A new co-micronized composite containing palmitoylethanolamide and polydatin shows superior oral efficacy compared to their association in a rat paw model of carrageenan-induced inflammation.

Palmitoylethanolamide (PEA), a special food for medical purposes, has anti-inflammatory and neuroprotective effects. Nevertheless, PEA lacks direct ability to prevent free radical formation. Polydatin (PLD), a natural precursor of resveratrol, has antioxidant activity. The combination of PEA and PLD could have beneficial effects on oxidative stress induced by inflammatory processes. In the present study, we compared the effects of micronized PEA (PEA-m) and PLD association (PEA-m+PLD) with a new co-micronized composite containing PEA and PLD (m(PEA/PLD)) in the rat paw model of carrageenan (CAR)-induced acute inflammation. Intraplantar injection of CAR led to a time-dependent development of peripheral inflammation, in terms of paw edema, cytokine release in paw exudates, nitrotyrosine formation, inducible nitric oxide synthase and cyclooxygenase-2 expression. m(PEA/PLD) reduced all measured parameters. Thermal hyperalgesia and mechanical allodynia were also markedly reduced. At the spinal cord level, manganese superoxide dismutase (MnSOD) was found to be nitrated and subsequently deactivated. Further, m(PEA/PLD) treatment increased spinal MnSOD expression, prevented IkB-α degradation and nuclear factor-κB translocation, suggesting a possible role on central sensitization. m(PEA/PLD) showed more robust anti-inflammatory and anti-hyperalgesic effects compared to the simple association of PEA-m and PLD. This composite formulation approach opens a new therapeutic strategy for the development of novel non-narcotic anti-hyperalgesic agents.

A novel protective formulation of Palmitoylethanolamide in experimental model of contrast agent induced nephropathy.

Contrast-induced nephropathy (CIN) is a complication in patients after administration of iodinated contrast media. Several risk factors contribute to the development and progression of CIN, including hypertension, diabetes, and dyslipidemia. Animal models of CIN by surgical intervention to reproduce its clinical and pathology has been developed, and thus, therapeutic methods tested. Palmitoylethanolamide (PEA) is a member of the fatty acid ethanolamine family with analgesic and anti-inflammatory effects. In this study, we analyzed streptozotocin-induced diabetes model and in an another set of experiment a surgical remotion of the kidney with the aim of evaluating effect of ultramicronized Palmitoylethanolamide (PEA-um(®)) on contrast induced renal disfunction and glomerular morphology alteration. In a first step of our study, we demonstrated that PEA-um(®) significantly reduced CIN-mediated glomerular dysfunction, modulates Na(+) and K(+) levels in plasma and decreased urine and plasma NGAL levels and α-GST urine levels. Moreover, in a second set of experiment we investigated how PEA-um(®) reduced creatinine and BUN plasma levels after nephrectomy, ameliorate renal and medullary blood flow and re-established renal parenchymal after CIN induction as well as after nephrectomy. Take together our results demonstrated that PEA-um(®) are able to preventing CIN in diabetic rats and alteration of biochemical parameters after nephrectomy.

Straightforward relative quantitation and age-related human standards of N-acetylaspartate at the centrum semiovale level by CSI (1)H-MRS.

1H-MRS was aimed to monitor metabolite concentrations in homogeneous interaxial slices of cerebral matter at the centrum semiovale level in healthy volunteers. NAA (N-acetylaspartate + N-acetylglutamate), Cr (creatine + phosphocreatine), and Cho (choline + acetylcholine) were evaluated by resonance integrations. Using Cr as an internal standard, NAA/Cr ratio was considered as a relative measure of concentration. CSI sequence explored volunteer's interaxial slices of white and gray matter by means of 8 x 8 matrices of (1)H-NMR spectra. NAA/Cr integral ratios were averaged over the whole spectral matrix to obtain the Index of NAA at Centrum Semiovale (INACS) of each individual. Indexes of the sixty-eight healthy volunteers, divided into three groups by age, showed good intraindividual reproducibility, and were virtually unaffected by small shifts or bendings of the interaxial slice analyzed. The INACSs were used to estimate Age-Sectorial INACS Ranges (ASIR), the intervals that, on the basis of a normal statistical distribution, should comprise 95% of the age-matched healthy population. Individual INACSs, compared to accurately defined ASIRs taken as standards, could early detect subtle, diffuse neuronal or axonal damage within centrum semiovale interaxial slices. Periodic inspection of INACS could also allow monitoring of progressive neuronal or axonal degeneration.

Plasma serotonin levels in Italian Fresian dairy cows.

The aim of this work was to investigate the metabolism of plasma serotonin or 5-hydroxytryptamine (5-HT), an important neurotransmitter, in Fresian dairy cows, a breed of zootechnical interest, using high-performance liquid chromatography with electrochemical detection. The subjects under study were at the stage of early lactation (n = 10; mean body weight 375 +/- 50 kg; average age of 3 years; body condition score 2.5), bred in a farm at an altitude of 150 m a.s.l. To evaluate animal welfare on this farm, which is closely connected to an animal's physiological status, tryptophan and cortisol levels (measured by enzyme-linked immunosorbent assay), together with levels of certain blood components [total proteins (TP), albumin, creatinine, glucose (Glu), triglycerides, phospholipids, total cholesterol, and aspartate transaminase, measured by spectrophotometry] were analyzed. The results obtained are discussed in comparison with reference values, taking into account the environmental living conditions. Measured plasma serotonin concentrations, which were lower than values reported for Brown Swiss dairy cows of a comparable age and diet, appeared to be affected by breed, temperature, blood sampling season, and altitude. Additional differences between the levels of plasma tryptophan, the amino acid precursor of serotonin, of the two breeds were comparable. Negative correlations between plasma tryptophan and plasma cortisol levels (r = -0.83, P < 0.005), plasma serotonin and plasma TP levels (r = -0.72, P < 0.05), or Glu levels (r = -0.77, P < 0.05) highlight the existence of a stress condition, which is connected to an energetic deficit related to lactation.

Preliminary evaluation of sensititre system for identifying gram-negative bacilli.

The automated microdilution Sensititre System (Sensititre, LtD.) was evaluated for the identification of 120 clinically isolated fermenter and non-fermenter Gram negative bacilli and of 12 ATCC reference strains (American Type Culture Collection). Daily and overnight (5 and 18 hours) identifications were performed according to the manufacturer. In both cases, the results were compared with those obtained with the overnight API 20E (API System, La Balme les Grottes, Montalieu Vercieu) used as reference method. Concordance between the results obtained after 5 hrs of incubation and those obtained with API 20E was found in 65% of cases (acceptable identification criteria with probability over 80%). When results were determined after 18 hrs of incubation (identification criteria with probably over 80%) concordance was found in 82.5%. Reproducibility obtained by repeated (10 times) identification with four different strains was 100% both at 5 hrs and 18 hrs. Identification accuracy of the 12 ATCC strains was 8/12 (66.6%) after 5 hrs and 12/12 (100%) after 18 hrs.