Mechanistic insights into the aetiology of post-prandial decline in testosterone in reproductive-aged men.

Obesity is known to be associated with impaired testicular function potentially resulting in androgen deficiency and subfertility. While the underlying cause of obesity-related male hypogonadism is multi-factorial, here, we investigated the impact of dietary fat on testicular endocrine function. Ingestion of a high-fat "fast food" mixed meal, a common practice for obese men, produced a 25% fall in serum testosterone within an hour of eating, with levels remaining suppressed below fasting baseline for up to 4 hr. These changes in serum testosterone were not associated with any significant changes in serum gonadotrophins. The nadir in serum testosterone preceded the post-prandial increase in serum IL-6/IL-17 by several hours, suggesting that inflammation was unlikely the cause. Furthermore, intravenous administration of fat (Intralipid) had no impact on testosterone levels, while an identical oral dose of fat did suppress testosterone. These results suggest that fat does not directly impair Leydig cell function, but rather the passage of fat through the intestinal tract elicits a response that indirectly elicits a post-prandial fall in testosterone.

Multi-component lipid emulsion vs soy-based lipid emulsion for very low birth weight preterm neonates: A pre-post comparative study.

OBJECTIVE: To examine the effectiveness of soybean oil-medium chain triglycerides-olive oil-fish oil lipid emulsion (SMOF-LE) on clinical outcomes of very-low-birth-weight neonates. STUDY DESIGN: We conducted a pre-post comparative study of very-low-birth-weight neonates, dividing them according to lipid emulsion received: Intralipid (soy-based; n = 680) or SMOF-LE (n = 617). Primary outcomes were mortality, chronic lung disease, severe retinopathy, infection, and necrotising enterocolitis. Secondary outcomes were cholestasis, osteopenia, time to full feeds, and time to regain birthweight. RESULTS: Baseline characteristics between groups were comparable. Primary outcomes did not differ significantly between groups, although any retinopathy was significantly lower in the SMOF-LE group. SMOF-LE group had lower odds of cholestasis, osteopenia, and lipid interruption, and reduced times to full feeds and to regain birthweight. CONCLUSIONS: Compared with Intralipid, SMOF-LE was not associated with differences in mortality and major morbidities but was associated with lower odds of any retinopathy, cholestasis, and osteopenia; and improved lipid tolerance.

Lipid emulsions for parenterally fed term and late preterm infants.

