Temperature Enhancement of Thermal Hall Conductance Quantization.

The quest for non-Abelian quasiparticles has inspired decades of experimental and theoretical efforts, where the scarcity of direct probes poses a key challenge. Among their clearest signatures is a thermal Hall conductance with quantized half-integer value in units of κ_{0}=π^{2}k_{B}^{2}T/3h (T is temperature, h the Planck constant, k_{B} the Boltzmann constant). Such values were recently observed in a quantum-Hall system and a magnetic insulator. We show that nontopological "thermal metal" phases that form due to quenched disorder may disguise as non-Abelian phases by well approximating the trademark quantized thermal Hall response. Remarkably, the quantization here improves with temperature, in contrast to fully gapped systems. We provide numerical evidence for this effect and discuss its possible implications for the aforementioned experiments.

Localization Counteracts Decoherence in Noisy Floquet Topological Chains.

The topological phases of periodically driven, or Floquet systems, rely on a perfectly periodic modulation of system parameters in time. Even the smallest deviation from periodicity leads to decoherence, causing the boundary (end) states to leak into the system's bulk. Here, we show that in one dimension this decay of topologically protected end states depends fundamentally on the nature of the bulk states: a dispersive bulk results in an exponential decay, while a localized bulk slows the decay down to a diffusive process. The localization can be due to disorder, which remarkably counteracts decoherence even when it breaks the symmetry responsible for the topological protection. We derive this result analytically, using a novel, discrete-time Floquet-Lindblad formalism and confirm our findings with the help of numerical simulations. Our results are particularly relevant for experiments, where disorder can be tailored to protect Floquet topological phases from decoherence.

Aperiodic Weak Topological Superconductors.

Weak topological phases are usually described in terms of protection by the lattice translation symmetry. Their characterization explicitly relies on periodicity since weak invariants are expressed in terms of the momentum-space torus. We prove the compatibility of weak topological superconductors with aperiodic systems, such as quasicrystals. We go beyond usual descriptions of weak topological phases and introduce a novel, real-space formulation of the weak invariant, based on the Clifford pseudospectrum. A nontrivial value of this index implies a nontrivial bulk phase, which is robust against disorder and hosts localized zero-energy modes at the edge. Our recipe for determining the weak invariant is directly applicable to any finite-sized system, including disordered lattice models. This direct method enables a quantitative analysis of the level of disorder the topological protection can withstand.

The effect of caffeine on cerebral asymmetry in rats.

EEG recordings reflect the gross electrical activity emanating from synaptic currents of individual neurons across large cortical areas. During periods of cortical activation, waking, and higher EEG frequencies, neurons display increased excitability and exhibit more asynchronous discharge. The activity of a number of subcortical neurotransmitter systems from several brain regions outside the thalamus can directly affect cortical activity patterns. These neurotransmitter systems are generally targets of pharmacological intervention or participate in neurological disease states. The EEG trace comprises 4 primary rhythms: alfa (α), beta (ß), theta (θ) and delta (δ), which differ in frequency and amplitude. Caffeine effect on brain asymmetry will be studied in this work. The study was realized by means of Fourier spectral frequency analysis (Fast Fourier Transformation) of the EEG signal on anesthetized rats. All 3 doses of caffeine increased the global wave power of brain activity compared to the control group. All 3 doses of caffeine reduced the number of peaks for the 0.5-4 Hz frequency band, with the intermediate dose of caffeine having such an effect in the 4-7 Hz frequency band and the high dose of caffeine for the 23-33 Hz frequency band. The group that received high doses of caffeine showed an increase of the percentage of delta waves, with a concurrent decrease of the percentage of alpha1, alpha2, beta and theta 2 compared to the control group. Low-dose caffeine produced positive values of left-right difference in brain electrical activity (left predominance) for the 0.5-5 Hz and 7.8-10.3 Hz frequency intervals. The group that received high-dose caffeine exhibited a left hemisphere dominance for the 0.5-1.5 Hz; 13.9-14.1 Hz and 19-20 Hz frequency ranges while right dominance was present in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges. In conclusion, all doses of caffeine modified the global power of the brain as well as the number of peaks on the frequency range of 0.5-4 Hz. The higher dose of caffeine modified the percentage of alpha 1, alpha2, beta, delta and theta2 waves compared to the control group. The group that received 150 mg caffeine/ kg.b.w. recorded a reversal in the cerebral asymmetry of rats in the 1.7-13.9 Hz, 15-19 Hz and 21-25 Hz frequency ranges.

