An experimental pilot study of tacalcitol activities during modulation of parakeratotic skin features

Establishing guidelines and experimental models preclinical and clinical evaluations of new agents for treatment, and/or prevention of human diseases has become a task of crucial importance. Psoriasis is such one disease holding great interest for dermatology owing to its high rate of incidence and complexity of treatment. However the absence of psoriatic lesions in animals and the inability to induce them, calls for experimental techniques both in vitro and in vivo. The purpose of this study was to evaluate experimentally the effects of tacalcitol on cell proliferation and differentiation process. Thereafter a human pilot study on psoriatic patients has been developed.     

Cell-protection mechanism through autophagy in HGFs/<Emphasis Type="Italic">S. mitis</Emphasis> co-culture treated with Chitlac-nAg

Silver-based products have been proven to be effective in retarding and preventing bacterial growth since ancient times. In the field of restorative dentistry, the use of silver ions/nanoparticles has been explored to counteract bacterial infections, as silver can destroy bacterial cell walls by reacting with membrane proteins. However, it is also cytotoxic towards eukaryotic cells, which are capable of internalizing nanoparticles. In this work, we investigated the biological effects of Chitlac-nAg, a colloidal system based on a modified chitosan (Chitlac), administered for 24–48?h to a co-culture of primary human gingival fibroblasts and Streptococcus mitis in the presence of saliva, developed to mimic the microenvironment of the oral cavity. We sought to determine its efficiency to combat oral hygiene-related diseases without affecting eukaryotic cells. Cytotoxicity, reactive oxygen species production, apoptosis induction, nanoparticles uptake, and lysosome and autophagosome metabolism were evaluated. In vitro results show that Chitlac-nAg does not exert cytotoxic effects on human gingival fibroblasts, which seem to survive through a homoeostasis mechanism involving autophagy. That suggests that the novel biomaterial Chitlac-nAg could be a promising tool in the field of dentistry.     

Critical Role for the Protons in FRTL-5 Thyroid Cells: Nuclear Sphingomyelinase Induced-Damage

Proliferating thyroid cells are more sensitive to UV-C radiations than quiescent cells. The effect is mediated by nuclear phosphatidylcholine and sphingomyelin metabolism. It was demonstrated that proton beams arrest cell growth and stimulate apoptosis but until now there have been no indications in the literature about their possible mechanism of action. Here we studied the effect of protons on FRTL-5 cells in culture. We showed that proton beams stimulate slightly nuclear neutral sphingomyelinase activity and inhibit nuclear sphingomyelin-synthase activity in quiescent cells whereas stimulate strongly nuclear neutral sphingomyelinase activity and do not change nuclear sphingomyelin-synthase activity in proliferating cells. The study of neutral sphingomyelinase/sphingomyelin-synthase ratio, a marker of functional state of the cells, indicated that proton beams induce FRTL-5 cells in a proapoptotic state if the cells are quiescent and in an initial apoptotic state if the cells are proliferating. The changes of cell life are accompanied by a decrease of nuclear sphingomyelin and increase of bax protein.     

Vitamin C Enhances Vitamin E Status and Reduces Oxidative Stress Indicators in Sea Bass Larvae Fed High DHA Microdiets