BACKGROUND: Lipid emulsions (LE) form a vital component of infant nutrition for critically ill, late preterm or term infants, particularly for those with gastrointestinal failure. Conventionally used soybean oil-based LE (S-LE) have high polyunsaturated fatty acid (PUFA) content and phytosterols, which may contribute to adverse effects including parenteral nutrition-associated liver disease (PNALD). OBJECTIVES: To compare the safety and efficacy of all LE for parenteral nutrition (PN) in term and late preterm infants (between 34 weeks' gestation and 36 weeks' and six days' gestation) with or without surgical conditions or PNALD within first six months of life, using all possible direct comparisons. SEARCH METHODS: We used the standard search strategy of Cochrane Neonatal to search the Cochrane Central Register of Controlled Trials (CENTRAL 2018, Issue 5), MEDLINE (1946 to 18 June 2018), Embase (1974 to 18 June 2018), CINAHL (1982 to 18 June 2018), MIDRIS (1971 to 31 May 2018), conference proceedings, trial registries (ClinicalTrials.gov and the WHO's Trials Registry), and the reference lists of retrieved articles for randomised controlled trials and quasi-randomised trials. SELECTION CRITERIA: Randomised or quasi-randomised controlled studies in term and late preterm infants, with or without surgical conditions or PNALD. DATA COLLECTION AND ANALYSIS: Data collection and analysis conformed to the methods of Cochrane Neonatal. We used the GRADE approach to assess the quality of evidence for important outcomes in addition to reporting the conventional statistical significance of results. MAIN RESULTS: The review included nine randomised studies (n = 273). LE were classified in three broad groups: 1. all fish oil-containing LE including pure fish oil (F-LE) and multisource LE (e.g. medium-chain triglycerides (MCT)-olive-fish-soybean oil-LE (MOFS-LE), MCT-fish-soy oil-LE (MFS-LE) and olive-fish-soy-LE (OFS-LE)); 2. conventional pure S-LE; 3. alternative-LE (e.g. MCT-soy-LE (MS-LE), olive-soy-LE (OS-LE) and borage oil-based LE).We considered four broad comparisons: 1. all fish oil LE versus non-fish oil LE (6 studies; n = 182); 2. fish oil LE versus another fish oil LE (0 studies); 3. alternative-LE versus S-LE (3 studies; n = 91); 4. alternative-LE versus another alternative-LE (0 studies) in term and late preterm infants (0 studies), term and late preterm infants with surgical conditions (7 studies; n = 233) and term and late preterm infants with PNALD/cholestasis (2 studies; n = 40).PNALD/cholestasis was defined as conjugated bilirubin (Cbil) 2 mg/dL or greater and resolution of PNALD/cholestasis as Cbil less than 2 mg/dL. We put no restriction on timing of PNALD detection. There was heterogeneity in definitions and time points for detecting PNALD in the included studies.We found one study each in surgical infants and in infants with cholestasis, showing no evidence of difference in incidence or resolution of PNALD/cholestasis (Cbil cut-off: 2 mg/dL) with use of fish oil-containing LE compared to S-LE.We considered an outcome allowing for any definition of PNALD (different Cbil cut-off levels). In infants with surgical conditions and no pre-existing PNALD, meta-analysis showed no difference in the incidence of PNALD/cholestasis (any definition) with use of fish oil-containing LE compared to S-LE (typical risk ratio (RR) 1.20, 95% confidence interval (CI) 0.38 to 3.76; typical risk difference (RD) 0.03, 95% CI -0.14 to 0.20; 2 studies; n = 68; low-quality evidence). In infants with PNALD/cholestasis (any definition), use of fish oil-LEs was associated with significantly less cholestasis compared to the S-LE group (typical risk ratio (RR) 0.54, 95% confidence interval (CI) 0.32 to 0.91; typical risk difference (RD) -0.39, 95% CI -0.65 to -0.12; number needed to treat for additional beneficial outcome (NNTB) 3, 95% CI 2 to 9; 2 studies; n = 40; very low-quality evidence). This outcome had very low number of participants from two small studies with differences in study methodology and early termination in one study, which increased uncertainty about the effect estimates.One study in infants with cholestasis reported significantly better weight gain with a pure fish oil LE compared to a 10% S-LE (45 g/week, 95% CI 15.0 to 75.0; n = 16; very low-quality evidence). There were no significant differences in growth parameters in studies with surgical populations.For the secondary outcomes, in infants with cholestasis, one study (n = 24) reported significantly lower conjugated bilirubin levels but higher gamma glutamyl transferase levels with MOFS-LE (SMOFlipid) versus S-LE (Intralipid) and another study (n = 16), which was terminated early, reported significantly higher rates of rise in alanine aminotransferase (ALT) and conjugated bilirubin levels in the S-LE group compared to pure F-LE (Omegaven).In surgical infants, two studies each reported on hypertriglyceridaemia and Cbil levels with one study in each outcome showing significant benefit with use of a F-LE and the other study showing no difference between the groups. Meta-analysis was not performed for either of these outcomes as there were only two studies showing conflicting results with high heterogeneity between the studies.There was no evidence of differences in death, sepsis, alkaline phosphatase and ALT levels in infants with surgical conditions or cholestasis (very low-quality evidence).One study reported neurodevelopmental outcomes at six and 24 months in infants with surgical conditions (n = 11) with no evidence of difference with use of pure F-LE versus S-LE. Another study in infants with cholestasis (n = 16) reported no difference in head growth velocity between pure F-LE versus S-LE.GRADE quality of evidence ranged from low to very low as the included studies were small single-centre studies. Three of the six studies that contributed data to the review were terminated early for various reasons. AUTHORS' CONCLUSIONS: Based on the current review, there is insufficient data from randomised studies to determine with any certainty, the potential benefit of any LE including fish oil-containing LEs over another LE, for prevention or resolution of PNALD/cholestasis or any other outcomes in term and late preterm infants with underlying surgical conditions or cholestasis. There were no studies in infants without surgical conditions or cholestasis.Further research is required to establish role of fish oil or lipids from other sources in LEs to improve PNALD/cholestasis, and other clinical outcomes in parenterally fed term and late preterm infants.

