Plasma Citrulline : a New Marker of Gut Epithelium Alteration in Obese Patients?

Objectives: In the last decade gut microbial diversity was associated with the pathogenesis of obesity in humans. Plasma citrulline was a simple and accurate biomarker for the severity of intestinal failure and was associated with short bowel syndrome and alteration of gut permeability, being developed as an alternative to D-xylose tolerance test for the diagnosis of an abnormal small intestinal absorption of nutrients. This study was performed to ascertain whether obesity might be associated with dysregulation of epithelial gut function. Methods: Fifteen obese individuals (5 M/10 F; BMI 37.4 \ub1 6.1 Kg/m2; 42 \ub1 6 yrs) and 15 healthy gender- and age-matched controls (6 M/9 F BMI: 22.7 \ub1 2.1 Kg/m2; 39 \ub1 7 yrs) underwent D-xylose load (25 g) and plasma citrulline, plasma insulin, glucose and lipid profile testing. Results: Plasma citrulline was significantly lower in the obese group (p = 0.045) with respect to controls, whilst total cholesterol, LDL and tryglicerides concentration, insulin level and HOMA-IR were significantly higher in obese patients. In contrast, after D-xylose load no difference in serum xylose was found between the two groups (p = ns). Conclusions: Obese patients show a decreased citrulline concentration with respect to lean subjects. Since citrulline is a known marker of intestinal health, alterations in the gut epithelium are likely to be associated with the obesity syndrome. We propose to measure citrulline level in obese patients on a routine basis

Plasma mitomycin C concentrations determined by HPLC coupled to solid-phase extraction

The aim of this study was to set up a method for quantification of plasma mitomycin C (MMC) concentrations during intravesical chemotherapy delivered in the presence of local bladder hyperthermia (HT). In comparison with existing methods, this assay, characterized by relative simplicity and efficiency, resulted in the facilitation of performance with nondedicated instrumentation or nonspecialized staff. Purification from plasma matrix was carried out by solid-phase extraction under vaccuum. The purified drug was then collected directly into the vials of the HPLC autosampler. Chromatographic analysis was performed on a reversed-phase C18 column with water:acetonitrile (85:15 by vol) as the mobile phase and the UV detector set at 365 nm. The use of porfiromycin as internal standard provided a method with good within-day precision (CV 6.0% at 5 micrograms/L, n = 6), linearity (0.5-50 micrograms/L), and specificity. The lower limit of detection (< or = 0.5 microgram/L) proved to be suitable for plasma pharmacokinetics monitoring in two tested patients treated with MMC + HT for superficial bladder cancer

Dimethylarginines in critically ill patients with severe sepsis or septic shock

Objective:We investigated the trend of asymmetric dimethylarginine (ADMA) and symmetryc dimethyarginine (SDMA) in patients with severe sepsis and septic shock, and the relationship between dymethylarginines, organ failure, sepsis status and intensive care unit (ICU) mortality. Design: A prospective observational study carried out in three general adults Italian ICUs. Patient: Consecutive patients with severe sepsis or septic shock admitted to ICUs between December 2004 and March 2007. Methods: Plasma ADMA and SDMA were determined immediately after enrolment and on the third, sixth and twelfth days. Organ failure score, sepsis status, standard blood parameters and ICU outcome were collected. Resul\uc3\ub2ts: Twenty-nine consecutive patients were enrolled. ADMA and SDMA were higher in patients than in healthy volunteers. Sixteen patients who suffered from septic shock during ICU stay had a higher avarage value of daily ADMA and SDMA. ADMA was significantly related to arterial pH level, daily Sequential Organ Failure Assessment score and creatinine. Independent variables predicting ICU mortality were Simplified Acute Physiology Score II, mean Sequential Organ Failure Assessment score and SDMA. Conclusions: Dimethylarginines are not only markers of body catabolism may have a high metabolic activity, tightly related to the risk of adverse outcome of sepsis syndrome

OPEN-CHAIN PEPTIDES OBTAINED BY ACIDIC HYDROLYTIC CLEAVAGE OF CYCLOSPORINE-A

Hydrolysis of cyclosporin A (CsA) was studied in order to clarify the still undefined point of attack of the acidic degradation. Among ether extractable and water-soluble products formed from CsA in HCl, two open-chain peptides were isolated by high-performance liquid chromatography which were identified as the deca- and nonapeptides deriving from CsA through the hydrolytic cleavage of amino acid residue 11 and both residues 11 and 10, respectively. Identification was carried out by fast atom bombardment tandem mass spectrometry

Optical properties of aerosol particles over the Amazon rain forest: From background to biomass burning conditions

