Nanostructured Systems Containing Rutin: In Vitro Antioxidant Activity and Photostability Studies

The improvement of the rutin photostability and its prolonged in vitro antioxidant activity were studied by means of its association with nanostructured aqueous dispersions. Rutin-loaded nanocapsules and rutin-loaded nanoemulsion showed mean particle size of 124.30 ± 2.06 and 124.17 ± 1.79, respectively, polydispersity index below 0.20, negative zeta potential, and encapsulation efficiency close to 100%. The in vitro antioxidant activity was evaluated by the formation of free radical ·OH after the exposure of hydrogen peroxide to a UV irradiation system. Rutin-loaded nanostructures showed lower rutin decay rates [(6.1 ± 0.6) 10−3 and (5.1 ± 0.4) 10−3 for nanocapsules and nanoemulsion, respectively] compared to the ethanolic solution [(35.0 ± 3.7) 10−3 min−1] and exposed solution [(40.1 ± 1.7) 10−3 min−1] as well as compared to exposed nanostructured dispersions [(19.5 ± 0.5) 10−3 and (26.6 ± 2.6) 10−3, for nanocapsules and nanoemulsion, respectively]. The presence of the polymeric layer in nanocapsules was fundamental to obtain a prolonged antioxidant activity, even if the mathematical modeling of the in vitro release profiles showed high adsorption of rutin to the particle/droplet surface for both formulations. Rutin-loaded nanostructures represent alternatives to the development of innovative nanomedicines

Arachnoid cyst in a patient with psychosis: Case report

<p>Abstract</p> <p>Background</p> <p>The aetiology of a psychotic disturbance can be due to a functional or organic condition. Organic aetiologies are diverse and encompass organ failures, infections, nutritional deficiencies and space-occupying lesions. Arachnoid cysts are rare, benign space-occupying lesions formed by an arachnoid membrane containing cerebrospinal fluid (CSF). In most cases they are diagnosed by accident. Until recently, the coexistence of arachnoid cysts with psychiatric disturbances had not been closely covered in the literature. However, the appearance of some references that focus on a possible link between arachnoid cysts and psychotic symptoms has increased the interest in this subject and raised questions about the etiopathogeny and the therapeutic approach involved.</p> <p>Clinical presentation</p> <p>We present the clinical report of a 21-year-old man, characterised by the insidious development of psychotic symptoms of varying intensity, delusional ideas with hypochondriac content, complex auditory/verbal hallucinations in the second and third persons, and aggressive behaviour. The neuroimaging studies revealed a voluminous arachnoid cyst at the level of the left sylvian fissure, with a marked mass effect on the left temporal and frontal lobes and the left lateral ventricle, as well as evidence of hypoplasia of the left temporal lobe. Despite the symptoms and the size of the cyst, the neurosurgical department opted against surgical intervention. The patient began antipsychotic therapy and was discharged having shown improvement (behavioural component), but without a complete remission of the psychotic symptoms.</p> <p>Conclusion</p> <p>It is difficult to be absolutely certain whether the lesion had influence on the patient's psychiatric symptoms or not.</p> <p>However, given the anatomical and neuropsychological changes, one cannot exclude the possibility that the lesion played a significant role in this psychiatric presentation. This raises substantial problems when it comes to choosing a therapeutic strategy.</p

Recurring alcohol-related care between 1998 and 2007 among people treated for an alcohol-related disorder in 1997: A register study in Stockholm County

<p>Abstract</p> <p>Background</p> <p>Inpatient care for alcohol intoxication is increasing in Sweden, especially among young women. Since it is well known that alcohol disorder is a chronic relapsing illness, this study examines the extent to which people return for more care.</p> <p>Method</p> <p>All inpatients with alcohol-related diagnoses in Stockholm County during 1997 were followed prospectively to 2007 through registers. The proportion reappearing for the same diagnosis, other alcohol-related inpatient, or outpatient care each year after baseline, as well as the number of years the inpatients reappeared were calculated (n = 2735). Three diagnoses were examined separately; alcohol dependence, harmful use of alcohol, and alcohol intoxication.</p> <p>Results</p> <p>Three out of five inpatients with an alcohol diagnoses reappeared for more alcohol-related inpatient care during the following decade. The proportion returning was largest the year after baseline and then decreased curvilinearly over time. The inclusion of outpatient care increased proportions, but did not change patterns. Of those with an alcohol dependence diagnosis at baseline 42 percent returned for more alcohol-related inpatient care the first, 28 percent the fifth, and 25 percent the tenth year. Corresponding proportions for harmful use and intoxication were smaller. One in five among those with an alcohol dependence returned for more than five of the ten years. Ordered logistic regressions confirmed that besides diagnosis, age and gender were independently related to the number of years returning to care.</p> <p>Conclusions</p> <p>While middle-aged males with alcohol dependence were in a revolving door, young female inpatients with intoxication diagnosis returned to a comparably lower degree.</p

Transition from Positive to Neutral in Mutation Fixation along with Continuing Rising Fitness in Thermal Adaptive Evolution