Propofol use in children with allergies to egg, peanut, soybean or other legumes.

Propofol is the most commonly administered intravenous agent for anaesthesia in children. However, there are concerns that the emulsified preparation may not be safe in children with an allergy to egg, peanut, soybean or other legumes. We conducted a retrospective study of children with immunologically confirmed egg, peanut, soybean or legume allergy and who underwent general anaesthesia at Princess Margaret Hospital for Children between 2005 and 2015. We extracted details regarding allergy diagnosis, each anaesthetic administered and any adverse events or signs of an allergic reaction in the peri-operative period. A convenience sample of patients without any known food allergies was identified from our prospective anaesthesia research database and acted as a control group. We identified 304 food-allergic children and 649 procedures where propofol was administered. Of these, 201 (66%) had an egg allergy, 226 (74%) had a peanut allergy, 28 (9%) had a soybean allergy and 12 (4%) had a legume allergy. These were compared with 892 allergy-free patients who were exposed to propofol. In 10 (3%) allergy patients and 124 (14%) allergy-free patients, criteria for a possible allergic reaction were met. In nine of the food-allergic children and in all the controls valid non-allergic explanations for the clinical symptoms were found. One likely mild allergic reaction was experienced by a child with a previous history of intralipid allergy. We conclude that genuine serious allergic reaction to propofol is rare and is not reliably predicted by a history of food allergy.

Encapsulation of babchi essential oil into microsponges: Physicochemical properties, cytotoxic evaluation and anti-microbial activity.

Babchi essential oil (BEO) is a valuable essential oil reported to possess a variety of biological activities such as antitumor, anti inflammatory, immunomodulatory, antioxidant, antifungal and antibacterial properties. Due to its anti-microbial properties, this oil possesses an immense potential for the treatment of dermatological disorders. Further, it has minimal tendency to develop resistance, a common issue with most of the antibiotics. However, its highly viscous nature and poor stability in the presence of light, air and high temperature, limits its practical applications. To surmount these issues, this research aims to encapsulate BEO in ethyl cellulose (EC) microsponges for enhanced stability, antibacterial effect and decreased dermal toxicity. The quasi emulsion solvent evaporation technique was used for fabrication of the BEO microsponges employing EC as polymer, polyvinyl alcohol (PVA) as stabilizer and dichloro methane (DCM) as solvent. The effect of formulation variables such as the amount of EC and PVA were also investigated. The prepared microformulations were evaluated for production yield, encapsulation efficiency, particle size and in vitro release. In vitro cytotoxicity was also checked to assess dermal safety of BEO microsponges. Results revealed that all the dispersions were in micro size range (20.44 ± 3.13 µm to 41.75 ± 3.65 µm), with good encapsulation efficiency (87.70 ± 1.20% of F2) and controlled release profile (cumulative drug release 73.34 ± 1.76%). Field emission scanning electron microscopy results showed that the microsponges possessed a spherical uniform shape with a spongy structure. Results of cytotoxicity study indicated that the prepared microsponges were safer on dermal cells in comparison to pure BEO. The optimized formulation was also evaluated for in vitro antimicrobial assay against dermal bacteria like Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which confirmed their enhanced antibacterial activity. Furthermore, the results of photostability and stability analysis indicated improved stability of BEO loaded microsponges. Hence, encapsulation of BEO in microsponges resulted in efficacious carrier system in terms of stability as well as safety of this essential oil alongwith handling benefits.

Intralipid® may represent a new hope for patients with reproductive failures and simultaneously an over-immune endometrial activation.

