Worsening of the Toxic Effects of (±)Cis-4,4′-DMAR Following Its Co-Administration with (±)Trans-4,4′-DMAR: Neuro-Behavioural,Physiological, Immunohistochemical and Metabolic Studies in Mice

4,4’-Dimethylaminorex (4,4’-DMAR) is a new synthetic stimulant, and only a little information has been made available so far regarding its pharmaco-toxicological effects. The aim of this study was to investigate the effects of the systemic administration of both the single (±)cis (0.1–60 mg/kg) and (±)trans (30 and 60 mg/kg) stereoisomers and their co-administration (e.g., (±)cis at 1, 10 or 60 mg/kg + (±)trans at 30 mg/kg) in mice. Moreover, we investigated the effect of 4,4′-DMAR on the expression of markers of oxidative/nitrosative stress (8-OHdG, iNOS, NT and NOX2), apoptosis (Smac/DIABLO and NF-κB), and heat shock proteins (HSP27, HSP70, HSP90) in the cerebral cortex. Our study demonstrated that the (±)cis stereoisomer dose-dependently induced psychomotor agitation, sweating, salivation, hyperthermia, stimulated aggression, convulsions and death. Conversely, the (±)trans stereoisomer was ineffective whilst the stereoisomers’ co-administration resulted in a worsening of the toxic (±)cis stereoisomer effects. This trend of responses was confirmed by immunohistochemical analysis on the cortex. Finally, we investigated the potentially toxic effects of stereoisomer co-administration by studying urinary excretion. The excretion study showed that the (±)trans stereoisomer reduced the metabolism of the (±)cis form and increased its amount in the urine, possibly reflecting its increased plasma levels and, therefore, the worsening of its toxicity.     

Mechanistic study of C12 evolution at Ti-supported Co3O4 anodes

Co₃O₄ layers were prepared by thermal decomposition of Co(NO₃)₂ at various temperatures in the range 200–500° C on a Ti support with and without an interlayer of RuO₂. Kinetic studies were carried out with and without dissolved Cl₂ at various partial pressures in NaCl solutions of concentration in the range 0.5–5 mol dm^–3. The effect of the solution pH was especially investigated. Kinetic measurements were carried out both close to and far from equilibrium. The following parameters were determined: transfer coefficient, Tafel slope, stoichiometric number, reaction orders with respect to Cl^–, H⁺ and surface sites, activation energy. The most intriguing feature observed was the retarding effect of acidity on the anodic Cl₂ reaction. This has been ascribed to the complex surface behaviour of oxides in solution. A detailed mechanistic scheme has been proposed and discussed. The stability of the oxide surface was monitored by measuring the voltammetric charge in alkaline solution after sets of experiments.Paper presented at the 34th Meeting of the International Society of Electrochemistry, Erlangen, 19–23 September, 1983.     

Physical properties and water state changes during storage in soy bread with and without almond

Soy bread was formulated to impart different isoflavone profiles by addition of almond: a natural source of β-glucosidase. In this study, the influence of almond powder on loaf quality and storage stability of soy bread was investigated using thermal analysis, texture, loaf volume and air cell imaging techniques. Lipids introduced with the almond fraction, served as mediators to strengthen the interaction between wheat and soy protein, thereby increasing dough extensibility. Loaf quality of the almond soy bread was therefore improved since the collapse of air cells during bread preparation was prevented. This in turn favored better loaf quality. Additionally, water binding strength and changes thereof during storage, probed by thermal analysis, were found to significantly hinder the staling rate during prolonged storage of soy-containing breads.     

Peripheral neuropathy in scleroderma

The diagnostic relevance of recording motor evoked potentials (MEPs) after electrical stimulation of the cervical region, as compared with conventional needle electromyography (EMG), was evaluated in 26 patients with brachial plexus (BP) damage of different aetiology, severity and topography. MEP abnormalities (absence or latency increase) were observed in at least one muscle of all the patients, with a global incidence of 61.5% of the muscles examined. Neurogenic EMG signs were present in all but one patient with an incidence of 62.2% of the muscles examined. Combining the two methods, the global incidence of abnormalities rose to 69.9%. MEP abnormalities were consistent with the clinical topography and severity of BP lesions and were fairly parallel with EMG findings. Recording MEPs after percutaneous electrical stimulation of the cervical region may be regarded as a rapid, non-invasive method for quantitative electrophysiological assessment of BP damage.     