Molecular and pharmacodynamic interactions between caffeine and dopaminergic system.

Many drugs targeting dopaminergic system were developed for treating schizophrenia (antagonists of D2 dopaminergic receptors, e.g. antipsychotics) or Parkinson' disease (agonists of dopaminergic receptors, e.g. L-DOPA). Because many of the patients treated with these drugs consume caffeine based beverages, pharmacodynamics and pharmacokinetics interactions between caffeine and dopaminergic system or drugs influencing this system are possible. The present review is assessing the current available scientific data on pharmacodynamics interactions between the dopaminergic and adenosinergic system but also on caffeine and dopaminergic system interactions. Caffeine can significantly improve Parkinson's disease symptoms but also the extrapyramidal syndrome induced by antipsychotics via dopaminergic pathways. No study so far has directly evaluated the influence of caffeine in schizophrenia, but there is growing evidence that adenosine dysfunction may contribute to the neurobiological and clinical features of schizophrenia. Caffeine has also effects on the reward system but it seems that this effect does not involve dopaminergic system. Caffeine has some endocrine effects via dopaminergic system such as decreasing the milk production in lactating women or other potential reproductive and nutritional consequences.

Hepcidin in neoplastic disease.

Abnormalities in iron metabolism are frequent in the neoplastic disease. The relationship between hepcidin and iron homeostasis in cancerous pathology is incompletely known, although it has been studied during the last years. This paper aims to analyze the role of hepcidin in the neoplastic processes, its correlation with carcinogenesis and anemia, and with the disease activity. It must be mentioned that most of the aspects presented need to be verified in practice. Insufficient data are known for showing hepcidin involvement in carcinogenesis, metastasis or in appreciating the response to anemia treatment in neoplasia.

Major omphalocele with liver protrusion. Liver dysmorphism. A case study.

In the Renaissance (1634), Ambroise Paré described for the first time the omphalocele, highlighting the serious prognosis of this malformation. The incidence of omphalocele varies between 1/2000-1/6000 births, both sexes being equally affected. We present the case of a male infant, born at term after a pregnancy that was not followed by the family doctor or by the specialist obstetrician and who died after five days. On the anterior abdominal wall in the umbilical region, there was a formation of about 10 cm in diameter, covered by a membrane apparently avascular through whose transparency there could be observed a blue-reddish tumor, of discreet firm consistency that while breathing compressed the apparently avascular membrane that covers it. Intraoperative there was noticed liver herniation by parietal defect, operating the liver reintegration in umbilical cavity, subsequently the child dying from a cardio-respiratory arrest. The particularity of this case is on one hand the liver herniation without intestinal loops, the most common liver hernia being with intestinal loops and, on the other hand the presence of hepatic dysmorphism. We also mention the trilaminar structure of omphalocele membrane sac, which makes us think that the herniation was secondary, after the tenth week, through a defect of the anterior abdominal wall closure in the umbilicus region. The combination of these elements creates the uniqueness of this case.

Local tolerability and effectiveness of Ketospray® 10% cutaneous spray solution.