Atmospheric aerosols over the Amazon rainforest are strongly influenced by biomass burning activities in the southern regions of the Amazon Basin between July and October. This implies a complete change of the physical and chemical aerosol properties from the wet season, which is dominated by Primary Biological Aerosol Particles (PBAP) and biogenic secondary organic aerosols. Biomass burning emissions are highly loaded with light-absorbing aerosols, like black and brown carbon (BC and BrC, respectively). The latter one consists of a fraction of organic carbon that is able to absorb visible radiation (Andreae and Gelencs\ue9r, 2006). BrC is a strong absorber at near-UV to UV wavelengths. Therefore, light absorption by this component is wavelength dependent. This wavelength dependency, expressed as the absorption \uc5ngstr\uf6m exponent (AAE), has been used as a parameter to estimate the influence of biomass burning aerosols to total aerosol light absorption. However, the biogenic BrC contribution remains to be studied and could be significant under pristine conditions. The measurements presented here were carried out at the Amazon Tall Tower Observatory (ATTO), located 150 km NE of the city of Manaus, in the Uatum\ue3 Sustainable Development Reserve in Amazonas State, Brazil. The aerosol inlet (60 m high, 2.5 cm diameter) is installed on an 81-m triangular mast. The measurement period, from June to September 2014, includes the wetto- dry transition season (June-July) and part of the dry season (August and beginning of September). The optical properties were measured online by different instruments: 3-wavelengths nephelometer, Multi-Angle Absorption Photometer (MAAP), Single Particle Soot Photometer (SP2) and a 7-wavelength Aethalometer. Additionally, MAAP filter samples were analyzed by the Multi-Wavelength Absorbance Analyzer (MWAA) (Massab\uf2 et al, 2013), as well as levoglucosan analysis was carried out for filters collected between 18-22 August 2014. The average light absorption coefficient at 637 nm was 1.0 \ub1 0.6 Mm-1 and 5.5 \ub1 3.9 Mm-1, during the wet-to-dry transition and the dry season, respectively. Here we concentrate on measurements during 18-22 August 2014 (Figure 1) when a high absorption coefficient was measured at 637 nm, averaging 10 \ub1 3 Mm-1. The AAE calculated from MWAA measurements increased from less than 1.0 to values higher than 1.4, indicating the presence of BrC aerosol particles. This period is characterized by a long-range transport of biomass burning aerosol (confirmed by backward trajectory analysis). Levoglucosan analysis reveals significantly increased concentration but is still relatively low compared to measurements close to the source (Graham et al, 2002). Nevertheless, AAE and levoglucosan concentration show a significant correlation (r\ub2 &gt; 0.9)

Characterization of collagenase blend enzymes for human islet transplantation

BACKGROUND: Efficient islet isolation represents a necessary requirement for successful islet transplantation as a treatment for type 1 diabetes. The choice of collagenase for pancreas digestion is critical for the isolation outcome, and Liberase is the most widely used enzyme, although large intra-batched variability in activity and efficiency has been observed. METHODS: The aim of this study was to characterize Liberase components and their relative role in pancreas digestion. Liberase batches were characterized by microelectrophoresis. RESULTS: By means of microelectrophoresis, we identified three main proteins each with different prevalences between batches. Two proteins were found to correspond to class I (CI) and one to class II (CII) collagenase. In a series of 163 islet isolations, we observed that the CII correlated with islet yield (P50 percentile, 15 of 36 preparations were transplanted, with 27 of 127 transplanted in the other cases (P=0.013). CONCLUSION: These results represent an important step toward the characterization of enzymes, with the final aim of identifying key components for a standardized produc

Asymmetric dimethylarginine (ADMA), symmetric dimethylarginine (SDMA) and L-arginine in patients with arteriogenic and non-arteriogenic erectile dysfunction

The plasma concentration of asymmetrical dimethylarginine (ADMA), an inhibitor of nitric oxide synthase, has been linked to endothelial dysfunction. We investigated the relation between ADMA, symmetric dimethylarginine (SDMA) and L-arginine concentrations and erectile dysfunction. We compared plasma levels of ADMA, SDMA and L-arginine in 61 men in good health with erectile dysfunction of arteriogenic and non-arteriogenic origin. Diagnosis of erectile dysfunction was based on the International Index of Erectile Function Score and its aetiology was classified with penile echo-colour-Doppler in basal condition and after intracavernous injection of prostaglandin E1. The ADMA and SDMA concentrations were significantly higher in men with arteriogenic erectile dysfunction compared with those with erectile dysfunction of non-arteriogenic origin (p 0.05) nor between each of the two erectile dysfunction subgroups and controls (p > 0.05). The L-arginine/ADMA and the L-arginine/SDMA ratios in arteriogenic erectile dysfunction subgroups were significantly lower than both in controls (p 0.05). We conclude that ADMA and SDMA concentrations are significantly higher and L-arginine/ADMA ratio lower in patients who have arteriogenic erectile dysfunction compared with both patients with non-arteriogenic erectile dysfunction and controls. The negative correlation between ADMA and severity of erectile dysfunction is present only in patients with arteriogenic erectile dysfunction. This study supports the importance to always distinguish arteriogenic from non-arteriogenic erectile dysfunction patients to study the complicate erectogenic mechanisms that lead to erectile dysfunction and also to provide potential therapeutic agents for patients with arteriogenic erectile dysfunction