PROBLEM: Continuous failures to achieve a pregnancy despite effective embryo transfers is extremely distressing for couples. In consequence, many adjuvant therapies to IVF have been proposed to achieve an "ideal" immune environment. We here focus on Intralipid® therapy (IL) reported to have immunosuppressive properties on NK cells. METHOD OF STUDY: 94 patients exhibited an immune profile of endometrial over-immune activation and an history of repeated implantation failures despite multiple embryos transfers (RIF). They received a slow perfusion of Intralipid®. We here report the live birth rate following the procedure at the next embryo transfer. To get new insight on its mechanism of action, a second immune profiling had been performed under Intralipid® before the embryo transfer. RESULTS: The live birth rate of the RIF cohort treated with Intralipid® reached 54% (51/94) at the next embryo transfer. In patients successfully pregnant under Intralipid® who benefitted of a test of sensibility before the embryo transfer, we observed a significant decrease of the three biomarkers used to diagnose the over-immune endometrial activation (CD56 cells; IL-18/TWEAK, IL-14/FN-14). CONCLUSIONS: Double blind placebo versus Intralipid® studies should be conducted. Intralipid® may be an option to explore in RIF patients who exhibit an over-immune activation of uNK cells.

Olive Oil and Soybean Oil Based Intravenous Lipid Emulsions, Liver Biochemistry and Clinical Outcomes.

Intravenous lipid emulsions are an essential component of parenteral nutrition (PN). Omega-6 reducing strategies may improve outcomes, including reduced PN associated liver disease, however evidence to support this recommendation is insufficient. The primary objective was to compare serum alkaline phosphatase (ALP), among patients provided with either soybean oil (Intralipid) or predominantly olive oil (Clinoleic) lipid emulsions. In this quasi-experimental study, we reviewed the medical records of surgical and medical adult patients who received lipid emulsions for at least seven consecutive days. Among the 206 patients (110-Intralipid, 96-Clinoleic) there was no significant difference in ALP and remaining liver function tests within 2 weeks of PN therapy initiation between groups, even after control for lipid doses. Macronutrient dosing was similar. Triglyceride level was higher by 0.7 mmol/L in the Clinoleic group; confidence interval 0.21 to 1.1; p = 0.004. The 30-day mortality, length of hospital stay, and proportion of patients admitted to intensive care were not significantly different. The Clinoleic group had a higher infection rate (36% vs. 22%, p = 0.031) and longer intensive care stays (p = 0.045). Well-designed randomized clinical trials comparing these lipid emulsions are necessary to confirm Intralipid superiority over Clinoleic in relation to infections and serum triglycerides.

Impact of SMOFLipid on Pulmonary Alveolar Development in Newborn Guinea Pigs.

BACKGROUND: Parenteral nutrition (PN) is associated with bronchopulmonary dysplasia in premature infants. In animals, PN leads to alveolar loss following stimulation of apoptosis by oxidative stress (oxidized redox potential). Peroxides and aldehydes generated in PN can induce hypo-alveolarization. The implication of peroxides, which is reduced by light protection, is demonstrated. The implication of aldehydes from omega-6 fatty acids oxidation is expected. The hypothesis is that composition and light exposure of PN influences bronchopulmonary dysplasia development. Since SMOFLipid (SMOF) contains a lower amount of omega-6 fatty acids than Intralipid (IL), the aim was to compare, the impacts of PN compounded with SMOF or IL, photo-protected or not, on alveolar development. MATERIALS AND METHODS: Three-day-old Guinea pigs received PN, photo-protected or not, made with SMOF or IL through a jugular vein catheter. After 4 days, lungs were sampled for determinations of redox potential of glutathione, apoptosis (caspase-3, caspase-8, and caspase-9) and alveolarization index (histology: number of intercepts/mm). RESULTS: Compared with IL, SMOF induces a greater oxidation of redox potential (-200 ± 1 versus [vs] -205 ± 1 mV), apoptosis (caspase-3: 0.27 ± 0.04 vs 0.16 ± 0.02; caspase-9: 0.47 ± 0.03 vs 0.30 ± 0.03), and a lower alveolarization index (27.2 ± 0.8 vs 30.0 ± 0.9). Photo-protection prevented activation of caspase-9 and was statistically without effect on redox potential, caspase-3, and alveolarization index. CONCLUSION: In our model, SMOF is pro-oxidant and induces hypo-alveolarization following exaggerated apoptosis. These results highlight the need for further studies before introducing SMOFLipid in standard neonatal care.