BACKGROUND: Orally administrated nonsteroidal anti-inflammatory drugs are effective in the treatment of a variety of acute and chronic pain conditions but their use may be associated with serious systemic adverse effects which are correlated with the therapeutic plasma levels of the drug. In order to minimize the incidence of drug related systemic events, topical formulations of the nonsteroidal anti-inflammatory drugs have been developed. A recently performed review of the evidence from randomized, double-blind, placebo controlled trials with topically applied NSAIDs in the treatment of acute pain confirmed the previously described pain relief effectiveness. For all topical nonsteroidal anti-inflammatory drugs combined, in comparison to placebo, the number needed to treat (NNT) to achieve a clinically meaningful pain relief of 50 % was 4.5 (3.9 to 5.3) for treatment periods of 6 to 14 days. Local skin reactions were generally mild and transient, and did not differ from placebo. OBJECTIVES: The present is an observational, multicenter, open-label, non-interventional, post-authorization safety study as it is defined by Article 21 of the European Clinical Trials Directive 2001/20/EC. The main objective of this study was to evaluate the local tolerability and the therapeutic efficacy of static and pain on movement intensity reduction of Ketospray® 10% cutaneous spray solution administered in accordance with the terms of the marketing authorization and last version of summary of product characteristics approved by National Medicines Agency of Romania. METHODS: In compliance with the Post-marketing study type, the assignment of the patient to a particular therapeutic strategy fell within current practice. The prescription of the medicine was not subject to compliance with predefined patients' characteristics. No specific, out of the daily practice routine diagnostic, monitoring, instrumental or laboratory assessments were foreseen by the study protocol. Patients' data were collected into respective case report forms. Study medication, Ketoprofen 10% Cutaneous Spray Solution was administered to the affected area at the dose of 3-6 spray puffs, 2-3 times a day, for 7 days. According to the study type, descriptive statistical methods were applied. Since almost half of the patients were treated with combination of the pain relieving medications, sizing of the pain relieving effects, as NNT, between the two groups was made. FINDINGS: There were 2020 study subjects in safety and ITT analysis population and 1802 (89%) in PP efficacy analysis population. There were 4 types of injuries: non-complicated strain-sprain (555), soft tissue contusion (323), low back pain (461) and osteoarthritis (681 patients). Ten patients reported 13 side effects of which 10 were recognized by investigators as adverse drug reactions. All side effects were non-serious, listed, application site skin changes. Remarkable reductions of static and pain on movement intensity were experienced by patients irrespective of the type of the injury and the type of the treatment. However, a clinically meaningful benefit of the concomitantly prescribed pain relieving medications was not observed for any type of pain. The lowest NNT (14) was obtained for the reduction of pain at rest in patients with strain-sprain or soft tissue contusions. The highest NNT (283) was for pain at rest in patients treated for the exacerbation of the chronic pain. CONCLUSIONS: The results of the current post-authorization study confirm beneficial pain intensity reducing efficacy of Ketospray 10% associated with good local tolerability of 7 days treatment course. Concomitant administration of systemic pain relieving medication did not substantially contribute neither to the relief of pain at rest nor of pain on movement among the subjects of respective study populations.

Cannabinoid system and cyclooxygenases inhibitors.

RATIONALE: The cannabinoid system consists of a complex array of receptors, substances with agonist/antagonist properties for those receptors, biosynthetic machineries and mechanisms for cellular uptake and degradation for endocannabinoids. This system is in interrelation with other systems that comprise lipid mediators like prostaglandins/leukotrienes systems. A clear antagonist, additive or synergic effect of nonsteroidal anti-inflammatory drugs (NSAIDs)-cannabinoid associations was not yet demonstrated. Aim. The present study tried to summarize the existent data on NSAIDS-cannabinoid system interactions. METHODS AND RESULTS: A bibliographic research in Medline, Scirus, Embase was made using as keywords cannabinoid, nonsteroidal anti-inflammatory drugs, aspirin, ibuprofen, flurbiprofen, diclofenac, indomethacin, acetaminophen, coxibs, antinociceptive, antinociception, analgesia DISCUSSIONS: A systematization of the results focusing on the NSAIDs drugs interaction with the cannabinoid system was presented. Out of all the substances analyzed in the present review, acetaminophen was studied the most regarding its interferences with the cannabinoid system, mainly due to contradictory results. CONCLUSIONS: Some NSAIDs have additional influences on the cannabinoid system either by inhibiting fatty acid amide hydrolase (FAAH) or by inhibiting a possible intracellular transporter of endocannabinoids. All the NSAIDs that inhibit COX2 can influence the cannabinoid system because a possible important degradative pathway for anandamide and 2-arachidonoyl glycerol might involve COX 2. One of the causes for the variety of experimental results presented might be due to pharmacokinetic mechanisms, depending on the route of administration and the dose

