Study of tocopherol content and its potential antioxidant activity in commercial lipid emulsions for parenteral nutrition.

The objective of this study was to determine the content and evaluate the potential antioxidant effect of tocopherols in commercially available lipid emulsions, using a simple validated method adequate for further routine use. During the study, variability between manufacturers as well as between three non-consecutive batches of the same emulsion was observed. Furthermore, addition of α-tocopherol to lipid emulsions as excipient yields more stable emulsions and potentially a beneficial clinical effect. It was concluded that the variation of the tocopherol content between batches implies the importance of control and specification of tocopherol content by the manufacturers.

Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

[Standard parenteral nutrition preparations and caloric adjustment]. / Preparados estándar de nutrición parenteral y ajuste calórico.

INTRODUCTION: In parenteral nutrition it is necessary to adjust the intake to the estimated caloric requirements. These needs may be achieved by the use of bi- or tricameral nutrition (EPN), although they present some rigidity regarding their composition. OBJECTIVE: To assess the adequacy of caloric intake using EPN, to determine the factors conditioning it and the associated complications. METHODS: Cohort, prospective, and observational study for 9 months in surgical patients. The calculated needs were compared with actual intake. The factors conditioning the excess and deficit (weight, age, stress factor, height, glycemia, and triglyceridemia) were studied by means of a multivariant method. The metabolic complications associated to the excess or deficit (hyperglycemias, hypertriglyceridemias) were studied by using the Student's t test. The theoretical calculations with the Harris-Benedict and the Mifflin equations were compared by lineal correlation regression. RESULTS: 94 patients were studied. In 87% of them, the caloric intake was within the +/- 15% range of the theoretical mean. Thirty patients had caloric excess, whereas 61 had deficit. Patients with high weight (> 68 kg), stress factor > 1.2, and hypertriglyceridemias (> 3 mmol/L) had higher risk for caloric deficit. Twenty two point eight percent had hyperglycemias that were correlated with caloric excess. Nineteen point eight percent had hypertriglyceridemias associated to caloric deficit. When comparing both formulas, the values correlated well except for those patients with low weight and advanced age. DISCUSSION: Although EPN fits the caloric requirements in most of the patients, in those with high weight, hypercatabolism, and hypertriglyceridemia there is a risk for caloric deficit.

Efficacy of enteral decontamination in the prevention of anastomotic dehiscence and pulmonary infection in esophagogastric surgery.

Our aim in this study is to evaluate the efficacy of decontamination of the high digestive tract in reducing the incidence of anastomotic dehiscence, pulmonary infection and mortality after resective gastro-esophageal surgery. A prospective randomized and double-blinded study was conducted in patients undergoing total gastrectomy for gastric cancer and esophagectomy for esophageal cancer. Two groups were studied: group A patients were given erythromycin + gentamicine + nistatine sulfate orally; group B patients were given placebo. Mortality, incidence of anastomotic dehiscence and incidence of pulmonary infection were the end points evaluated. One hundred and nine consecutive patients were randomized. Eighteen (16.5%) were excluded. From the 91 patients who were evaluated, 42 (46.2%) received an esophagectomy and 49 (53.8%) had a total gastrectomy. Esophagectomies showed: a 0% rate of anastomotic dehiscence in group A and 12.5% in group B, P = 0.176; a pulmonary infection rate of 22.2% in group A and 29.1% in group B, P = 0.443; and mortality rate was 0% in group A and 12.5% in group B, P = 0.176. After gastrectomy, anastomotic dehiscence rate was 4.5% in group A and 0% in group B, P = 0.449; pulmonary infection rate was 4.5% in group A and 11.1% in group B, P = 0.387 and mortality was 9% in group A and 0% in group B, P = 0.196. Decontamination protocol does not help in decreasing the incidence of anastomotic dehiscence, pulmonary infection and mortality in the present study. Nevertheless, there seems to be a tendency to low pulmonary infection after gastrectomy and esophagectomy and to improve the incidence of anastomotic dehiscence after esophagectomy. Further studies are needed to re-evaluate these findings.

Synthesis and functionalization of dextran-based single-chain nanoparticles in aqueous media.