Inpatient outcomes of preterm infants receiving ω-3 enriched lipid emulsion (SMOFlipid): an observational study.

Neonatal units have started to switch from using conventional soy-based to alternate lipid emulsions, like SMOFlipid. SMOFlipid has been associated with an improvement in biochemical parameters and delays progression of parenteral nutrition-associated liver disease (PNALD). This retrospective epoch study aimed to compare clinically relevant neonatal outcomes in preterm infants (< 32 weeks), receiving SMOFlipid versus Intralipid. We compared clinical outcomes in two epochs-epoch 1 (Intralipid, October 2013-June 2015) versus epoch 2 (SMOFlipid, July 2015-March 2017). Primary outcome studied was mortality and rates of severe neonatal morbidities. Univariate and multivariate regression was conducted to determine risk for mortality and PNALD. A total of 222 infants (epoch 1, 123 versus epoch 2, 99) were included in the study. A higher incidence of late onset sepsis (56 versus 30%, p < 0.005) was observed in epoch 1. There was no significant difference in mortality or rates of any other severe neonatal morbidity. The type of lipid emulsion did not have a significant effect on mortality or PNALD on regression analysis. CONCLUSION: Use of SMOFlipid as the primary lipid emulsion seems to have minimal effect on rates of clinically important neonatal outcomes; however, long-term effects need to be further evaluated. What is Known: • Many neonatal units have started replacing traditional soy-based lipid formulations with SMOFlipid (ω-3 enriched lipid emulsion), as the primary lipid component in parenteral nutrition for preterm infants. • While there is evidence associating improved liver function and balanced essential fatty acid levels in infants receiving SMOFlipid, there is a lack of evidence evaluating relevant clinical outcomes in infants receiving SMOFlipid versus traditional lipid formulations. What is New: • The influence of SMOFlipid on a series of clinical outcomes in an at-risk preterm population is presented. • SMOFlipid appears to be well tolerated in preterm infants with minimal side effects, and some growth benefits seen.

Long-term Exposure of Children to a Mixed Lipid Emulsion Is Less Hepatotoxic Than Soybean-based Lipid Emulsion.

Lipid emulsions have been associated with liver injury. Newer mixed emulsions (ML), such as SMOFlipid (Fresenius Kabi, Germany), are thought to be more hepatoprotective than soybean-based emulsions (SL), such as Intralipid (Baxter). Pediatric studies comparing long-term use between the 2 are limited. This study compares the severity of hepatic injury between a prospective cohort of hospitalized children on ML (n = 20) and a historical age- and diagnosis-matched cohort of hospitalized children on SL (n = 20). Median exposure to ML and SL were 10 versus 6 weeks (P = 0.030), respectively, at similar median lipid doses (2.2 vs 2.1 g ·â€Škg ·â€Šday). Using a generalized estimating equations approach, conjugated bilirubin trajectory was found to be lower in patients on ML compared with SL (P < 0.001), suggesting that prolonged exposure (≥4 weeks) to ML is associated with decreased liver injury compared with SL in hospitalized children.

Safety against nephrotoxicity in paclitaxel treatment: Oral nanocarrier as an effective tool in preclinical evaluation with marked in vivo antitumor activity.