VEGF-induced corneal neovascularisation in a rabbit experimental model.

INTRODUCTION AND PURPOSE: Various conditions may cause vascularization of the normally avascular cornea. The aim of the present study was to create a reproducible experimental model that could enable the investigation of the phenomena leading to corneal vascularization. This involved creating a software to record the experimental data, enabling a subsequent digital analysis based on the growth models. The VEGF-induced pattern of neovascularization was also investigated. MATERIAL AND METHODS: Twenty-seven rabbits divided in groups were used for the purposes of the present study. Some of them underwent intracorneal implants with or without vascular endothelial growth factor (VEGF) pellets, using an original microsurgical technique. Central and peripheral corneal burns were induced to other groups of animals in order to mimic the neovascularization process induced by inflammation. Finally, Dexamethasone (Maxidex) was given intraocularly, on days 1 and 3 after the onset of neovascularisation, in rabbit groups with both corneal burns and VEGF-implants. Video recording and data analysis of the corneal vascularization were made with an advanced biomicroscope, a computerized imaging system and a special software. A histochemical study of the animals' eyes was also carried out. RESULTS AND DISCUSSION: The recorded data showed the simplicity and reproducibility of the present experimental model. The results showed the importance of VEGF as an initiator and promoter of corneal vascularization through a non-inflammatory mechanism, quite different from the inflammation illustrated by the corneal burn. At the same time, Dexamethasone therapy proved its effectiveness in corneal angiogenesis induced by thermal burn, but not by VEGF-implant.

Beta 3 adrenergic receptors: molecular, histological, functional and pharmacological approaches.

Different classes of receptors mediate norepinephrine and epinephrine effects, one of the most recently discovered being the beta 3 adrenergic ones. The paper has proposed itself to present the history of the discovery of beta 3 adrenergic receptors, different techniques for their identification, their structure, localization, genetic data and also the mechanism of regulation of their functions. It also contains an exhaustive approach regarding the histological localization and functions of beta 3 adrenergic receptors in different apparatus and systems, making evident their effect on glucidic, lipidic and energetic metabolism. The substances that influence beta 3 adrenergic receptors activities, especially the agonists, have been studied regarding their practical applications in the treatment of diabetes mellitus and of the disturbances of lipid metabolism.

Particularities of vascular reactivity of the conjunctiva and iris in rats.

Considering that the conjunctiva and iris are developed from different embryological origins, an analysis of any possible differences in the density and type of adrenoceptors between these two areas was tried. An experimental study on male adult Wistar rats was performed. Six groups (six rats per group) were used by recording the iris and conjunctival vessels after eye instillations with solutions of adrenaline 0.1%, isoprenaline chlorhydrate 0.00002% and distilled water. The image analyze were carried out using VirtualDub 1.5.1 and Adobe PhotoShop 6.0., measuring the variations of the vessels diameters before and after the solutions instillations at fixed time intervals. The means of each eye values were compared with the control value using a statistical significance T test. The analysis of the two groups treated with adrenaline 0.1% showed a different reactivity of the vessels from the conjunctiva and iris, respectively. The iris vessels performed a gradual vasoconstriction. On the contrary, the conjunctival vessels showed initially mild, but significant vasodilatation, while vasoconstriction started later and was not as intense as for the iris vessels. The iris vessels treated with isoprenaline 0.00002% showed no significant changes in the vascular diameters. On the contrary, the conjunctival vessels showed a significant vasodilatation. The differences in the vascular reactivity of the two ocular areas (conjunctiva and iris) to vasoactive amines (epinephrine, isoprenaline) support the idea that beta 2 adrenergic receptors are present only in conjunctiva vessels but not in iris vessels, while alpha adrenoceptors are present in both vascular territories.