Water-dispersible dextran-based single-chain polymer nanoparticles (SCPNs) were prepared in aqueous media and under mild conditions. Radiolabeling of the resulting biocompatible materials allowed the study of lung deposition of aqueous aerosols after intratracheal nebulization by means of single-photon emission computed tomography (SPECT), demonstrating their potential use as imaging contrast agents.

[Multicenter study on the prevalence of hyperglycemia among hospitalized patients with parenteral nutrition]. / Estudio multicéntrico de prevalencia de hiperglucemia en pacientes hospitalizados con nutrición parenteral.

OBJECTIVE: The aim of this cross-sectional national multicentric study was to determine the prevalence of hyperglycemia in patients with parenteral nutrition and to assess other clinical factors associated with this complication. METHOD: All Spanish hospital pharmacy services were invited to participate in the study. RESULTS: Twenty eight (28) pharmacy services agreed to participate. The study included 442 patients. The prevalence of hyperglycemia (plasma levels > 200 mg/dL) was 26.7%. Eighty four point two per cent of the patients received less than 3.5 mg/kg/minute of glucose, this infusion rate being considered as the safe threshold. In most patients, follow-up of glycemia was based on capillary blood determination with reactive strips and in 27.6% of the cases in which insulin was prescribed, it was added to the parenteral nutrition bag, in full or in part. No significant correlations were found between glycemia and the clinical factors studied (disorders, fever, medication), except for insulin. CONCLUSIONS: This national multicentric study of the prevalence of hyperglycemia among patients with parenteral nutrition, leaded by hospital pharmacists, was a joint effort aimed to better understand this metabolic complication. Findings are consistent with those reported by other authors and have allowed us to describe the current situation.

Ion beam induced 18F-radiofluorination: straightforward synthesis of gaseous radiotracers for the assessment of regional lung ventilation using positron emission tomography.

A simple, straightforward and efficient method for the synthesis of [18F]CF4 and [18F]SF6 based on an ion beam-induced isotopic exchange reaction is presented. Positron emission tomography ventilation studies in rodents using [18F]CF4 showed a uniform distribution of the radiofluorinated gas within the lungs and rapid elimination after discontinuation of the administration.

Use of colistin in the treatment of multiple-drug-resistant gram-negative infections.

PURPOSE: The use of colistin for the treatment of infections caused by multiple-drug-resistant (MDR) gram-negative microorganisms was studied. METHODS: The efficacy of colistin for treating infections caused by MDR gram-negative microorganisms and the development of renal toxicity were studied in hospitalized adult patients in Spain. Patients treated between January 2001 and October 2001 were included. RESULTS: Over the study period, 71 courses of inhaled colistin, 12 courses of i.v. or intramuscular (i.m.) colistin, and 2 courses of intrathecal colistin were administered to 80 patients. All were infected by MDR organisms: 69 (86%) by Acinetobacter baumannii and 11 (14%) by Pseudomonas aeruginosa. In 41 patients (51%), the episodes were caused by A. baumannii strains susceptible exclusively to colistin. The causative organisms were cleared in 92% of the patients from whom posttreatment repeat specimens were obtained. The in-hospital mortality rate was 18% (14 patients). There were no significant changes in mean serum urea or creatinine concentrations in patients receiving i.v. or i.m. therapy. CONCLUSION: Colistin was used in 80 patients infected with A. baumannii or P. aeruginosa and appeared to be efficacious and safe.

Straightforward synthesis of radioiodinated Cc-substituted o-carboranes: towards a versatile platform to enable the in vivo assessment of BNCT drug candidates.

Due to their high boron content and rich chemistry, dicarba-closo-dodecaboranes (carboranes) are promising building blocks for the development of drug candidates with application in Boron Neutron Capture Therapy. However, the non-invasive determination of their pharmacokinetic properties to predict therapeutic efficacy is still a challenge. Herein, we have reported the unprecedented preparation of mono-[(125)I] iodinated decaborane via a catalyst-assisted isotopic exchange. Subsequent reactions of the radiolabelled species with acetylenes in acetonitrile under microwave heating yield the corresponding (125)I-labelled, Cc-substituted o-carboranes with good overall radiochemical yields in short reaction times. The same synthetic strategy was successfully applied to the preparation of (131)I-labelled analogues, and further extension to other radioisotopes of iodine such as (124)I (positron emitter) or (123)I (gamma emitter) can be envisaged. Hence, the general strategy reported here is suitable for the preparation of a wide range of radiolabelled Cc-substituted o-carborane derivatives. The labelled compounds might be subsequently investigated in vivo by using nuclear imaging techniques such as Single Photon Emission Computerized Tomography or Positron Emission Tomography.

