Novel protective properties of auranofin: inhibition of human astrocyte cytotoxic secretions and direct neuroprotection.

AIMS: Steroidal and non-steroidal anti-inflammatory drugs are used for treatment of peripheral inflammation, but they are not effective in neurodegenerative disorders. Gold compounds are also used to treat peripheral inflammation, but their effects on neuroimmune reactions are unknown. This study investigated the effects of gold compounds on astrocytic cell functions and assessed in vivo distribution of auranofin after its oral administration in mice. MAIN METHODS: Auranofin and three other gold compounds were investigated for their ability to reduce the secretion of pro-inflammatory cytokines and cytotoxins produced by activated human astrocytic cells. Ability of the gold compounds to protect neuronal cells from glial cytotoxins and from oxidative damage induced by hydrogen peroxide was also studied. The in vivo distribution of auranofin was investigated using laser ablation inductively coupled plasma mass spectrometry (LA-ICP-MS). KEY FINDINGS: Auranofin (0.1-5 µM) inhibited the toxicity of stimulated primary human astrocytes and U-373 MG astrocytic cells towards human neuronal cells, but did not inhibit secretion of cytokines. Treatment of neuronal cells with high nanomolar to low micromolar concentrations of auranofin protected them from toxicity induced by hydrogen peroxide and supernatants of stimulated astrocytic cells through the upregulation of heme-oxygenase (HOX)-1. Aurothiomalate, aurothioglucose, and aurothiosulphate were ineffective in the assays used. Auranofin reached low micromolar concentrations in mouse brains following daily oral administration for one week. SIGNIFICANCE: Since auranofin may protect neurons by inhibiting astrocyte toxicity and is also directly neuroprotective, it could be useful in neurodegenerative diseases where activation of astrocytes contributes to the neuronal loss.

The biological activity of auranofin: implications for novel treatment of diseases.

More than 30 years ago, auranofin was developed for the treatment of rheumatoid arthritis as a substitution for the injectable gold compounds aurothiomalate and aurothioglucose. Both the ease of oral administration over intramuscular injections and more potent anti-inflammatory effects in vitro made auranofin seem like an excellent substitute for the traditional injectable gold compounds. Despite efficacy in the treatment of both rheumatoid arthritis and psoriasis, currently, auranofin is seldom used as a treatment for patients with rheumatoid arthritis as more novel anti-rheumatic medications have become available. Despite the decline in its clinical applications, research on auranofin has continued as it shows promise in the treatment of several different diseases. In recent years, advances in technology have allowed researchers to use molecular techniques to identify novel mechanisms of action of auranofin. Additionally, researchers are discovering potential new applications of auranofin. Dual inhibition of inflammatory pathways and thiol redox enzymes by auranofin makes it a new candidate for cancer therapy and treating microbial infections. This review will summarize recently obtained data on the mechanisms of action of auranofin, and potential new applications of auranofin in the treatment of various diseases, including several types of leukaemia, carcinomas, and parasitic, bacterial, and viral infections.

Spatio-temporal analysis of cyprinid herpesvirus 3 genetic diversity at a local scale.

Cyprinid herpesvirus 3 (CyHV-3), the causative agent of koi herpesvirus disease, is a major threat for carp populations in many countries worldwide, including Indonesia. It has been shown that many genotypes circulate worldwide, all highly related to one of the two known lineages U/I and J. In this study, we evaluated the spatial and temporal distribution of CyHV-3 strains in a small enzootic area, the lake of Cirata (West Java, Indonesia). Of the 365 samples analysed, from clinical or asymptomatic fish, 244 were found positive for CyHV-3, suggesting a high occurrence of the virus. Genotyping of these viral specimens with a range of molecular markers revealed the presence of numerous haplotypes in the host population, all related to the J lineage. In single individuals, mixed-genotype infections occurred at high frequency. The present results demonstrate that polymorphic molecular markers are suitable to monitor the genetic evolution of a viral population in an enzootic area.

Reduction of aflatoxin B1 in stored peanuts (Arachis hypogaea L.) using Saccharomyces cerevisiae.

Aflatoxin B(1) is a toxigenic and carcinogenic compound produced by Aspergillus flavus and Aspergillus parasiticus. To inhibit aflatoxin contamination of peanuts, seeds of two peanut breeds, IAC Caiapó and IAC Runner 886, were inoculated with A. parasiticus (1.0 × 10(6) spores per ml) and the yeast Saccharomyces cerevisiae (3.2 × 10(7) cells per ml) and incubated at 25°C for 7 and 15 days. Two experiments were conducted for each incubation period separately. The treatments were completely randomized, with three replications per treatment. Treatments included the two cultivars and three types of inoculation (pathogen alone, yeast and pathogen, and yeast 3 h before pathogen). Aflatoxin B(1) was quantified with a densitometer at 366 nm after thin layer chromatography. Aflatoxin B(1) contamination in peanuts was reduced after the addition of S. cerevisiae. The concentration of aflatoxin B(1) decreased by 74.4 and 55.9% after 7 and 15 days, respectively. The greatest aflatoxin reduction was observed when S. cerevisiae was inoculated 3 h before the pathogen in IAC Caiapó seeds and incubated for 7 days at 25°C. The use of S. cerevisiae is a promising strategy for biological control of aflatoxin contamination in peanuts.

