Engineered mucoperiosteal scaffold for cleft palate regeneration towards the non-immunogenic transplantation.

Cleft lip and palate (CL/P) is the most prevalent craniofacial birth defect in humans. None of the surgical procedures currently used for CL/P repair lead to definitive correction of hard palate bone interruption. Advances in tissue engineering and regenerative medicine aim to develop new strategies to restore palatal bone interruption by using tissue or organ-decellularized bioscaffolds seeded with host cells. Aim of this study was to set up a new natural scaffold deriving from a decellularized porcine mucoperiosteum, engineered by an innovative micro-perforation procedure based on Quantum Molecular Resonance (QMR) and then subjected to in vitro recellularization with human bone marrow-derived mesenchymal stem cells (hBM-MSCs). Our results demonstrated the efficiency of decellularization treatment gaining a natural, non-immunogenic scaffold with preserved collagen microenvironment that displays a favorable support to hMSC engraftment, spreading and differentiation. Ultrastructural analysis showed that the micro-perforation procedure preserved the collagen mesh, increasing the osteoinductive potential for mesenchymal precursor cells. In conclusion, we developed a novel tissue engineering protocol to obtain a non-immunogenic mucoperiosteal scaffold suitable for allogenic transplantation and CL/P repair. The innovative micro-perforation procedure improving hMSC osteogenic differentiation potentially impacts for enhanced palatal bone regeneration leading to future clinical applications in humans.

[Stress in auto-transportation sector between prejudice and reality]. / Stress nel settore autotrasporti tra pregiudizio e realtà.

Every year in the EU about 800 drivers die in road accidents. In Italy the average is around 200 deaths per year. Based on this context the Occupational Medicine Department (OMD) of Bergamo Hospital has sponsored a new project dedicated to the healthcare and safety of all employees of road haulage in the province of Bergamo. Furthermore the collaboration between UMD and the Clinical Psychology Department of the hospital has allowed the fulfillment of another project aiming to evaluate the personality profile of around 80 drivers employed in the road haulage sector". The aims of the projects is to identify and to point out dangerous situations of significant psychological vulnerability; to know the current situation and to discriminate stress factors from protective ones; to make companies more aware of prevention activities; to inform the drivers about their companies' policy in order to grant safety in their job. The psychological tools used were: half open interview and Personality Inventory MMPI2. The population was selected randomly from volunteers. Now we know the results in 33 tested drivers. So far seven cases have been classified as psychological vulnerable and stress and protective factors have been identified. Results underline the relevance of an integrated approach able to take care of the employees and involving the companies in the prevention programs.

Determination of homovanillic acid (HVA) in human plasma by HPLC with coulometric detection and a new SPE procedure.

A sensitive high-performance liquid chromatographic method has been developed for the determination of homovanillic acid (HVA), the main metabolite of dopamine, in human plasma. Analyses were carried out on a reversed-phase column (C8, 250 mm x 4.6 mm i.d., 5 microm) using a mobile phase composed of 10% methanol and 90% aqueous citrate buffer, containing octanesulfonic acid and EDTA at pH 4.8. Coulometric detection was used, setting the guard cell at +0.100 V, the first analytical cell at -0.200 V and the second analytical cell at +0.500 V. A careful solid-phase extraction procedure, based on strong anion exchange (SAX) cartridges (100 mg, 1 mL), was implemented for the pre-treatment of plasma samples. Extraction yield was satisfactory, being the mean value 98.0%. The calibration curve was linear over the concentration range of 0.2-25.0 ng mL(-1) of homovanillic acid. The limit of quantitation (LOQ) was 0.2 ng mL(-1) and the limit of detection (LOD) was 0.1 ng mL(-1). The method was successfully applied to plasma samples from former alcohol, cocaine and heroin addicts. Results were satisfactory in terms of precision and accuracy. Hence, the method is suitable for the determination of homovanillic acid in human plasma.

HPLC analysis of the novel antipsychotic drug quetiapine in human plasma.