Visualisation of dual radiolabelled poly(lactide-co-glycolide) nanoparticle degradation in vivo using energy-discriminant SPECT.

The determination of nanoparticle (NP) stability and degradation in vivo is essential for the accurate evaluation of NP biodistribution in medical applications and for understanding their toxicological effects. Such determination is particularly challenging because NPs are extremely difficult to detect and quantify once distributed in a biological system. Radiolabelling with positron or gamma emitters and subsequent imaging studies using positron emission tomography (PET) or single-photon emission computerised tomography (SPECT) are some of the few valid alternatives. However, NPs that degrade or radionuclides that detach or are released from the NPs can cause artefact. Here, submicron-sized poly(lactide-co-glycolide) nanoparticles (PLGA-NPs) stabilised with bovine serum albumin (BSA) were dual radiolabelled using gamma emitters with different energy spectra incorporated into the core and coating. To label the core, 111In-doped iron oxide NPs were encapsulated inside PLGA-NPs during NP preparation, and the BSA coating was labelled by electrophilic substitution using 125I. After intravenous administration into rats, energy-discriminant SPECT resolved each radioisotope independently. Imaging revealed different fates for the core and coating, with a fraction of the two radionuclides co-localising in the liver and lungs for long periods of time after administration, suggesting that NPs are stable in these organs. Organ harvesting followed by gamma counting corroborated the SPECT results. The general methodology reported here represents an excellent alternative for visualising the degradation process of multi-labelled NPs in vivo and can be extended to a wide range of engineered NPs.

Colonization and bacteremia risk factors in parenteral nutrition catheterization.

AIMS: 1) To establish the relationship between the kind of microorganism that colonizes parenteral nutrition catheters and several risk factors related to catheterization and patient characteristics. 2) To investigate the risk factors associated to bacteremia episodes originated in these colonized catheters. METHOD: An observational, non-controlled, retrospective and cohorts study of the parenteral nutrition catheters implanted between 1988 and 1994 in our hospital. Risk factors were studied in 6 multiple-logistic regression models. RESULTS: 3632 catheters were studied. Incidences of colonization and bacteremia per 1000 days of catheterization were 17.56 and 3.93, respectively. Coagulase-negative staphyloccoci (CNS) were the most frequently isolated microorganisms. The colonization risk factors were: insertion site for all the microorganisms except fungi, catheterization time for CNS and fungi, hospitalization area, sex and age for CNS model, the existence of other infectious foci for Gram negative bacilli (GNB), S. aureus and other microorganisms, hypoalbuminemia for GNB model, and neoplasm for other microorganisms. The bacteremia risk factors were jugular insertion site, catheterization time greater than 10 days, catheter's hub colonization, and catheter colonization by gram-negative bacilli, fungi and S. aureus. CONCLUSION: Risk factors for catheter colonization vary depending on the microorganism which colonizes the catheter.

Serum albumin as indicator of clinical evolution in patients on parenteral nutrition. Multivariate study.

BACKGROUND AND AIMS: The aim of this study is to establish whether serum albumin concentration at the beginning of parenteral nutrition is related to morbidity and mortality. METHODS: In this cohort study spanning four years, a number of patients were classified into twelve groups, depending on their clinical status at the beginning of parenteral nutrition. Their serum albumin concentration and other clinical parameters were then measured and twelve multiple logistic regression models were thus generated in order to model the relationship between initial albumin concentration and risk of morbidity/mortality. RESULTS: 1953 (84%) of the 2321 patients studied were hypoalbuminemic. In six models, this condition was associated with a significant increase in the risk of nosocomial infection. However, no model could be associated to significant risk of renal failure, and only patients with previous hepatopathy were at risk for hepatic failure. In seven models, there was a significant increase in mortality. CONCLUSIONS: Serum albumin concentration at the beginning of parenteral nutrition is related to mortality and morbidity associated with nosocomial infection in some groups of the study.

