Palmitoylethanolamide is a disease-modifying agent in peripheral neuropathy : pain relief and neuroprotection share a PPAR-alpha-mediated mechanism

Peer reviewedPublisher PD

(+/-)-Gelliusines A and B, two diastereomeric brominated tris-indole alkaloids from a deep water New Caledonian marine sponge (Gellius or Orina sp.)

Two new diastereomeric brominated tris-indole alkaloids occurring as enantiomeric pairs, (±)-gelliusine A (I) and its isomer (±)-gelliusine B, have been isolated from a deep water New Caledonian sponge (Gellius or Orina sp.), whose crude ext. exhibited cytotoxicity against KB cells. Their structures were elucidated by spectroscopic methods including one- and two-dimensional NMR spectroscopy. The major compd., I, which showed very weak cytotoxicity, proved to be active at the serotonin receptor

Assessment of neuroactive steroids in cerebrospinal fluid comparing acute relapse and stable disease in relapsing-remitting multiple sclerosis

Previous studies have reported an involvement of neuroactive steroids as neuroprotective and anti-inflammatory agents in neurological disorders such as multiple sclerosis (MS); an analysis of their profile during a specific clinical phase of MS is largely unknown. The pregnenolone (PREG), dehydroepiandrosterone (DHEA), and allopregnanolone (ALLO) profile was evaluated in cerebrospinal fluid (CSF) in relapsing-remitting multiple sclerosis (RR-MS) patients as well as those in patients affected by non-inflammatory neurological (control group I) and without neurological disorders (control group II). An increase of PREG and DHEA values was shown in CSF of male and female RR-MS patients compared to those observed in both control groups. The ALLO values were significantly lower in female RR-MS patients than those found in male RR-MS patients and in female without neurological disorder. During the clinical relapse, we observed female RR-MS patients showing significantly increased PREG values compared to female RR-MS patients in stable phase, while their ALLO values showed a significant decrease compared to male RR-MS patients of the same group. Male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Similary, male RR-MS patients with gadolinium-enhanced lesions showed PREG and DHEA values higher than male without gadolinium-enhanced lesions. Female RR-MS patients with gadolinium-enhanced lesions showed DHEA values higher than those found in female RR-MS patients with gadolinium-enhanced lesions. Male and female RR-MS patients with gadolinium-enhanced lesions showed ALLO values higher than those found in respective gender groups without gadolinium-enhanced lesions. ALLO values were lower in male than in female RR-MS patients without gadolinium-enhanced lesions. Considering the pharmacological properties of neuroactive steroids and the observation that neurological disorders influence their concentrations, these endogenous compounds may have an important role as prognostic factors of the disease and used as markers of MS activity such as relapses

Ketogal: A Derivative Ketorolac Molecule with Minor Ulcerogenic and Renal Toxicity

Ketorolac is a powerful non-steroidal anti-inflammatory drug (NSAID), with a great analgesic activity, present on the Italian market since 1991. Despite the excellent therapeutic activity, the chronic use of ketorolac has long been limited owing to the high incidence of gastrointestinal and kidney side events. In our previous study, we demonstrated that ketorolac–galactose conjugate (ketogal), synthesized and tested in a single-dose study, was able to reduce ulcerogenicity, while preserving the high pharmacological efficacy of its parent drug. In this paper, in order to verify the suitability of this compound, for repeated administration, ex vivo experiments on naïve mice were performed. Mice were treated for 5 or 7 days with the highest doses of two drugs (ketorolac 10 mg/kg and ketogal 16.3 mg/kg), and the expression of both gastric COX-1 and PGsyn was evaluated. Results showed that oral ketorolac treatment significantly reduced both enzymes; surprisingly, oral treatment with ketogal did not produce significant variation in the expression of the two constitutive enzymes. Moreover, histological experiments on stomach and kidneys clearly indicated that repeated administration of ketogal induced lower toxicity than ketorolac. At same time, in vivo results clearly showed that both ketorolac and ketogal had a similar therapeutic activity in a model of inflammation and in pain perception. These effects were accompanied by the reduction of enzyme expression such as COX-2 and iNOS, and by the modulation of levels of nuclear NF-kB and cytosolic IkB-a in the inflamed paws. These very encouraging results demonstrate for the first time that ketogal could represent a valid and novel therapeutic alternative to the ketorolac and might pave the way for clinical studies

Accuracy of complex internal channels produced by laser powder bed fusion process