Influencing vascular reactivity in vivo by histaminergic agonists and antagonists.

The eye is a target organ for the action of several topical or systemic drugs. The aim of the present study is to analyze the differences in reactivity between the iris and conjunctiva vessels after the topical administration of histamine and histamine receptor blockers respectively. Using a novel non-invasive technique for the quantification of the vascular diameters in the eye vessels, the response of these vessels to histamine, to H1 receptor blocker promethazine, and to H2 receptor blocker ranitidine versus vehicle (control) was analyzed. The results show differences in reactivity between iris and conjunctiva vascular territories. This data suggest that the population of histamine receptors differs between these two vascular areas.

[Effects of serotonin on reactivity of ocular vasculature]. / Efectele serotoninei asupra reactivitatii vasculare oculare.

INTRODUCTION: Serotonin presents specific receptors of many types and subtypes. The aim of this study was to analyze the differences in reactivity between the vessels (arteries and veins) of the iris and conjunctiva. The vascular diameter was measured using a noninvasive technique after intraocular administration of different doses of serotonin. MATERIAL AND METHODS: The tests were performed on rats, divided in control and study groups. The modifications of studied vessels' diameters before and after topical administration of the solutions were evaluated by measuring these diameters at fixed time intervals of 30 seconds, for 6 minutes. Differentiation between arteries and veins was made using topical administration of felodipine after the testing 6 minutes interval The statistical significance of differences between the values obtained in each interval of 30 seconds and the control values at the initial moment was evaluated using t-test, the "paired" variant. RESULTS: There were obtained differences in reactivity between iris and conjunctival vessels and between iris arteries and veins for the different concentrations of tested serotonin solutions. CONCLUSIONS: Iris and conjunctival vessels contain serotonin receptors with different types and densities, whose activation produced vasoconstriction in both territories, but with different evolution and intensity. Differences in reactivity were found between iris arteries and veins, probably due to a different density of receptors between those two territories. The different vascular response might be a protective mechanism against dissemination of conjunctival infections.

The analgesic effect of gemcitabine in mice.

The analgesic effect of gemcitabine was analyzed in two experimental tests in mice. In the first test gemcitabine produced a dose-dependent decrease of the number of torsions produced by i.p. acetic acid in mice proving an analgesic effect. In the hot plate test the gemcitabine produced a non-statistical significant increase of the latency of the leakage, but a statistically significant increase of the latency of the salt proving an analgesic effect produced especially by a nervous central mechanism like morphine. The association of the gemcitabine and morphine proved that an inactive dose of gemcitabine increased statistically significant the effect of morphine proving a potentiation of the effect of morphine by gemcitabine. A same potentiation was demonstrated also by an effective analgesic dose of gemcitabine. The analgesic effect of the gemcitabine was antagonized by aminophiline, an inhibitor of the phosphodiesteraze, proving that the analgesic effect of the gemcitabine could be produced by a decrease of the intracellular cAMP. According to the chemical structure of gemcitabine it is possible that gemcitabine decrease the velocity of the degradation of the GMP fixed on the alpha subunit of the Gi protein and so increase the effect of the activated a subunit of the Gi protein to inactivate the adenylatecyclase. The analgesic effect of gemcitabine could be important in clinical management of antineoplastic patient by increasing the quality of life of these patients and the property of gemcitabine to potentiate the analgesic effect of morphine could be important by decreasing the needs of morphine of the antineoplastic patients. More researches will be necessary for evaluating also other nervous central effects of gemcitabine, for evaluation if other antineoplastic drugs have the same effect and for establishing a possible chemical structure-analgesic effect relationship and maybe also for evaluation if other effects of morphine are potentiated by gemcitabine and other antineoplastic drugs.