Oral paclitaxel (PTXL) formulations freed from cremophor® EL (CrEL) is always in utmost demand by the cancerous patients due to toxicities associated with the currently marketed formulation. In our previous investigation [Int. J. Pharm. 2014; 460:131], we have developed an oral oil based nanocarrier for the lipophilic drug, PTXL to target bioavailability issue and patient compliance. Here, we report in vivo antitumor activity and 28-day sub-chronic toxicity of the developed PTXL nanoemulsion. It was observed that the apoptotic potential of oral PTXL nanoemulsion significantly inhibited the growth of solid tumor (59.2 ± 7.17%; p < 0.001) without causing any explicit toxicity. The 6.5 mg/kg and 3 mg/kg oral PTXL nanoemulsion dose did not cause any notable alteration in haematological, biochemical/structural characteristics during 28-day sub-chronic toxicity studies in the experimental mice. Whereas, the toxicity of 12.8 mg/kg body weight dose showed decrease in RBC, haemoglobin and neutrophil counts. In contrast, marketed PTXL (Taxol®) was found to be comparatively more toxic to the experimental animals. Taxol® treatment resulted glomerulonephritis in histopathological examination, which could be correlated with increased level of creatinine and associated nephrotoxicity. This investigations conclude that the developed oral nanoemulsion presents a viable therapeutics bio-system to step towards clinical application as well as substitute CrEL based PTXL formulations.

Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in Caco-2 cells.

Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide (LPS) in patients with total parenteral nutrition, but the appropriate preventative treatment is currently limited. Recently, sodium butyrate (NaBut) has been demonstrated to regulate the expression of P-gp. Therefore, this study aimed to address whether treatment with NaBut could attenuate SOLE-induced increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2 cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of P-gp was significantly attenuated by co-incubation with NaBut. Nuclear recruitment of FOXO 3a in response to NaBut was involved in P-gp regulation. Transport studies revealed that SOLE-induced increase in permeability of LPS was significantly attenuated by co-incubation with NaBut. Collectively, our results suggested that NaBut may be a potentially useful medication to prevent SOLE-induced increase in intestinal permeability of LPS.

Effect of a p38 MAPK inhibitor on FFA-induced hepatic insulin resistance in vivo.

The mechanisms whereby prolonged plasma free fatty acids elevation, as found in obesity, causes hepatic insulin resistance are not fully clarified. We herein investigated whether inhibition of p38 mitogen-activated protein kinase (MAPK) prevented hepatic insulin resistance following prolonged lipid infusion. Chronically cannulated rats were subdivided into one of four intravenous (i.v.) treatments that lasted 48 h: Saline (5.5 µl min(-1)), Intralipid plus heparin (IH, 20% Intralipid+20 U ml(-1) heparin; 5.5 µl min(-1)), IH+p38 MAPK inhibitor (SB239063) and SB239063 alone. During the last 2 h of treatment, a hyperinsulinemic (5 mU kg(-1) min(-1)) euglycemic clamp together with [3-(3)H] glucose methodology was carried out to distinguish hepatic from peripheral insulin sensitivity. We found that SB239063 prevented IH-induced hepatic insulin resistance, but not peripheral insulin resistance. SB239063 also prevented IH-induced phosphorylation of activating transcription factor 2 (ATF2), a marker of p38 MAPK activity, in the liver. Moreover, in another lipid infusion model in mice, SB239063 prevented hepatic but not peripheral insulin resistance caused by 48 h combined ethyloleate plus ethylpalmitate infusion. Our results suggest that inhibition of p38 MAPK may be a useful strategy in alleviating hepatic insulin resistance in obesity-associated disorders.

[Rats hyperuricemia model established by lipid emulsion simulating irregular of diet].