Tight glycemic control does not affect asymmetric-dimethylarginine in septic patients

OBJECTIVE: We investigated whether preventing hyperglycemia in septic patients affected the plasma concentration of asymmetric-dimethylarginine and if this was associated with clinical benefit. DESIGN: A prospective, multicenter, randomized, controlled, clinical study. SETTING: Intensive care units (ICU) in three university hospitals. PATIENTS: A total of 72 patients admitted for severe sepsis or septic shock, who stayed at least 3 days in the ICU. At admission the patients were assigned to receive either tight or conventional glycemic control. INTERVENTIONS: Determination of circulating levels of asymmetric-dimethylarginine, arginine, interleukin-6, C-reactive-protein and tumor-necrosis-factor-alpha. MEASUREMENTS AND RESULTS: Blood was sampled at admission (no differences between groups), and on the 3rd, 6th, 9th, and 12th (T12) days. Sequential organ failure assessment was scored at each sampling time. All the data were analyzed on an intention-to-treat basis. The control and treatment groups received the same energy intake, glycemia (110.4 +/- 17.3 vs. 163.0 +/- 28.9 mg/dL, P < 0.001) and insulin (P = 0.02) supply differed. No differences were found in high plasma levels of asymmetric-dimethylarginine (P = 0.812) at any time during the ICU stay. The clinical course, as indicated by markers of inflammation, average and maximum organ failure score, ICU stay and ICU and 90-day mortality, was the same. CONCLUSIONS: Intensive insulin treatment, while achieving glucose control, did not reduce asymmetric-dimethylarginine in high-risk septic patients fed with no more than 25 kcal/kg per day to limit ventilatory demand and to simplify glucose control. DESCRIPTOR: 45 (SIRS/sepsis: clinical studies)

EFFECTS OF AN ACUTE INCREASE IN PLASMA TRIGLYCERIDE LEVELS ON GLUCOSE-METABOLISM IN MAN

The aim of the study was to evaluate the effects of an acute increase in triglyceride levels induced by Intralipid (Kabivitrum, Stockholm, Sweden) infusion on forearm glucose uptake, glucose oxidative metabolism, and hepatic glucose production independent of circulating free fatty acid (FFA) levels in man. Six normal subjects underwent three different tests in random order. Each test consisted of a control period of 120 minutes followed by a euglycemic, hyperinsulinemic clamp lasting 120 minutes. In test 1, a high-dose intravenous Intralipid infusion was performed to increase triglyceride and FFA levels. In test 2, heparin (30 U/min) plus low-dose Intralipid infusions were performed to maintain triglyceride at normal levels and increase only FFA levels. Test 3 was performed as a control study. During the 120-minute control period, forearm glucose uptake and hepatic glucose production were not affected by increasing only FFA levels (test 2) or FFA and triglyceride levels (test 1) as compared with the control study. On the contrary, glucose oxidation was significantly decreased as compared with the control study during tests 1 and 2, without a further significant decrease during simultaneously increased FFA and triglyceride levels. Concomitantly, lipid oxidation was similar in tests 1 and 2, at values significantly greater than in test 3. During the euglycemic clamp, forearm glucose uptake and glucose oxidation were significantly lower during tests 1 and 2 than test 3. At variance with the control period, the increase of triglyceride levels during test 1 caused a significant 30% to 40% decrease of both parameters as compared with test 2. Opposite results were found for lipid oxidation, which remained unchanged during test 1 as compared with the control period but significantly decreased during tests 2 and 3. Hepatic glucose production was less inhibited during test 1 than during tests 2 and 3, and less so during test 2 than test 3. In conclusion, at least under these particular conditions, acute hypertriglyceridemia induced by Intralipid infusion seems to decrease forearm glucose uptake, glucose oxidation, and insulin-induced suppressibility of hepatic glucose production. Taking our results together, it seems that the triglyceride effect on carbohydrate metabolism occurs via triglyceride hydrolysis using the intracellular pathways of FFA without interference with the circulating FFA pool

Normohomocysteinaemia and vitamin-treated hyperhomocysteinaemia are associated with similiar risks of cardiovascular events in patients with premature peripheral arterial occlusive disease. A prospective cohort study

Objectives. Mild hyperhomocysteinaemia (HHC), fasting or after methionine loading, is associated with an increased risk and severity of atherosclerotic vascular disease. Post-methionine and fasting HHC are responsive to treatment with vitamin