Effect of kanamycin and gentamicin on frog n. sciatic--m. gastrocnemian preparation.

The effect of kanamycin and gentamicin on frog n.sciatic-m.gastrocnemian preparatus was analyzed. Both substances decreased the muscular contraction in both after direct electrical stimulation of the muscle and electrical nerve stimulation, in a dose-dependent manner. Both substances were used at a concentration near the therapeutical concentration in human. The effect of kanamycin was more important than the effect of gentamicin. These data obtained in presented experimental condition are in accord with clinical observation but are not in accord with the possibility that aminoglycoside antibiotics block presynaptic Ca2+ channels.

Comparison of an adenosine A1 receptor agonist and antagonist on the rat EEG.

The effects of the selective adenosine A1 receptor agonist N6-cyclopentyladenosine (CPA; 1 and 0.1 mg/kg, i.p.) and the A1 selective antagonist 8-cyclopentyl-1,3-dipropylxanthine (CPX) have been examined on the electroencephalogram (EEG) of intact rats. From four EEG leads the EEG signal was subjected to Fast Fourier Transform and analysed both in narrow (0.01629638 Hz) and wide frequency bands. CPA tended to increase EEG power at low frequencies, and in several of the narrow frequency bands significantly shifted peak frequencies to lower values. The agonist also increased peak power in some frequency bands. The results are consistent with the view that A1 adenosine receptors mediate a generally depressant effect on neuronal activity in most brain regions, but may increase activity in areas with low resting rates of firing. The modest elevation of wave power by CPX indicates a limited control by resting endogenous adenosine, which is greatest in areas of highest activity, consistent with adenosine release being related to neuronal activity.

Experimental research on the effect of calcium channel blockers nifedipine and verapamil on the anxiety in mice.

The anxiolytic effect of the calcium channel blockers nifedipine and verapamil was tested in mice using two test: the conditioned suppression of the motility test and the black and white box test. The nifedipine but not the verapamil, in low doses (0.1 mg/kg b.w), proved anxiolytic effect and both nifedipine and verapamil in high dose (1.6-2.5 mg/kg b.w) had anxiogenic properties. The anxiogenic effect was correlated with the capacity of the drugs to block the calcium channels and the anxiolytic effect of low doses of the nifedipine was considered to be produced by opening these structures. These data were considered important for a new future aboard of the treatment and pathophysiology of the anxiety.

Effect of nifedipine on electrical activity of the brain in rat.

Effect of calcium channel blocker nifedipine on the electrical activity of the brain in anaesthetized rats was studied. The electoencephalographic signals were registered on a computer as series of data and thereafter they were decomposed by Fourier analysis in very narrow fields of frequency. The electrical activity of the brain of the control rats was asymmetrical, with a more important activity in the left brain hemisphere, particularly between 20-30 Hz when the electrical activity of the brain was globally more important. The nifedipine increased the electrical activity of the brain between 0.5-4 Hz and 20-30 Hz in a dose-dependent manner. The drug also increased the interhemispheric asymmetry. Some possible explanations of these effects are analyzed.

Effect of laser therapy on experimental inflammation in rats.

A favorable effect of laser therapy in rheumatic diseases was demonstrated in a previous paper [9] but it was not possible to estimate whether this benefit was due to an antiinflammatory, analgesic or decontracturant effect. In this work the effect of laser therapy was tested on an experimental inflammation in rats. Laser irradiation reduced the volume of the inflammation during 6 days of treatment more than 85% and prevented the appearance of necrosis. In the control group, the reduction of inflammation was of only 22.86%, the difference vs. the treated group being significant for p = 0.00009, and eight rats of the ten developed local necrosis.