Integrating user studies into computer graphics-related courses.

This paper presents computer graphics. Computer graphics and visualization are essentially about producing images for a target audience, be it the millions watching a new CG-animated movie or the small group of researchers trying to gain insight into the large amount of numerical data resulting from a scientific experiment. To ascertain the final images' effectiveness for their intended audience or the designed visualizations' accuracy and expressiveness, formal user studies are often essential. In human-computer interaction (HCI), such user studies play a similar fundamental role in evaluating the usability and applicability of interaction methods and metaphors for the various devices and software systems we use.

MRSA outbreak at a transplantation unit.

Methicillin-resistant Staphylococcus aureus (MRSA) infections frequently complicate the post-operative course of transplant recipients, and despite nasal carriage and endemic colonization, MRSA outbreaks are not commonly described. This study reports a case of MRSA outbreak and discusses infection control measures and recommendations for this situation.

Atrial flutter ablation with a new radiofrequency catheter.

OBJECTIVE: To assess the performance of a new radiofrequency catheter, specially designed for inferior vena cava-tricuspid annulus (IVC-TA) isthmus ablation, in the treatment of atrial flutter. PATIENTS: IVC-TA isthmus ablation was performed in thirteen patients, eleven men and two women, aged 60 +/- 12, with a diagnosis of typical atrial flutter, symptomatic despite anti-arrhythmic therapy. The flutter was present for more than one year in seven patients and was paroxysmal in the remainder. The echocardiogram showed atrial enlargement in six patients. Atrial flutter was an isolated phenomenon in seven patients and in the remainder was associated with arterial hypertension (two patients), ischemic heart disease (two patients) and dilated cardiomyopathy (two patients). METHODS: In the electrophysiologic study four diagnostic catheters were used, including one duodecapolar for mapping the tricuspid annulus. In the patients who presented with sinus rhythm, atrial flutter was induced with programmed atrial stimulation, and then the atrial activation circuit was mapped. To demonstrate the entrainment phenomenon the IVC-TA isthmus was over-stimulated, to prove that this was the slow zone of the circuit. The radiofrequency energy was applied in the IVC-TA isthmus with the Medtronic Cosio-Fluttr ablation catheter, for 60 sec per application, with temperature control and with a maximum energy output of 50 W. Criteria for success were not only the disappearance of the atrial flutter during the application of radiofrequency energy, but also the demonstration of bi-directional IVC-TA isthmus block. RESULTS: The primary success rate was 100%. The mean procedure time was 110 +/- 22 min, mean fluoroscopy time was 23 +/- 4 min and the number of radiofrequency energy pulses was 9 +/- 3. There were no complications. The patients were followed for a mean time of 8 +/- 4 months and atrial flutter recurred in only one patient (8%). CONCLUSIONS: Atrial flutter ablation with the new Medtronic Cosio-Fluttr catheter, specially designed for the application of radiofrequency at the IVC-TA isthmus, is a safe procedure and has a high success rate. It simplifies ablation, decreasing the number of radiofrequency energy pulses, without using long sheaths and keeping short procedure and fluoroscopy times.

[Deciding about pacing mode in sinus node dysfunction: should carotid sinus massage be performed and in which circumstances?]. / Decisão do modo de pacing na doença do nódulo sinusal: será a massagem do seio carotídeo pertinente e em que circunstâncias?

OBJECTIVE: To state the incidence of carotid sinus syndrome (CSS) with atrioventricular node manifestation in patients with sinus node dysfunction (SND) and indication for a definitive pacemaker (PM), we propose a new protocol between atrial pacing AAI and double chamber DDD. POPULATION AND METHODS: 69 patients (PTS) (male 71%), median age 65 +/- 10 years, with SND (normal PQ and no intraventricular conduction defect), that had a PM implant following the protocol that included carotid sinus massage for the pacing decision, were followed prospectively between December 1995 and November 1999. During the protocol we implanted DDD PM in PTS with Wenckebach less than 130 or Wenckebach equal/over 130 and CSS. At least, in PTS with Wenckebach equal/over 130 and no CSS we implanted AAI PM. The follow-up was between 4 months and 4 years, with clinical evaluation in the first and fourth months and then half yearly, with carotid sinus massage in the first evaluation. RESULTS: About 1/4 of the 69 patients followed had SND without carotid sinus syndrome, or atrioventricular node repercussion; the SND involved the atrioventricular node in 56% of the patients, and there was a relation between the SND and carotid sinus syndrome in 18.8%. The follow-up revealed, in all patients, a complete remission of the symptoms, and when we repeated the carotid sinus massage in the first evaluation, there was a response like in the surgery room, in all patients. CONCLUSIONS: There is a significant number of patients with SND and carotid sinus syndrome. The carotid sinus massage performed in the surgery room does not influence the test sensitivity and specificity in the diagnosis of carotid sinus syndrome. The authors think that carotid sinus massage should be considered in the protocol that defines the pacing mode, in patients with SND, and that influence the choice of pacemaker in 18.8% of patients.

