A highly selective colorimetric chemodosimeter for thiol-containing compounds in aqueous solutions is reported. The design protocol makes use of a highly specific reaction between thiols and the electrophilic four-membered ring of highly colored, fluorescent squaraine backbones. At neutral pH selective decoloration and total emission quenching was found due to the rupture of the highly delocalized squaraine framework upon selective nucleophilic addition of thiol-containing derivatives. The squaraine derivatives have been successfully applied to the determination of low-molecular mass aminothiols in human plasma. The method utters the high potential applicability of the chemodosimeter approach in the search for new or improved chromogenic selective or specific probes for target guests.

Peroxynitrite toxicity is a major cause of neuronal injury in stroke and neurodegenerative disorders. The mechanisms underlying the neurotoxicity induced by peroxynitrite are still unclear. In this study, we observed that TPEN [N,N,NЈ,NЈ-tetrakis (2-pyridylmethyl)ethylenediamine], a zinc chelator, protected against neurotoxicity induced by exogenous as well as endogenous (coadministration of NMDA and a nitric oxide donor, diethylenetriamine NONOate) peroxynitrite. Two different approaches to detecting intracellular zinc release demonstrated the liberation of zinc from intracellular stores by peroxynitrite. In addition, we found that peroxynitrite toxicity was blocked by inhibitors of 12-lipoxygenase (12-LOX), p38 mitogen-activated protein kinase (MAPK), and caspase-3 and was associated with mitochondrial membrane depolarization. Inhibition of 12-LOX blocked the activation of p38 MAPK and caspase-3. Zinc itself induced the activation of 12-LOX, generation of reactive oxygen species (ROS), and activation of p38 MAPK and caspase-3. These data suggest a cell death pathway triggered by peroxynitrite in which intracellular zinc release leads to activation of 12-LOX, ROS accumulation, p38 activation, and caspase-3 activation. Therefore, therapies aimed at maintaining intracellular zinc homeostasis or blocking activation of 12-LOX may provide a novel avenue for the treatment of inflammation, stroke, and neurodegenerative diseases in which the formation of peroxynitrite is thought to be one of the important causes of cell death.

A new chromo-chemodosimeter for the anion sulfide in aqueous environments has been developed. The recognition concept is based on a pyrylium-thiopyrylium transformation that is conveniently drawn toward "color chemistry" concepts by means of the anchoring of an aniline group. This causes the color of the aniline-pyrylium backbone in L1 to change selectively from magenta to blue when transformed to the corresponding aniline-thiopyrylium in the presence of the sulfide anion. The method is simple and easy, suggesting potential applications in a variety of different environments where easy and rapid determination of sulfide might be required.

The development of mining activities in North Chile involves a great number of workers intermittently exposed to high altitude for a long period of time (chronic intermittent hypoxia, CIH). A 2(1/2)-year prospective study aimed to characterize this model of exposure to CIH and to know whether this condition may progressively lead to a chronic pattern. Twenty-nine miners, aged 25 +/- 5 yr, working 7 days at HA (3800 to 4600 m) and resting 7 days at sea level (SL) were studied. Subjects underwent a physical examination, EKG, hematological status, maximal exercise test, ventilatory and cardiac response to hypoxia (F(iO2) = 0.114) at rest and exercise, pulmonary vascular response to hypoxia by echocardiography, and 24-h monitoring of EKG and arterial pressure. Basal evaluations were performed at SL before the first exposure to hypoxia. HA measurements were daily AMS score, sleep status, and 24-h monitoring of EKG and arterial pressure. All these measurements were repeated after a mean period of 12, 19, and 31 months. Hematocrit increased but reached values lower than those observed in chronic permanent exposure. Systemic and pulmonary arterial pressures measured at SL did not change, but were higher in hypoxia. Right ventricle showed a slight dilatation. Exercise performance at SL declined with exposure to CIH to reach a 12.3% decrease after 31 months of CIH, associated with a 6.8% decrease in maximal heart rate. Signs of ventilatory acclimatization were observed after 12 months. Symptoms of AMS and sleep disturbances were still seen on the first 2 days at HA, whatever the time of exposure to CIH. In conclusion, CIH induced a clear acclimatization process. Subjects did not reach a health status comparable to that seen in permanent residents at HA and remained at risk of acute altitude-induced illnesses.

There is an increasing role for biological markers (biomarkers) in the understanding and diagnosis of neurodegenerative disorders. The application of imaging biomarkers specifically for the in vivo investigation of neurodegenerative disorders has increased substantially over the past decades and continues to provide further benefits both to the diagnosis and understanding of these diseases. This review forms part of a series of articles which stem from the University College London/University of Gothenburg course "Biomarkers in neurodegenerative diseases". In this review, we focus on neuroimaging, specifically positron emission tomography (PET) and magnetic resonance imaging (MRI), giving an overview of the current established practices clinically and in research as well as new techniques being developed. We will also discuss the use of machine learning (ML) techniques within these fields to provide additional insights to early diagnosis and multimodal analysis.