Innovation and market structure in the dynamics of the pharmaceutical industry and biotechnology: towards a history-friendly model

This paper is a first attempt at modelling the long-term dynamicsof market structure and innovation in the pharmaceutical industryin a history-friendly way. The model examines the relationshipsbetween the nature of the search space, demand, the patternsof competition, and industry evolution in the age of randomscreening and in the age of molecular biology, and shows thatconcentration in the pharmaceutical industry is shaped by lackof cumulativeness in innovative activities and market fragmentation.The model conforms to our appreciative understanding and respondsto changes in parameters concerning demand, costs, economiesof scale, opportunity conditions and the relative advantagesof new biotechnology firms (NBFs) vis-à-vis incumbents.With the exception of cost increases, the model is quite robustto these changes in its essential features: it is quite difficultto raise substantially concentration and to have NBFs displacingincumbents.     

Volatile components of artemisia vallesiaca all. (Mountain wormwood)

Summary The essential oil obtained by steam distillation of the leaves and flowers ofArtemisia vallesiaca All., a plant widely employed in the liqueur making industry and of almost completely unknown chemical composition, after separation on a silica gel column, was investigated by means of GLC, IR and mass spectrometry. Camphene, 1,8-cineole, camphor and borneol accounted for 67–68% of the oil. Over one hundred minor compounds were found by capillary gas chromatography and 52 were identified (Table 1).

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Die flüchtigen Aromastoffe von Artemisia vallesiaca All. (Berg-Genippi)

Zusammenfassung Das ätherische Öl — erhalten durch Wasserdampfdistillation aus Blättern und Blüten derArtemisia vallesiaca All., einer Pflanze, die in der Wermut-und Likörproduktion viel verwendet wird, aber chemisch fast unbekannt ist — wurde nach Säulenchromatographie an Kieselgel analysiert mittels GLC, IR und GLC-MS. Camphen, 1,8-Cineol, Campher und Borneol bilden 67–68% des ätherischen Öl. Mehr als 100 weitere Bestandteile wurden durch GLC gefunden und 52 von diesen wurden identifiziert (Tabelle 1).

     

Salicylketoximes That Target Glucose Transporter 1 Restrict Energy Supply to Lung Cancer Cells

The glucose transporter GLUT1 is frequently overexpressed in most tumor tissues because rapidly proliferating cancer cells rely primarily on glycolysis, a low‐efficiency metabolic pathway that necessitates a very high rate of glucose consumption. Because blocking GLUT1 is a promising anticancer strategy, we developed a novel class of GLUT1 inhibitors based on the 4‐aryl‐substituted salicylketoxime scaffold. Some of these compounds are efficient inhibitors of glucose uptake in lung cancer cells and have a notable antiproliferative effect. In contrast to their 5‐aryl‐substituted regioisomers, the newly synthesized compounds reported herein do not display significant binding to the estrogen receptors. The inhibition of glucose uptake in cancer cells by these compounds was further observed by fluorescence microscopy imaging using a fluorescent analogue of glucose. Therefore, blocking the ability of tumor cells to take up glucose by means of these small molecules, or by further optimized derivatives, may be a successful approach in the development of novel anticancer drugs.     

MicroRNAs as Innovative Biomarkers for Inflammatory Bowel Disease and Prediction of Colorectal Cancer

Inflammatory bowel disease (IBD) includes ulcerative colitis (UC) and Crohn’s disease (CD). These are autoimmune diseases of the gastrointestinal tract with a chronic relapsing and remitting course. Due to complex interactions between multiple factors in the etiology of IBD, the discovery of new predictors of disease course and response to therapy, and the development of effective therapies is a significant challenge. The dysregulation of microRNAs (miRNAs), a class of conserved endogenous, small non-coding RNA molecules with a length of 18–25 nucleotides, that regulate gene expression by an RNA interference process, is implicated in the complex pathogenetic context of IBD. Both tissue-derived, circulating, and fecal microRNAs have been explored as promising biomarkers in the diagnosis and the prognosis of disease severity of IBD. In this review, we summarize the expressed miRNA profile in blood, mucosal tissue, and stool and highlight the role of miRNAs as biomarkers with potential diagnostic and therapeutic applications in ulcerative colitis and Crohn’s disease. Moreover, we discuss the new perspectives in developing a new screening model for the detection of colorectal cancer (CRC) based on fecal miRNAs.     