A precise and feasible high-performance liquid chromatographic (HPLC) method for the analysis of the novel antipsychotic drug quetiapine in plasma has been developed. The analysis was carried out on a C8 (150x4.6 mm i.d., 5 micrometer) reversed-phase column, using a mixture of acetonitrile, methanol and pH 1.9 phosphate buffer as the mobile phase; triprolidine was used as the internal standard. Careful pretreatment of the biological samples was implemented by means of solid-phase extraction (SPE). A good linearity was found in the 4-400 ng ml(-1) quetiapine plasma concentration range. The application to some plasma samples of patients treated with Seroquel(R) tablets gave satisfactory results. The accuracy was good (quetiapine mean recovery=92%), as well as the precision (mean RSD=3.3%). The method seems to be suitable for the clinical monitoring of patients treated with quetiapine.

Analysis of reboxetine, a novel antidepressant drug, in pharmaceutical tablets by capillary electrophoresis and derivative spectrophotometry.

The recent antidepressant drug reboxetine was quantified in pharmaceutical tablets by derivative spectrophotometry and capillary zone electrophoresis. The feasible sample pretreatment consists of a single extraction with a pH 2.5 phosphate buffer, centrifugation and dilution. For the spectrophotometric assay, the fourth derivative of the absorbance was used which gave satisfactory results in terms of accuracy (mean recovery 99.7%) and precision (mean RSD 3.4%). The electrophoretic experiments were carried out using the shortest effective length of the capillary (8.5 cm) in order to obtain a very rapid separation of reboxetine and dibenzepine used as the internal standard. Using a pH 2.5, 50 mM phosphate buffer as the background electrolyte, each analysis lasted less than 2.5 min. Accuracy (101.3%) and precision (1.5%) were very good.

Some new quinoline-based mono and dicarboxylic acids.

Some quinoline-based mono- and dicarboxylic acids structurally related to kynurenic acid have been synthesized and screened as antagonists of neurotransmission of NMDA, AMPA and KA excitatory amino acid receptors. Higher affinity for NMDA receptor was pointed out in the short series, but all the compounds, even those with key structural features of glutamic acid showed no significant activity.

Some new 1,2,3,4-tetrahydroquinoline derivatives.

Two 1,2,3,4-tetrahydoquinoline-based compounds were synthesized and evaluated for antinociceptive properties. Both compounds displayed no significant analgesic activity and at the higher dose showed no characterized CNS depressant activity.

Synthesis and antimicrobial activity of some N-monosubstituted 2-(2-aminothiazol-4-yl)-(Z)-2-methoxyiminoacetamides.

A short series of N-monosubstituted (aryl, aminoacyl, dipeptidyl)-2-(2-aminothiazol-4-yl)-(Z) -2-methoxyiminoacetamides was synthesized and tested for antimicrobial activity. A few members showed a somewhat interesting inhibitory action against Cryptococcus neoformans (MIC = 150 micrograms/ml).

Synthesis and antimycotic activity of some benzyloxyimino compounds.

Some benzyloxyimio compounds, related to oxiconazole and having a 1H-indole or 1H-benzimidazole moiety, have been synthesized and tested in vitro for their antimycotic activity against Candida tropicalis and C. albicans. The most active was showed to be 0-(2,4-dichlorobenzyl)-1-benzyl-5-nitro-1H-benzimidazole-2-carboxaldehyd e oxime (MIC: 25 micrograms/ml against both microorganisms). A structural feature important for the biological activity of the series appears to be presence of a benzimidazole nucleus substituted by an electron withdrawing group.

Synthesis and antimicrobial activity of some new benzodifurans and phenanthrolines.

A short series of di-functionalized benzodifurans and phenanthrolines were synthesized for in vitro antimicrobial activity. Dicarboxaldehydes, chiefly those with a phenanthroline supporting moiety, proved to be most effective, showing significant fungal growth inhibition.

[Hydrazines containing 1H-indene units]. / Idrazine contenenti unità 1H-indenica.

Some derivatives of N'-(5-nitro-2-furoyl)-N2-(3-chloro-1H-indenyl-2-methylene)hydrazine (I) were synthesized and screened for in vitro antimicrobial activity. None was more active than the parent compound and the greater hydrophilic character was associated with loss of inhibitory activity against gram-negative bacteria.