Additive manufacturing (AM) technology has great potential in manufacturing complex internal channels for several applications such as satellite-communication microwave systems. These systems can have complex shapes and make traditional finishing processes a challenge for additive parts. Therefore, it is desirable that the internal surfaces are as close as possible to the tolerance of the field of application. In this study, a complex component, a unique waveguide device with bending, twisting and filtering functionalities, has been designed and manufactured in AlSi10Mg alloy through laser powder bed fusion (L-PBF) process. Three different prototypes with three different curvature (R of 50 mm, 40 mm and 30 mm), operating in Ku/K band, have been manufactured and tested showing a very good agreement with the desired performances. Using 3D scan data, the internal deviations from the CAD model have been evaluated showing an average deviation of the internal areas of about 0.08 mm, 0.046 mm and 0.023 mm from the CAD model for the R of 50 mm, 40 mm and 30 mm respectively The surface roughness measured in the internal channel is about Ra (arithmetic average roughness) of 8 μm ± 1.3 μm and Rz (average maximum height of the roughness profile) of 62.3 μm ± 0.34 μm

Synthesis of Oleoylethanolamide Using Lipase

An effective process for the enzymatic synthesis of oleoylethanolamide is described in this study. The process included purification of a commercial oleic acid product and then optimization of the reaction between the purified oleic acid and ethanolamine in the presence of hexane and a lipase. Under the optimal amidation reaction conditions identified, oleoylethanolamide was obtained with 96.6% purity. The synthesis was also conducted on a large scale (50 mmol of each of the reactants), and oleoylethanolamide purity and yield after crystallization purification were 96.1 and 73.5%, respectively. Compared to the previous studies, the current method of preparing high-purity oleoylethanolamide is more effective and economically feasible. The scalability and ease for such synthesis make it possible to study the biological and nutritional functions of the cannabinoid-like oleoylethanolamide in animal or human subjects

Experimental research activity on additive manufacturing of microwave passive waveguide components

All metal passive waveguide components are key building-blocks of several RF systems used for telecommunications, navigation, imaging, radio-astronomy, and cosmology. The accurate manufacture of these devices in Additive Manufacturing (AM) technologies can open the way to a high integration level of microwave functionalities with a significant cost and mass reduction. In the paper, after an introduction on the most common AM technologies with particular detail on selective laser melting (SLM) and stereo-lithography apparatus (SLA) processes, the results on the on-going research activity are discussed. Measured performances are reported for AM prototypes of Ku/K/Ka-band rectangular and circular waveguide lines, microwave filters and a smooth wall horn

Additive Manufacturing Technology for High Performances Feed Horn

In this work the design and manufacturing through selective laser melting technology of single-band dual circular feed-system operating in Ka-band is reported. In the feed design an AM oriented architecture has been employed. The measured performances confirms the good manufacturing of the system that satisfies very stringent requirements in terms of polarization purity

Effects of the solution and first aging treatment applied to as-built and post-HIP CM247 produced via Laser Powder Bed Fusion (LPBF)

In this work CM247LC, a low weldable Ni-Based alloy, was produced using selective laser melting (SLM). Despite the initial process parameter optimization, the low defect volume fraction was still uncompliant with manufacturing standards. This condition is principally caused by the high γ’ volume fraction which strongly affects the alloy weldability. Nonetheless, a crack free condition was eventually achieved applying a γ’-sub-solvus Hot Isostatic Pressing Cycle (HIP) which lowered the defects fraction down to 0.04%. The HIP cycle also demonstrated to play an important role in the stabilization of the microstructure, considerably limiting the carbides coarsening during the following heat treatment. Apart from the effectiveness of the healing process brought by HIP, the material microstructure still needs an optimization process which will be described along this paper. In fact, the Initial microstructure obtained after the printing process (the as-built condition) as well as the one obtained after HIP (post-HIP) won’t meet the desired requirements. Namely, the dendritic and γ’ free microstructure of the asbuilt material or the one with coarse and disordered particles obtained right after HIP, still need a tailored homogenization process. This paper will show how the combined effect of the solution and first aging treatment will profoundly alter the γ’ precipitation. More specifically, here, a new heat treatment recipe was developed to promote the precipitation of ordered cuboidal primary γ’ so as to improve creep and high temperature fatigue resistance. Moreover, the use of a γ’ super-solvus temperature allowed to achieve a γ’ volume fraction as high as 73% reducing its average size to 520 nm. At the same time, such heat treatment caused a profound alteration of the crystalline structures of the material promoting a general grain coarsening and the formation of equiaxial grain