Docosahexaenoic acid (DHA) is an essential fatty acid necessary for many biochemical, cellular and physiological functions in fish. However, high dietary levels of DHA increase free radical injury in sea bass (Dicentrarchus labrax) larvae muscle, even when vitamin E (α-tocopherol, α-TOH) is increased. Therefore, the inclusion of other nutrients with complementary antioxidant functions, such as vitamin C (ascorbic acid, vitC), could further contribute to prevent these lesions. The objective of the present study was to determine the effect of vitC inclusion (3,600?mg/kg) in high DHA (5?% DW) and α-TOH (3,000?mg/kg) microdiets (diets 5/3,000 and 5/3,000?+?vitC) in comparison to a control diet (1?% DHA DW and 1,500?mg/kg of α-TOH; diet 1/1,500) on sea bass larvae growth, survival, whole body biochemical composition and thiobarbituric acid reactive substances (TBARS) content, muscle morphology, skeletal deformities and antioxidant enzymes, insulin-like growth factors (IGFs) and myosin expression (MyHC). Larvae fed diet 1/1,500 showed the best performance in terms of total length, incidence of muscular lesions and ossification degree. IGFs gene expression was elevated in 5/3,000 diet larvae, suggesting an increased muscle mitogenesis that was confirmed by the increase in the mRNA copies of MyHC. vitC effectively controlled oxidative damages in muscle, increased α-TOH larval contents and reduced TBARS content and the occurrence of skull deformities. The results of the present study showed the antioxidant synergism between vitamins E and C when high contents of DHA are included in sea bass larvae diets.     

The d-index: Discovering dependences among scientific collaborators from their bibliographic data records

The evaluation of the work of a researcher and its impact on the research community has been deeply studied in literature through the definition of several measures, first among all the h-index and its variations. Although these measures represent valuable tools for analyzing researchers?? outputs, they usually assume the co-authorship to be a proportional collaboration between the parts, missing out their relationships and the relative scientific influences. In this work, we propose the d-index, a novel measure that estimates the dependence degree between authors on their research environment along their entire scientific publication history. We also present a web application that implements these ideas and provides a number of visualization tools for analyzing and comparing scientific dependences among all the scientists in the DBLP bibliographic database. Finally, relying on this web environment, we present case and user studies that highlight both the validity and the reliability of the proposed evaluation measure.     

Method development for the quantitative determination of lactulose in heat-treated milks by HPAEC with pulsed amperometric detection

A robust, rapid, and sensitive high-performance anion-exchange chromatographic method for the separation and quantitative determination of lactulose in heated milks, along with other common milk carbohydrates, has been developed. Complete separation of galactose, glucose, N-acetylgalactosamine, lactose, lactulose, and epilactose was isocratically accomplished in about 22 min by an anion-exchange column eluted with 10 mM NaOH spiked with 2 mM Ba(OAc)2. The within-day repeatability was lower than 2.1% for 10 repetitive injections. Under optimized conditions, there was no need either of post-column addition of strong bases to the eluent for enhancing detection sensitivity or, even more important, for column regeneration between chromatographic runs. Upon 100-fold sample dilution, the amperometric response of lactulose in milk samples was found to be linear up to 100 microM (r = 0.99935) with a limit of detection equal to 1.2 microM (S/N = 3). The lactulose content in ultrahigh-temperature (UHT) and sterilized milks was evaluated by a calibration graph using 2-deoxyglucose as the internal standard, making the proposed method very useful in discriminating among heat-treated milks. Whereas the mean value of lactulose in skimmed, partially skimmed, and whole UHT milks ranged from 10 to 90 mg/100 mL, lactulose content in bottle-sterilized whole milk (two samples) was higher than 140 mg/100 mL. The presence of epilactose, which is another isomer of lactose, was also ascertained in sterilized milk.     

Background, present state and future prospects of geothermal development

After a brief review of the nature, origin and occurrence of geothermal energy, the various conceptual models of geothermal systems are described.Subsequently the different utilizations of terrestrial heat (direct, indirect and combined) are described and the related production technologies are briefly illustrated.Following a historical overview of the development of geothermal energy, the current situation is presented (4719 MW electric and 12,000 MW thermal) and a projection for the end of the century is made (20,000–40,000 MWe and 19,000–33,000 MWt).A breakdown of geothermal projects and a block diagram of the costs and various activities is then presented and an average expenditure value is given.Finally, the role of geothermal energy in the overall energy context is discussed, as well as the main problems, both technical and non-technical, that will have to be faced in the future.     