The importance of clinical factors in parenteral nutrition-associated hypertriglyceridemia.

AIMS: The purpose of this study was to establish the relevance of several clinical factors associated with parenteral nutrition (PN) hypertriglyceridemia and to construct a predictive model for this complication. METHOD: This multicenter study included all patients with initial serum triglyceridemia <3 mmol and receiving a minimum of 7 days' PN therapy. The study ended for each patient when hypertriglyceridemia developed or PN was terminated. Two multivariate models were constructed, one to study the clinical factors and the second to predict plasma triglyceridemia. A total of 22 clinical factors studied as independent variables were included in the multiple-step regression models only when they showed a P-value over 0.1. Statistical significance was determined by the confidence interval of the odds ratio (OR) and the partial regression coefficient (b). RESULTS: The study included 260 patients from 14 hospitals. Lipid administration was 0.83+/-0.37 g/kg/day. Among the total, 68 patients (26.2%) showed hypertriglyceridemia. Variables included in both models were serum glucose (OR, 2.63; b, 0.06), renal failure (OR, 10.56; b, 1.70), corticoid administration >0.5 mg/kg (OR, 7.98; b, 0.97), pancreatitis (OR, 4.38; b, 0.64), sepsis (OR, 4.48; b, 0.24), lipids infused (OR, 3.03; b, 0.24) and heparin administration >3 mg/kg/day (OR, 0.11; b, -1.21). CONCLUSION: Although the rate of lipid infusion was low, certain clinical factors modified triglyceridemia. Nevertheless, relatively fast plasma clearance of lipids infused indicates that a reduction in lipid supply could be a quick, effective measure for controlling hypertriglyceridemia. Thus, careful monitoring of patients with clinical factors predicting risk in the model studied, with adjustment of lipid perfusion rates accordingly, is suggested to avoid hypertriglyceridemia.

Staphylococcus saprophyticus sepsis related to total parenteral nutrition admixtures contamination.

The aim of this study was to report an outbreak of sepsis related to contamination of total parenteral nutrition (TPN) admixtures with Staphylococcus saprophyticus. A total of four patients developed fever after administration of contaminated TPN. Results of cultures of blood, catheter hubs and tips, and TPN admixtures are presented. The strain responsible for the outbreak was able to grow in vitro in two common TPN formulations.

[Changes in the biochemical parameters during parenteral nutrition. The experience in Hospital de Bellvitge]. / Alteraciones en los parámetros bioquímicos durante la nutrición parenteral. Experiencia en el Hospital de Bellvitge.

The purpose of this study is to evaluate the modifications in biochemical parameters before and after the initiation of nutritional therapy, and to observe whether there is a relationship between the patient's development (exitus or improvement) and the presence of sepsis. The study was performed on 578 adults treated in our hospital from January 1988 to October 1989. The parameters analyzed were the following: glucose, triglycerides, total proteins, albumin, cholesterol, alkaline phosphatase, GOT, GPT, bilirubin, GGT, urea, urates, creatinine and electrolytes. The average initial values of each parameter were compared against those obtained after interrupting the PN by means of the Student t test. The results showed that within the parameters indicating the hepatic function, GGT and alkaline phosphatase were those that showed the most significant differences after ceasing the PN. Furthermore, the parameters indicating hepatic function and the electrolytes showed greater variations, regardless of the clinical evolution of the patient (improvement or exitus). The remainder of the parameters showed significant variations based on the clinical evolution.

[The bacteriological control of TPN mixtures at the Hospital de Bellvitge]. / Control bacteriológico de las mezclas de NPT en el Hospital de Bellvitge.