Due to the irregular of diet and overfeeding greasy and surfeit flavor closely associated with hyperuricemia disease, the lipid emulsion containing high cholesterol was used to model. To obtain a more stable and sustained animal model for the efficacy evaluation of traditional Chinese herbs, we observed the influence on the serum uric acid of rat induced by the lipid emulsion compared with high purine diet. 36 SD male rats were randomized to the normal control group, high purine diet group and lipid emulsion group respectively. The general behavior, body weight and daily food intake of rats were observed. The orbital blood was taken to separate into the serum and 24 hours urine was collected. The serum indexes such as UA, BUN, Cr, ALT, AST, TC, TG, LDL-c were determined every 2 weeks, and XOD, ADA enzyme activity were determined at the 4th week. The urine indexes such as UA, Cr and Cua/Ccr were determined at the 4th week. After stopping modeling, the serum UA were determined two weeks and four weeks later respectively. At the 2nd week, the body weight and daily food intake of rats in the lipid emulsion group reduced significantly, and the level of serum UA, BUN, Cr, TC, LDL-c, ATL, AST raised significantly meanwhile TG reduced. At the 4th week, the serum UA in high purine diet group did not raise, and the serum XOD raised obviously while ADA did not; the serum UA in lipid emulsion group was higher significantly, and the serum XOD and ADA raised while Cua/Ccr reduced obviously. At the 6th weeks, the serum UA in both the high purine diet group and lipid emulsion group raised obviously. After stopping modeling, the serum UA in lipid emulsion group still maintained a high level at the 2nd week and back to the normal level at the 4th week. Compared with high purine diet, the hyperuricemia model induced by lipid emulsion forms earlierand more stable. It maybe has great value to study the pharmacodynamics of traditional Chinese medicine treatment to hyperuricemia disease. Its mechanism may be related to increasing XOD and ADA enzyme activity which can promote uric acid synthesis, meanwhile inhibiting of uric acid excretion.

Damaging Effects of Total Parenteral Nutrition Formula on Vascular Endothelium.

OBJECTIVES: Sepsis in one of the most serious complications that can occur during total parenteral nutrition (TPN) procedures. In this experimental study, we investigated the effects of TPN, with or without lipid emulsion, on vascular endothelial damage. METHODS: In total, 50 rabbits were used, divided into 5 groups of 10 each. TPN with lipids (group 1), TPN without lipids (group 2), and 0.09% saline (group 3) were given for 10 days via a central venous catheter. Group 4 received no treatment other than placement of a central venous catheter for 10 days. Group 5 was a control group. At the end of day 10, rabbits were sacrificed and tissue samples of liver, kidney, and inferior vena cava were prepared and examined by immunohistochemical methods for vascular cellular adhesion molecule (VCAM)-1 expression. RESULTS: In tissue sections of liver, kidney, and inferior vena cava, VCAM-1 activity was increased prominently in TPN with and without lipids compared with the control group. VCAM-1 activity in the TPN with lipids group was decreased versus the TPN without lipids group (P > 0.05). CONCLUSIONS: The TPN procedure results in vascular endothelial cell damage not only in the vein where the solution is introduced but also in other parts of the vascular system. Even if it is not statistically significant, lipids in the TPN formula may decrease this endothelial cell damage, as shown by immunohistochemistry.

Blood lipids affect rat islet blood flow regulation through ß3-adrenoceptors.

Pancreatic islet blood perfusion varies according to the needs for insulin secretion. We examined the effects of blood lipids on pancreatic islet blood flow in anesthetized rats. Acute administration of Intralipid to anesthetized rats increased both triglycerides and free fatty acids, associated with a simultaneous increase in total pancreatic and islet blood flow. A preceding abdominal vagotomy markedly potentiated this and led acutely to a 10-fold increase in islet blood flow associated with a similar increase in serum insulin concentrations. The islet blood flow and serum insulin response could be largely prevented by pretreatment with propranolol and the selective ß3-adrenergic inhibitor SR-59230A. The nitric oxide synthase inhibitor N(G)-nitro-l-arginine methyl ester prevented the blood flow increase but was less effective in reducing serum insulin. Increased islet blood flow after Intralipid administration was also seen in islet and whole pancreas transplanted rats, i.e., models with different degrees of chronic islet denervation, but the effect was not as pronounced. In isolated vascularly perfused single islets Intralipid dilated islet arterioles, but this was not affected by SR-59230A. Both the sympathetic and parasympathetic nervous system are important for the coordination of islet blood flow and insulin release during hyperlipidemia, with a previously unknown role for ß3-adrenoceptors.

Fish oil-based lipid emulsions in the treatment of parenteral nutrition-associated liver disease: an ongoing positive experience.

