the PubMed database was searched using the following string as the keyword: (((Brain cerebral metastasis [MeSH Major Topic])OR (brain metastasis, [MeSH Major Topic])) AND ((5-ala, [MeSH Terms]) OR (Aminolevulinicacid [All fields]) OR (fluorescein, [MeSH Terms]) OR (contrast enhanced ultrasound [MeSH Terms])OR ((intraoperative ultrasound. [MeSH Terms]))) AND (english [Filter]) AND ((english [Filter]) AND (2010:2022 [pdat])) AND (english [Filter]). (3) Results: from our research, a total of 661 articles emerged; of these, 57 were selected. 21 of these included BMs generically as a secondary class for comparisons with gliomas, without going deeply into specific details. Therefore, for our purposes, 36 articles were considered. (4) Conclusions: with regard to BMs treatment and their surgical adjuncts, there is still much to be explored. This is mainly related to the heterogeneity of patients, the primary tumour histology and the extent of systemic disease; regardless, surgery plays a paramount role in obtaining a local disease control, and more standardised surgical protocols need to be made, with the aim of optimizing the use of the available surgical adjuncts and in order to increase the rate of GTR

Xylitol as a Hydrophilization Moiety for a Biocatalytically Synthesized Ibuprofen Prodrug

Biocatalyzed synthesis can be exploited to produce high-value products, such as prodrugs. The replacement of chemical approaches with biocatalytic processes is advantageous in terms of environmental prevention, embracing the principles of green chemistry. In this work, we propose the covalent attachment of xylitol to ibuprofen to produce an IBU-xylitol ester prodrug. Xylitol was chosen as a hydrophilizer for the final prodrug, enhancing the water solubility of ibuprofen. Ibuprofen is a nonsteroidal anti-inflammatory drug (NSAID) extensively used as an analgesic, anti-inflammatory, and antipyretic. Despite being the third-most-prescribed medicine in the world, the aqueous solubility of ibuprofen is just 21 mg/L. This poor water solubility greatly limits the bioavailability of ibuprofen. We aimed to functionalize ibuprofen with xylitol using the reusable immobilized N435 biocatalyst. Instead of a biphasic media, we proposed a monophasic reaction environment. The characterization of the IBU-xylitol ester was performed by 1H, 13C-NMR, DEPT, COSY, HMQC, HMBC, FTIR, and MS spectroscopy. Preliminary in vitro tests showed that this enzymatically synthesized prodrug of ibuprofen reduced the expression of the interleukin 8 genes in human bronchial epithelial cells (IB3-1) from cystic fibrosis (CF) patients

Gold(III)-dithiocarbamato anticancer agents: activity, toxicology and histopathological studies in rodents

Gold(III)-dithiocarbamato complexes have recently gained increasing attention as potential anticancer agents because of their strong tumor cell growth--inhibitory effects, generally achieved by exploiting non-cisplatin-like mechanisms of action. The rationale of our research work is to combine the antitumor properties of the gold(III) metal center with the potential chemoprotective function of coordinated dithiocarbamates in order to reduce toxic side effects (in particular nephrotoxicity) induced by clinically established platinum-based drugs. In this context, [Au(III) Br(2) (ESDT)] (AUL12) was proved to exert promising and outstanding antitumor activity in vitro and to overcome both acquired and intrinsic resistance showed by some types of tumors toward cisplatin. As a subsequent extension of our previous work, we here report on detailed in vivo studies in rodents, including antitumor activity toward three transplantable murine tumor models, toxicity, nephrotoxicity and histopathological investigations. Remarkably, the gold(III) complex AUL12 stands out for higher anticancer activity than cisplatin toward all the murine tumor models examined, inducing up to 80% inhibition of tumor growth. In addition, it shows low acute toxicity levels (lethal dose, LD(50) = 30 mg kg(-1) ) and reduced nephrotoxicity. Altogether, these results confirm the reliability of our drug design strategy and support the validation of this gold(III)-dithiocarbamato derivative as a suitable candidate for clinical trials

Evaluation of aging influence on renal toxicity caused by segment-specific nephrotoxicants of the proximal tubule in rat

Little is known concerning the sensitivity of aged rats to xenobiotics inducing kidney damage. To increase this knowledge, the age-dependent response of the kidney to hexachloro-1:3-butadiene (HCBD) or potassium dichromate (chromate) has been investigated. Rats have been treated at different ages with a single dose of segment-specific nephrotoxicants of the proximal tubule, chosen on the basis of their specificity for S3 and for S1-S2 segments, respectively. The toxicological impact of these xenobiotics has been evaluated through biochemical and genomic markers, and histopathological investigation of kidney samples. HCBD treatment induced tubular necrosis of the S3 segment of the proximal tubule associated with changes of toxicological markers unrelated to the age. On the contrary, chromate treatment induced an increased kidney damage related to the rat age. In fact, histopathological investigation revealed that at 1 month of age tubular vacuolar degeneration was seen affecting S1-S2 segments of the proximal tubule, whereas at 3 months of age tubular necrosis occurred in the same segments associated with tubular dilation of the distal portions. Consistently, biochemical analysis confirms a direct correlation among genomic and biochemical marker variability and animal age. Altogether, the results show that during aging there is an increased sensitivity of kidney to chromate but not to HCBD-induced damage and evidence differential age-related selectivity of rats for nephrotoxic compounds. Significance for human risk assessment is discussed