[Preparation of 1-(5'-nitrofurfuryl)-5-halouracils]. / Preparazione di 1-(5'-nitrofurfuril)-5-alogenouracili.

Some 1-(5'-nitrofurfuryl)-5-halouracils were synthetized and tested in vitro for antimicrobial activity. N.M.R. spectra of the compounds proved 1-substitution on uracil.

[Naphthofuran derivatives with potential beta-adrenolytic activity]. / Derivati naftofuranici a possibile azione beta-adrenolitica.

1-(Naphtho[1,2-b]furan-2-yl)-2-(isopropylamino)ethanol (II) and 1-(naphtho[2,3-b]furan-2-yl)-2-(isopropylamino)ethanol (III) show low beta-adrenergic blocking activity and unlike the naphtho [2,1-b]furan derivatives (1,2) do not appear to give rise to metabolites with high beta-adrenoceptor inhibitory properties. The inclusion of the --OCH2-- moiety in an aromatic nucleus larger than the benzofuran system (bufuralol, Ro 3-3528) caused loss of the biological activity.

[Antimicrobial activity of various hydrazones containing benzofuran and 1H-indene units]. / Attività antimicrobica di alcuni idrazoni contenenti unità benzofuranica e 1H-indenica.

A few hydrazones holding benzofuran and 1H-indene moieties were synthesized and screened for in vitro antimicrobial activity. The most active N'-(5-nitro-2-furoyl)-N2-(3-chloro-1H-indenyl-2-methylene)hydrazine (II c) showed higher activity than nitrofurantoin against some microorganisms, especially Pseudomonas aeruginosa.

[Preparation and analgesic activity of tetrahydroquinolines and tetrahydroisoquinolines]. / Preparazione ed attività analgesica di alcune tetraidrochinoline e tetraidroisochinoline.

A series of 1,2,3,4-tetrahydroquinolines and of 1,2,3,4-tetrahydroisoquinolines were synthesised and evaluated for analgesic activity by both hot-plate and acetic acid writhing methods in rats. Te most potent compound was 2-methyl-1,2,3,4-tetrahydro-5-quinolinol (IV i) which was shown to be 1/8 and 1/50 as active as morphine according to the employed assay. The analgesic activity was shown to be associated to a not selective action on the CNS.

[Research on substances with antiviral activity. XVIII. Bis-amidinohydrazones of N-heterocyclic aromatic dialdehydes]. / Richerche su sostanze ad attività antivirale. Nota XVIII - bis-amidinoidrazoni di dialdeidi aromatiche N-eterocicliche.

Some bis-amidinohydrazones of N-heterocyclic aromatic dialdehydes were synthesised and tested in vitro against the MP mutant of the herpes simplex virus type 1 [HSV - I (MP)]. Of the compounds tested, only those with and indole substrate showed some measure of biological activity.

[Studies of substances with antiviral activity. VI. Activity on Herpes simplex virus of bis-homoanalogs of nucleosides and of hydrazone derivatives of various aromatic substrates]. / Ricerche su sostanze ad attività antivirale. Nota VI - attività su virus dell'herpes simplex di bis-omoanaloghi di nucleosidi e di derivati idrazonici di alcuni substrati aromatici.

Derivatives of different chemical structures, namely hydrazones of aromatic compounds and bis-homoanalogues of pyrimidine and purine nucleosides, have been investigated for inhibiting activity on Herpes simplex virus infection of human HEp-2 cell cultures. Some thiosemicarbazones, nucleoside analogues and guanylhydrazones proved active [compounds (I), (II b), (II c), (III), (IV a), (IV b), (V a), (V b); Fig. 1]. An increase in the number of guanylhydrazone chains linked to a fluorene structure [from 1 to 3: compounds (II a), (II b) and (II c)] increased the "activity index" (i.e., toxic versus active concentrations: Table II). Further in vitro investigations have been carried out on bis-guanylhydrazone of 1-phenyl-2-chloro-3,7-diformylindole (I) and it was found that its activity is of the order of 1 microgram per ml (Fig. 3). The compound completely blocks low multiplicity infections while it only blocks cytopathogenicity, not viral replication, in high multiplicity infections.