Determination of methotrexate in untreated body fluids by micellar liquid chromatography

A fast and sensitive method for determination of the antineoplastic drug methotrexate in untreated serum and urine is described. Reversed-phase liquid chromatography with sodium dodecyl sulfate (SDS) micellar mobile phase has been used with direct sample injection. Changes in mobile phase variables such as SDS concentration and/or pH profoundly affected drug retention. Recovery was quantitative and the detection limit (90 nM for a 20 microL sample size) was below the range normally monitored. Multichannel UV detection provided strong evidence regarding peak purity and peak identity.     

Long-term and low-dose treatment with cabergoline induces macroprolactinoma shrinkage

Cabergoline (CAB), a long-lasting dopamine-agonist, specific for the D2 receptor, is effective in normalizing serum PRL levels in most patients with microprolactinoma or idiopathic hyperprolactinemia. Because few data are presently available on the effects of CAB treatment in macroprolactinomas, the aim of this open-label study was to investigate whether this drug was effective in producing tumor shrinkage, as well as in normalizing PRL levels. Twenty-three patients with macroprolactinoma entered this study 15 patients had had no treatment, whereas the remaining 8 patients had been previously treated with bromocriptine, which was with-drawn because of intolerance. Three of 23 patients had undergone unsuccessful surgery. Pretreatment serum PRL levels ranged from 100-3860 micrograms/L. CAB was administered at a dose of 0.5-3 mg once or twice a week for 12-24 months. Magnetic resonance imaging (MRI) scans were performed before and 3, 6, 12, and 24 months after the beginning of treatment, to evaluate tumor shrinkage, defined as a decrease of at least 80% of baseline tumor volume. After 3-6 months of treatment with a low dose (0.5-1 mg/week), serum PRL levels normalized in 18 patients. In the remaining 5 patients, whose serum PRL levels were not normalized, the dose was increased to 2-3 mg/week. This schedule caused the normalization of PRL levels in 1 patient, whereas in the remaining 4 patients, PRL levels were reduced to 30-82 micrograms/L. A tumor volume reduction greater than 80% at MRI occurred in 14 of 23 patients (61%) after CAB treatment (from 2609.4 +/- 534.7 to 530.1 +/- 141.3 mm3 at the 12-24th month follow-up, P < 0.001). A volume reduction of 41.8 +/- 3.4% was already evident after 3 months (1436 +/- 285.9 mm3; P < 0.001). The complete disappearance of the tumor mass at MRI occurred after 6 months of treatment with CAB in 1 patient, and in 5 patients after 1 yr of treatment. An improvement of visual field defects was obtained in 9 of the 10 patients presenting visual impairment before CAB treatment. The drug was tolerated well by all patients. Only 1 patient experienced mild nausea, which disappeared spontaneously after the 2nd day of treatment. Long-term, a low dose of the D2 receptor agonist CAB significantly reduced tumor volume and normalized serum PRL levels in a great majority of patients bearing macroprolactinoma. This treatment met with excellent patient compliance. This study suggests that CAB can be used as a first choice drug treatment in macroprolactinomas, as already shown for microprolactinomas and idiopathic hyperprolactinemia.     

Calcitonin and beta-endorphin secretion

Calcitonin is a peptide hormone secreted by the C-cells of the thyroid gland. This hormone mainly acts in preventing bone resorption. Furthermore, calcitonin is involved in other biological actions, and in particular it is able to relieve pain independently of its peripheral effects on bone. Here, we examine the possible mechanisms of calcitonin-induced analgesia, with particular regard to the opioid system involvement. Several studies in animals and in humans demonstrate that calcitonin increases plasma beta-endorphin levels, acting at the hypothalamic and/or at the pituitary level, either directly or indirectly, through monoaminergic neurotransmitters. However, this calcitonin-induced beta-endorphin release has not always been observed. These different results are discussed, and a possible implication of sex and/or calcitonin dose employed has been examined. We conclude that the analgesic effects of calcitonin are multifactorial, and beta-endorphin plays its own specific role.