Pharmacological and clinical overview of cloperastine in treatment of cough

Cough constitutes an impressive expression of the normal defense mechanisms of the respiratory system. Productive cough associated with catarrh is an important protective system for the lung because it favors the upward movement of secretions and foreign bodies to the larynx and mouth. Cough may also appear without bronchial secretions, as dry cough, which may be persistent when inflammatory disease is chronic or when, in the early stages of respiratory disease, bronchial secretions are not yet fluid. Sometimes bronchitis-induced cough does not significantly affect quality of life, whilst in other cases cough may become so intense as to impair daily activities severely, resulting in permanent disability. This type of cough is one of the most frequent reasons for seeking medical advice. The use of cough suppressants may be appropriate for reaching a precise diagnosis and when dry cough is persistent. Cloperastine has been investigated in various types of cough and, unlike codeine, has been shown to possess dual activity. It also acts as a mild bronchorelaxant and has antihistaminic activity, without acting on the central nervous system or the respiratory center. Here we review the preclinical and clinical evidence of the efficacy and tolerability of cloperastine

A novel system for measuring damaging impacts on table olives

The consumer today demands high quality products; fruit with defects or in poor condition generate dissatisfaction and a consequent reduction in consumption. In recent years, interesting systems have been used (i. e. "artificial fruit") in order to identify the cause of damage during mechanical harvesting and/or post-harvest operations. In this paper, the authors present a new system designed to measure the impacts received by table olives in the processing stages from harvesting to packaging. The device is an instrumented sphere designed and implemented by the Agricultural Mechanics Section of the Department of Agricultural and Forest Sciences, University of Palermo, Italy. It contains a triaxial Micro Electro-Mechanical Systems (MEMS) sensor capable of acquiring acceleration from a few mg to 400 g (where g is the gravitational acceleration). It has a microcontroller with software developed for the specific application, a 16 bit A / D converter that allows a resolution of a few mg, a mini-USB port for connection to a master, which is connected to the PC via a common USB port. The master communicates with the sphere to download the data and to adjust parameters such as the data acquisition frequency, which can reach up to 1 kHz (50 Hz, 100 Hz, 400 Hz and 1 kHz). Preliminary tests performed on the functionality of the acquisition system show that the information obtained by the instrumented sphere are useful for identifying the stresses the fruits are subjected to during harvesting and post-harvest

Selective transcription and cellular proliferation induced by PDGF require histone deacetylase activity

Histone deacetylases (HDACs) are key regulatory enzymes involved in the control of gene expression and their inhibition by specific drugs has been widely correlated to cell cycle arrest, terminal differentiation, and apoptosis. Here, we investigated whether HDAC activ- ity was required for PDGF-dependent signal transduction and cellular proliferation. Exposure of PDGF-stimulated NIH3T3 fibroblasts to the HDAC inhibitor trichostatin A (TSA) potently repressed the expression of a group of genes correlated to PDGF-dependent cel- lular growth and pro-survival activity. Moreover, we show that TSA interfered with STAT3-dependent transcriptional activity induced by PDGF. Still, neither phosphorylation nor nuclear translocation and DNA-binding in vitro and in vivo of STAT3 were affected by using TSA to interfere with PDGF stimulation. Finally, TSA treatment resulted in the suppression of PDGF-dependent cellular prolif- eration without affecting cellular survival of NIH3T3 cells. Our data indicate that inhibition of HDAC activity antagonizes the mitogenic effect of PDGF, suggesting that these drugs may specifically act on the expression of STAT-dependent, PDGF-responsive genes

Melanocortin peptides inhibit urate crystal-induced activation of phagocytic cells