Selection of homogeneous populations for genetic study: the Portugal genetics of psychosis project.

Molecular genetic studies of psychiatric disorders must face the possibility that despite the significant contribution of genetic factors to the expression of syndromes like schizophrenia, these syndromes may be a heterogeneous collection of genetic and non-genetic illnesses. These illnesses may be etiologically distinct from each other and still share many clinical features in common. Linkage studies of families with multiple affected members tend to favor the selection of genetic forms of a syndrome but can still represent a heterogeneous set of different genetic illnesses. To limit the potential genetic heterogeneity of a study sample, we selected a population that was geographically isolated and was historically relatively genetically homogeneous. We then assessed the relative level of homogeneity utilizing a surname analysis of the population of the Azores, mainland Portugal, rural USA, and urban USA. The average number of families with the same last name corrected for population size in the Azores is 30.88, in Coimbra it is 21.42, compared to 1.13 in a rural American population and 0.38 in an urban American population. The results of this analysis indicate that the Azores have the highest degree of homogeneity, and mainland Portugal has a high degree of homogeneity.

[Special issue in honor of Joao Lyra Madeira].

PIP: This issue contains a selection of papers by the late Joao L. Madeira which have been previously published in the Revista Brasileira de Estatistica, together with an obituary and an annotated bibliography of his works.^ieng

[Population dynamics and relation with the middle class]. / Dinamica populacional e suas relacoes com o meio ambiente.

PIP: It has been estimated that 200,000 years before the Christian era there were about 5 million people; at the beginning of the Christian era there were probably about 200-300 million people, which means a growth rate of roughly 0.0006/1000 during that period. Today, with a population of about 4 billion, the growth rate is estimated to be 20/1000. If this rate of growth continues for the next 1000 years, we would have, at the end of that period, a population density of 20,000 inhabitants per square meter, which is obviously absurd since it would be impossible to live under such conditions. Some factors are necessary for human life, and nonhuman life: food, space, and favorable conditions. It seems that men are doing their utmost to negatively modify these conditions; food is already getting scarce because of pollution of sea and land, and because of deforestation; space will become scarce because of the number of people and the incredible spreading of cities; conditions of life, especially emotional ones, will be affected by the first 2 factors, by the widespread search for superfluous goods, and by energy consumption. Family planning must be one of the first duties of mankind; it must be taught in schools as part of the regular education of young people; young couples must have free and easy access to family planning centers and the most modern contraceptive methods. It may be already too late, for some countries, to correct the far ranging implications of a high fertility rate; for Brazil it may still be possible to redress the situation, and provide a more dignified way of life for generations to come.^ieng

Epidural mastoid pneumatocele.

The authors report a case of a gas-filled epidural cyst communicating with the mastoid air cells, causing fluctuating but progressive amaurosis. No prior report of a similar finding could be found in the literature.

[Towards a demographic policy].

PIP: A demographic policy is an organic and integrated set of procedures designed to influence population growth and movement directly and indirectly in accordance with predetermined objectives. Such policy can affect age-sex distribution, marital patterns, health, and the geographical distribution of people within a country. Demographic policy must be an integral art of social welfare policy, of which socioeconomic development is 1 of the most important aspects. 2 points are considered to be most important in demographic research in Brazil; i.e., geographic distribution and population increase. Family size, both ideal and realized, and factors entering into decisions on family size are discussed as a primary component of population increase. Cost of children to poor and rich communities is contrasted. 6 stages of demographic research are discussed: 1) study of available material, 2) selection of goals, 3) preview of long- and short-term results, 4) comparison of results with the set goals, 5) establishment of corrective action, and 6) investigation of political action variables.^ieng

[Elements of analysis of the demographic processes in the Northeast (Brazil].

PIP: Demographic trends in Northeast Brazil over the last 100 years are presented and analyzed. The most important finding is a constant decline in the population of the Northeast relative to the rest of the country (46.70% of the population of Brazil lived in the Northeast in 1872, 30.34% in 1970; the population growth rates in 1872 and 1960 were 1.41 and 2.49% for the Northeast and 2.50 and 3.09% for the rest of the country). This trend appears to be continuing and, in the absence of concious policy decisions to the contrary, there will be further depopulation of the Northeast before a situation of equilibrium is reached, with a uniform growth rate for the entire country. The inaccuracies found in the older census data and the lack of some demographic statistics in the present records are discussed and measures are suggested to improve data collection, in order to provide a sound basis for demographic policy. Population changes resulting from migration and differential natural growth, and the direct and indirect contributions of migration from the Northeast to the rest of the country, are analyzed. The trend toward urbanization is also discussed: a smaller percentage of the population lives in cities of 20,000 or more in the Northeast than in the rest of the country, but recently that percentage has been growing at a faster rate.^ieng