Random access in a list environment

A memory allocation scheme for list structures (ral system) is proposed, which allows random access and search for the elements of the structure. A comparative study of classical list systems and ral systems is given, for the basic operations of search, insertion, deletion and sorting of the structure elements. It is shown that, in general, ral systems exhibit lower order expected time complexities for such operations, possibly at the expense of a reasonable increase in memory occupation. Allocation and processing of linear ordered lists and trees are discussed in particular.     

SLA-Driven Clustering of QoS-Aware Application Servers

In this paper, we discuss the design, implementation, and experimental evaluation of a middleware architecture for enabling service level agreement (SLA)-driven clustering of QoS-aware application servers. Our middleware architecture supports application server technologies with dynamic resource management: application servers can dynamically change the amount of clustered resources assigned to hosted applications on-demand so as to meet application-level quality of service (QoS) requirements. These requirements can include timeliness, availability, and high throughput and are specified in SLAs. A prototype of our architecture has been implemented using the open-source J2EE application server JBoss. The evaluation of this prototype shows that our approach makes possible JBoss' resource usage optimization and allows JBoss to effectively meet the QoS requirements of the applications it hosts, i.e., to honor the SLAs of those applications     

Current awareness on yeast

In order to keep subscribers up-to-date with the latest developments in their field, this current awareness service is provided by John Wiley & Sons and contains newly-published material on yeasts. Each bibliography is divided into 10 sections. 1 Books, Reviews & Symposia; 2 General; 3 Biochemistry; 4 Biotechnology; 5 Cell Biology; 6 Gene Expression; 7 Genetics; 8 Physiology; 9 Medical Mycology; 10 Recombinant DNA Technology. Within each section, articles are listed in alphabetical order with respect to author. If, in the preceding period, no publications are located relevant to any one of these headings, that section will be omitted. (4 weeks journals - search completed 16th Feb 2000)     

Clinical and Functional Study of a De Novo Variant in the PVP Motif of Kv1.1 Channel Associated with Epilepsy,Developmental Delay and Ataxia

Mutations in the KCNA1 gene, encoding the voltage-gated potassium channel Kv1.1, have been associated with a spectrum of neurological phenotypes, including episodic ataxia type 1 and developmental and epileptic encephalopathy. We have recently identified a de novo variant in KCNA1 in the highly conserved Pro-Val-Pro motif within the pore of the Kv1.1 channel in a girl affected by early onset epilepsy, ataxia and developmental delay. Other mutations causing severe epilepsy are located in Kv1.1 pore domain. The patient was initially treated with a combination of antiepileptic drugs with limited benefit. Finally, seizures and ataxia control were achieved with lacosamide and acetazolamide. The aim of this study was to functionally characterize Kv1.1 mutant channel to provide a genotype–phenotype correlation and discuss therapeutic options for KCNA1-related epilepsy. To this aim, we transfected HEK 293 cells with Kv1.1 or P403A cDNAs and recorded potassium currents through whole-cell patch-clamp. P403A channels showed smaller potassium currents, voltage-dependent activation shifted by +30 mV towards positive potentials and slower kinetics of activation compared with Kv1.1 wild-type. Heteromeric Kv1.1+P403A channels, resembling the condition of the heterozygous patient, confirmed a loss-of-function biophysical phenotype. Overall, the functional characterization of P403A channels correlates with the clinical symptoms of the patient and supports the observation that mutations associated with severe epileptic phenotype cluster in a highly conserved stretch of residues in Kv1.1 pore domain. This study also strengthens the beneficial effect of acetazolamide and sodium channel blockers in KCNA1 channelopathies.     

The Presence of Blood–Brain Barrier Modulates the Response to Magnesium Salts in Human Brain Organoids

Magnesium (Mg) is fundamental in the brain, where it regulates metabolism and neurotransmission and protects against neuroinflammation. To obtain insights into the molecular basis of Mg action in the brain, we investigated the effects of Mg in human brain organoids, a revolutionary 3D model to study neurobiology and neuropathology. In particular, brain organoids derived from human induced pluripotent stem cells were cultured in the presence or in the absence of an in vitro-generated blood–brain barrier (BBB), and then exposed to 1 or 5 mM concentrations of inorganic and organic Mg salts (Mg sulphate (MgSO₄); Mg pidolate (MgPid)). We evaluated the modulation of NMDA and GABAergic receptors, and BDNF. Our data suggest that the presence of the BBB is essential for Mg to exert its effects on brain organoids, and that 5 mM of MgPid is more effective than MgSO₄ in increasing the levels of GABA receptors and BDNF, and decreasing those of NMDA receptor. These results might illuminate novel pathways explaining the neuroprotective role of Mg.