Introduction The melanocortin peptides have marked antiinflammatory potential, primarily through inhibition of proinflammatory cytokine production and action on phagocytic cell functions. Gout is an acute form of arthritis caused by the deposition of urate crystals, in which phagocytic cells and cytokines play a major pathogenic role. We examined whether alpha-melanocyte-stimulating hormone (\u3b1-MSH) and its synthetic derivative (CKPV)2 influence urate crystal-induced monocyte (Mo) activation and neutrophil responses in vitro. Methods Purified Mos were stimulated with monosodium urate (MSU) crystals in the presence or absence of melanocortin peptides. The supernatants were tested for their ability to induce neutrophil activation in terms of chemotaxis, production of reactive oxygen intermediates (ROIs), and membrane expression of CD11b, Toll-like receptor-2 (TLR2) and TLR4. The proinflammatory cytokines interleukin (IL)-1\u3b2, IL-8, and tumor necrosis factor-alpha (TNF-\u3b1) and caspase-1 were determined in the cell-free supernatants. In parallel experiments, purified neutrophils were preincubated overnight with or without melanocortin peptides before the functional assays. Results The supernatants from MSU crystal-stimulated Mos exerted chemoattractant and priming activity on neutrophils, estimated as ROI production and CD11b membrane expression. The supernatants of Mos stimulated with MSU in the presence of melanocortin peptides had less chemoattractant activity for neutrophils and less ability to prime neutrophils for CD11b membrane expression and oxidative burst. MSU crystalstimulated Mos produced significant levels of IL-1\u3b2, IL-8, TNF-\u3b1, and caspase-1. The concentrations of proinflammatory cytokines, but not of caspase-1, were reduced in the supernatants from Mos stimulated by MSU crystals in the presence of melanocortin peptides. Overnight incubation of neutrophils with the peptides significantly inhibited their ability to migrate toward chemotactic supernatants and their capacity to be primed in terms of ROI production. Conclusions \u3b1-MSH and (CKPV)2 have a dual effect on MSU crystal-induced inflammation, inhibiting the Mos' ability to produce neutrophil chemoattractants and activating compounds and preventing the neutrophil responses to these proinflammatory substances. These findings reinforce previous observations on the potential role of \u3b1-MSH and related peptides as a new class of drugs for treatment of inflammatory arthritis

Il pericolo ancora sottovalutato delle interazioni tra farmaci. Un caso clinico esemplificativo

Treatment of hypercholesterolemia has been shown to reduce mortality in patients with coronary artery disease. Patients with severe lipid abnormalities may require high-dose statin therapy, at times used in combination with additional agents. The occurrence of rhabdomyolysis is one of the rare side-effects of the cholesterol-lowering agents. During the use of simvastatin, the risk of this side-effect might be increased when macrolides are used concomitantly. The interacting mechanism likely was inhibited cytochrome P450 (CYP) 3A4 metabolism and possibly P-glycoprotein transport of simvastatin as well. We present a patient who developed rhabdomyolysis during the concomitant use of simvastatin and erythromycin. Coprescribing of medications not compatible with statins occurs frequently: to prevent future events, it is crucial that clinicians recognize the interaction risk associated with coprescribing, to assure that the risk of untoward effects is mitigated

Anti-Invasive Activity of Bovine Lactoferrin against Listeria monocytogenes.

We have investigated the possible role of bovine lactoferrin in protecting the intestinal epithelium from bacterial infections, using as an in vitro model enterocyte-like cell lines HT-39 and Caco-2 infected with a food-borne pathogen, Listeria monocytogenes . When infection occurred in the presence of 1 mg/ml of bovine lactoferrin, in the form of apolactoferrin or iron- or manganese-saturated forms, the adhesion of bacteria to eukaryotk cells was unaffected, but the number of internalized bacteria was reduced by 42- to 125-fold. The possibility of a toxic effect of lactoferrin was excluded, because bovine lactoferrin was used at nonbactericidal and noncytotoxic concentrations

Antifungal and anti-biofilm activity of the first cryptic antimicrobial peptide from an archaeal protein against Candida spp. clinical isolates

Candida species cause cutaneous and systemic infections with a high mortality rate, especially in immunocompromised patients. The emergence of resistance to the most common antifungal drugs, also due to bioflm formation, requires the development of alternative antifungal agents. The antimicrobial peptide VLL-28, isolated from an archaeal transcription factor, shows comparable antifungal activity against 10 clinical isolates of Candida spp. Using a fuoresceinated derivative of this peptide, we found that VLL-28 binds to the surface of planktonic cells. This observation suggested that it could exert its antifungal activity by damaging the cell wall. In addition, analyses performed on bioflms via confocal microscopy revealed that VLL-28 is diferentially active on all the strains tested, with C. albicans and C. parapsilosis being the most sensitive ones. Notably, VLL-28 is the frst example of an archaeal antimicrobial peptide that is active towards Candida spp. Thus, this points to archaeal microorganisms as a possible reservoir of novel antifungal agent