Visually impaired people and grocery shopping in store: First evidence from brain oscillations electroencephalogram

Grocery shopping represents a challenging task for visually impaired (VI), but the neuroscientific literature on the consumption patterns of this group is still scarce. The aim of the study was to analyse the relationship between explicit consumer experience and neuropsychological measures. A group of VI and sighted explored and manipulated three different product categories inside the supermarket, while EEG, behavioral and self-report data were collected. Electroencephalogram (EEG) findings showed a generalized delta band activity in pasta compared to frozen food and it was interpreted as higher emotional activation probably required by selecting the correct stimuli in a multisensory environment. A delta band activation was also found in frontal area in VI compared to control and it was supposed to be an index of greater cognitive control. Finally, higher delta band activity in parieto-occipital and temporal areas were related to greater sense of disorientation. In conclusion, it was found that VI experience grocery shopping more stressfully and with greater cognitive effort (parieto-occipital area) than people without visual disability. In general, VI use the sense of touch (temporal area) more and have more difficulties in orienting themselves internally in the store. The results could encourage the use of tactile touchpoints, braille maps, or an initial guided exploration of the supermarket, to allow the VI to memorize the internal layout of the different product categories and allow them to shop independently. Another suggestion would be to make products within the same product category more distinctive, perhaps by adding additional tactile information.     

Lysosomes Targeting pH Activable Imaging-Guided Photodynamic Agents

Photodynamic therapy (PDT) is a photochemistry-based medical treatment combining light at a specific wavelength and a photosensitizer (PS) in the presence of oxygen. Application of PDT as a conventional treatment is limited and clearly the approval in clinics of new PS is challenging. The selective accumulation of the PS in the targeted malignant cells is of paramount importance to reduce the side effects that are typical of the current worldwide approved PS. Here we report a new series of aniline- and iodine-substituted BODIPY derivatives ( 1 – 3 ) as promising lysosome-targeting and pH-responsive theranostic PS, which displayed a significant in vitro light-induced cytotoxicity, efficient imaging properties and low dark toxicity (for 2 and 3 ). These compounds were obtained in few reproducible synthetic steps and good yields. Spectroscopic and electrochemical measurements along with computational calculations confirmed the quenching of the emissive properties of the PS, while both fluorescence and ¹O₂ emission were obtained only under acidic conditions inducing amine protonation. The pK_a values and pH-dependent emissive properties of 1 – 3 being established, their cellular uptake and activation in the lysosomal vesicles (pH≈4-5) were confirmed by their co-localization with the commercial LysoTracker deep red and light-induced cytotoxicity (IC₅₀ between 0.16 and 0.06 μM) against HeLa cancer cells.     

Tools for monitoring toxicological and genotoxicological changes in a drinking water treatment plant in Northeast Italy

Drinking water quality can be compromised at different stages, from raw water to treated one. This research aimed to evaluate the toxicity and genotoxicity of groundwater contaminated by fluorinated compounds treated in a drinking water treatment plant, through several bioassays. Water samples underwent chemical analyses and were assayed on Daphnia magna, Pseudokirchneriella subcapitata, Allium cepa, human leukocytes and Salmonella typhimurium. Physical–chemical parameters were always within the Italian legislation limits. Water after filtration and disinfection caused slight toxicity in D. magna; the sample after filtration inhibited the proliferation of P. subcapitata. None of the water samples exerted toxicity in A. cepa. All the analysed samples had genotoxic effects on A. cepa and human leucocytes, while only disinfected water caused mutations in S. typhimurium. A battery composed of tests on D. magna, P. subcapitata, S. typhimurium and A. cepa could represent a useful tool to verify the toxicity/genotoxicity through the water treatment stages and to improve drinking water quality management.