We previously reported the beneficial effect of fish oil-based lipid emulsions (FOLEs) as monotherapy in the treatment of parenteral nutrition-associated liver disease (PNALD). In this report, we share our ongoing experience at Texas Children's Hospital, Houston, Texas in the use of FOLE in treatment of PNALD as presented at the 2013 Experimental Biology meeting. We describe the findings of a single center, prospective, observational study of infants <6 mo of age with PNALD who received parenteral FOLE as monotherapy. A total of 97 infants received FOLE under the compassionate-use protocol for the treatment of PNALD. Eighty-three (86%) survived with resolution of cholestasis and 14 (14%) died. The median conjugated bilirubin (CB) concentration at the initiation of FOLE therapy was 4.8 mg/dL (range 2.1-26). The median time to resolution of cholestasis was 40 d (range 3-158). Compared with infants with mild cholestasis (CB of 2.1-5 mg/dL at the initiation of FOLE), nonsurvivors were significantly more premature and took longer to resolve their cholestasis. Gestational age at birth correlated inversely with CB at the beginning of FOLE and peak CB. Infants with an initial CB >10 mg/dL had a higher mortality rate than infants with an initial CB <5 mg/dL (35% vs. 6%; P < 0.05). Our experience with the use of FOLE in PNALD continues to be encouraging. Prematurity continues to be a major determinant in mortality and severity of cholestasis. This calls for further controlled studies designed to optimize dose and timing of intervention in the use of FOLE in neonates.

An update on safety and immunogenicity of vaccines containing emulsion-based adjuvants.

With the exception of alum, emulsion-based vaccine adjuvants have been administered to far more people than any other adjuvant, especially since the 2009 H1N1 influenza pandemic. The number of clinical safety and immunogenicity evaluations of vaccines containing emulsion adjuvants has correspondingly mushroomed. In this review, the authors introduce emulsion adjuvant composition and history before detailing the most recent findings from clinical and postmarketing data regarding the effects of emulsion adjuvants on vaccine immunogenicity and safety, with emphasis on the most widely distributed emulsion adjuvants, MF59® and AS03. The authors also present a summary of other emulsion adjuvants in clinical development and indicate promising avenues for future emulsion-based adjuvant development. Overall, emulsion adjuvants have demonstrated potent adjuvant activity across a number of disease indications along with acceptable safety profiles.

Alternative lipid emulsions in the critically ill: a systematic review of the evidence.

PURPOSE: Parenteral lipid emulsions (LEs) are commonly rich in long-chain triglycerides derived from soybean oil (SO). SO-containing emulsions may promote systemic inflammation and therefore may adversely affect clinical outcomes. We hypothesized that alternative oil-based LEs (SO-sparing strategies) may improve clinical outcomes in critically ill adult patients compared to products containing SO emulsion only. The purpose of this systematic review was to evaluate the effect of parenteral SO-sparing strategies on clinical outcomes in intensive care unit (ICU) patients. METHODS: We searched computerized databases from 1980 to 2013. We included randomized controlled trials (RCTs) conducted in critically ill adult patients that evaluated SO-sparing strategies versus SO-based LEs in the context of parenteral nutrition. RESULTS: A total of 12 RCTs met the inclusion criteria. When the results of these RCTs were statistically aggregated, SO-sparing strategies were associated with clinically important reductions in mortality (risk ratio, RR 0.83; 95 % confidence intervals, CI 0.62, 1.11; P = 0.20), in duration of ventilation (weighted mean difference, WMD -2.57; 95 % CI -5.51, 0.37; P = 0.09), and in ICU length of stay (LOS) (WMD -2.31; 95 % CI -5.28, 0.66; P = 0.13) but none of these differences were statistically significant. SO-sparing strategies had no effect on infectious complications (RR 1.13; 95 % CI 0.87, 1.46; P = 0.35). CONCLUSION: Alternative oil-based LEs may be associated with clinically important reductions in mortality, duration of ventilation, and ICU LOS but lack of statistical precision precludes any clinical recommendations at this time. Further research is warranted to confirm these potential positive treatment effects.