The complications of sepsis often make it necessary to suspend nutritional therapy. The origin of these is the nutritive mixture as well as the catheter connection and/or point where it has been inserted. The aim of this study is to show the need for bacteriological control of the whole process, in order to evaluate the effectiveness of the methods used, dilucidate the origin of the sepsis and establish an internal quality control. Study of different methods for bacteriological control of the nutritive mixtures, comparing them with the methods used in our Hospital, which is based on systematic culture of the mixtures, the collecting of samples after preparation and prior to perfusing the mixture through the patient, the performing of a further culture control and a bacteriological examination of the catheter. For this purpose, 28,501 nutritive mixtures were studied, corresponding to 1,782 patients. Of these, 185 samples were initially positive (0.65%) and only 59 samples showed positive cultures (0.21%). Of the 6 cases of sepsis discovered and confirmed by haemoculture, 5 corresponded to Enterobacter cloacae and 1 to Klebsiella pneumoniae.

[Bacteriologic control of total parenteral nutrition formulations at the Bellvitge Hospital]. / Control bacteriológico de las mezclas de NPT en el Hospital de Bellvitge.

Septic complications often lead to halting nutritional parenteral therapy. In general, the source of infection lies in the mixture, the connection and/or point of catheter insertion. The objective of this study is to show the need for bacteriological control throughout the parenteral nutrition process in order to assess the efficacy of the methods used, discover the source of infection and establish an in-house quality control. Different methods for bacteriological control of parenteral nutrition mixtures are studied and are compared with the method used at our hospital which is based on routine culture sampling after the mixture is prepared and before it is perfused, on repeating bacteriological control cultures and on performing bacteriological assessments of the catheter. In order to achieve this goal, 28.501 nutritional parenteral samples from 1,782 patients were studied. Only 185 (0.65%) samples were originally positive, and only 59 of them (0.21%) remained positive following a verification culture. Of the 6 culture-verified septic cases, 5 corresponded to Enterobacter cloacae and 1 to Klebsiella pneumoniae.

[A comparative study of hepatic cholestasis after infusion of long chain triglycerides and a mixture of medium and long chain triglycerides]. / Estudio comparativo de la colestasis hepática entre la infusión de triglicéridos de cadena larga y mezcla de triglicéridos de cadena media y larga.

A randomized, double blind prospective study made on surgical patients who required parenteral nutrition during a 10-day period, with complete fasting. The patients were required to show a normal hepatic function measured by gamma-GT, alkaline phosphatase (FA), normal bilirubin and ALT. The evolution of the cholestasis parameters was observed on days 0, 1, 3, 8 and 10. An increase in gamma-GT was observed in the groups. This was much greater in the group with LCT (p<0.005) on the tenth day than in the MCT/LCT group. FA increased only in the LCT group, and was statistically significant (p<0.001) on the tenth day compared with the MCT/LCT group.

Positron emission tomograghy with [¹³N]ammonia evidences long-term cerebral hyperperfusion after 2h-transient focal ischemia.

BACKGROUND AND PURPOSE: It is well known that after cerebral ischemia, brain suffers blood flow changes over time that have been correlated with inflammation, angiogenesis and functional recovery processes. Nevertheless, post-ischemic spatiotemporal changes of brain perfusion have not been fully investigated to date. Here we tested whether PET with [¹³N]ammonia would evidence the perfusion changes presented by different brain regions in an experimental model of brain ischemia. EXPERIMENTAL PROCEDURES: Seven rats were subjected to a 2-h transient middle cerebral artery occlusion with reperfusion. PET studies were performed longitudinally using [¹³N]ammonia at 1, 3, 7, 14, 21 and 28 days after cerebral ischemia. RESULTS: In vivo PET imaging showed a significant increase in [¹³N]ammonia uptake at 7 days after cerebral ischemia with respect to one day after the occlusion in the cerebral territory irrigated by the MCA in both the ischemic and contralateral hemispheres. This increase was followed by a return to control values at day 28 after ischemia onset. Brain regions located both inside and outside the primary infarct areas showed similar perfusion changes after cerebral ischemia. CONCLUSIONS: [¹³N]ammonia shows hemodynamic changes after stroke involving hyperperfusion that might be related to angiogenesis and functional recovery. Long-term blood hyperperfusion is found both in ischemic and remote areas to infarction. These results may contribute to a better understanding of the evolution of cerebral ischemic lesion in animal models.