It remains to be determined experimentally whether increasing fitness is related to positive selection, while stationary fitness is related to neutral evolution. Long-term laboratory evolution in Escherichia coli was performed under conditions of thermal stress under defined laboratory conditions. The complete cell growth data showed common continuous fitness recovery to every 2°C or 4°C stepwise temperature upshift, finally resulting in an evolved E. coli strain with an improved upper temperature limit as high as 45.9°C after 523 days of serial transfer, equivalent to 7,560 generations, in minimal medium. Two-phase fitness dynamics, a rapid growth recovery phase followed by a gradual increasing growth phase, was clearly observed at diverse temperatures throughout the entire evolutionary process. Whole-genome sequence analysis revealed the transition from positive to neutral in mutation fixation, accompanied with a considerable escalation of spontaneous substitution rate in the late fitness recovery phase. It suggested that continually increasing fitness not always resulted in the reduction of genetic diversity due to the sequential takeovers by fit mutants, but caused the accumulation of a considerable number of mutations that facilitated the neutral evolution

Sorafenib in patients with advanced biliary tract carcinoma: a phase II trial

BACKGROUND: Advanced biliary tract carcinoma has a very poor prognosis, with chemotherapy being the mainstay of treatment. Sorafenib, a multikinase inhibitor of VEGFR-2/-3, PDGFR-beta, B-Raf, and C-Raf, has shown to be active in preclinical models of cholangiocarcinoma. METHODS: We conducted a phase II trial of single-agent sorafenib in patients with advanced biliary tract carcinoma. Sorafenib was administered at a dose of 400 mg twice a day. The primary end point was the disease control rate at 12 weeks. RESULTS: A total of 46 patients were treated. In all, 26 (56%) had received chemotherapy earlier, and 36 patients completed at least 45 days of treatment. In intention-to-treat analysis, the objective response was 2% and the disease control rate at 12 weeks was 32.6%. Progression-free survival (PFS) was 2.3 months (range: 0-12 months), and the median overall survival was 4.4 months (range: 0-22 months). Performance status was significantly related to PFS: median PFS values for ECOG 0 and 1 were 5.7 and 2.1 months, respectively (P=0.0002). The most common toxicities were skin rash (35%) and fatigue (33%), requiring a dose reduction in 22% of patients. CONCLUSIONS: Sorafenib as a single agent has a low activity in cholangiocarcinoma. Patients having a good performance status have a better PFS. The toxicity profile is manageable

TRY plant trait database - enhanced coverage and open access

Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives

Proteomics as a Method for Early Detection of Cancer: A Review of Proteomics, Exhaled Breath Condensate, and Lung Cancer Screening

The study of expressed proteins in neoplasia is undergoing a revolution with the advent of proteomic analysis. Unlike genomic studies where individual changes may have no functional significance, protein expression is closely aligned with cellular activity. This perspective will review proteomics as a method of detecting markers of neoplasia with a particular emphasis on lung cancer and the potential to sample the lung by exhaled breath condensate (EBC). EBC collection is a simple, new, and noninvasive technique, which allows sampling of lower respiratory tract fluid. EBC enables the study of a wide variety of biological markers from low molecular weight mediators to macromolecules, such as proteins, in a range of pulmonary diseases. EBC may be applied to the detection of lung cancer where it could be a tool in early diagnosis. This perspective will explore the potential of applying proteomics to the EBC from lung cancer patients as an example of detecting potential biomarkers of disease and progression

Direct Ubiquitin Independent Recognition and Degradation of a Folded Protein by the Eukaryotic Proteasomes-Origin of Intrinsic Degradation Signals

Eukaryotic 26S proteasomes are structurally organized to recognize, unfold and degrade globular proteins. However, all existing model substrates of the 26S proteasome in addition to ubiquitin or adaptor proteins require unstructured regions in the form of fusion tags for efficient degradation. We report for the first time that purified 26S proteasome can directly recognize and degrade apomyoglobin, a globular protein, in the absence of ubiquitin, extrinsic degradation tags or adaptor proteins. Despite a high affinity interaction, absence of a ligand and presence of only helices/loops that follow the degradation signal, apomyoglobin is degraded slowly by the proteasome. A short floppy F-helix exposed upon ligand removal and in conformational equilibrium with a disordered structure is mandatory for recognition and initiation of degradation. Holomyoglobin, in which the helix is buried, is neither recognized nor degraded. Exposure of the floppy F-helix seems to sensitize the proteasome and primes the substrate for degradation. Using peptide panning and competition experiments we speculate that initial encounters through the floppy helix and additional strong interactions with N-terminal helices anchors apomyoglobin to the proteasome. Stabilizing helical structure in the floppy F-helix slows down degradation. Destabilization of adjacent helices accelerates degradation. Unfolding seems to follow the mechanism of helix unraveling rather than global unfolding. Our findings while confirming the requirement for unstructured regions in degradation offers the following new insights: a) origin and identification of an intrinsic degradation signal in the substrate, b) identification of sequences in the native substrate that are likely to be responsible for direct interactions with the proteasome, and c) identification of critical rate limiting steps like exposure of the intrinsic degron and destabilization of an unfolding intermediate that are presumably catalyzed by the ATPases. Apomyoglobin emerges as a new model substrate to further explore the role of ATPases and protein structure in proteasomal degradatio