The eye: A window to the soul of the immune system.

The eye is considered as an immune privileged site, and with good reason. It has evolved a variety of molecular and cellular mechanisms that limit immune responses to preserve vision. For example, the cornea is mainly protected from autoimmunity by the lack of blood and lymphatic vessels, whereas the retina-blood barrier is maintained in an immunosuppressive state by the retinal pigment epithelium. However, there are several scenarios in which immune privilege is altered and the eye becomes susceptible to immune attack. In this review, we highlight the role of the immune system in two clinical conditions that affect the anterior and posterior segments of the eye: corneal transplantation and age-related macular degeneration. Interestingly, crosstalk between the innate and adaptive immune systems is critical in both acute and chronic inflammatory responses in the eye, with T cells playing a central role in combination with neutrophils and macrophages. In addition, we emphasize the advantage of using the eye as a model for in vivo longitudinal imaging of the immune system in action. Through this technique, it has been possible to identify functionally distinct intra-graft motility patterns of responding T cells, as well as the importance of chemokine signaling in situ for T cell activation. The detailed study of ocular autoimmunity could provide novel therapeutic strategies for blinding diseases while also providing more general information on acute versus chronic inflammation.

Physiologic versatility and growth flexibility as the main characteristics of a novel thermoacidophilic Acidianus strain isolated from Copahue geothermal area in Argentina.

A novel thermoacidophilic archaeal strain has been isolated from three geothermal acidic hot springs in Copahue, Argentina. One of the most striking characteristic of ALE1 isolate is its metabolic versatility. It grows on sulphur, tetrathionate, iron (II) and sucrose under aerobic conditions, but it can also develop under anaerobic conditions using iron (III) or sulphur as electron acceptors and sulphur or hydrogen as electron donors autotrophically. A temperature of 75 °C and a pH between 2.5 and 3.0 are strain ALE1 optimal growth conditions, but it is able to oxidise iron (II) even at pH 1.0. Cells are irregular cocci surrounded by a regularly arrayed glycoprotein layer (S-layer). Phylogenetic analysis shows that strain ALE1 belongs to the family Sulfolobaceae in the class Thermoprotei, within the phylum Crenarchaeota. Based on 16S rRNA gene sequence similarity on NCBI database, ALE1 does not have closely related relatives, neither in culture nor uncultured, which is more surprising. Its closest related species are strains of Acidianus hospitalis (91 % of sequence similarity), Acidianus infernus (90 %), Acidianus ambivalens (90 %) and Acidianus manzanensis (90 %). Its DNA base composition of 34.5 % mol C + G is higher than that reported for other Acidianus species. Considering physiological and phylogenetic characteristics of strain ALE1, we considered it to represent a novel species of the genus Acidianus (candidatus "Acidianus copahuensis"). The aim of this study is to physiologically characterise this novel archaea in order to understand its role in iron and sulphur geochemical cycles in the Copahue geothermal area and to evaluate its potential applications in bioleaching and biooxidation.

First prokaryotic biodiversity assessment using molecular techniques of an acidic river in Neuquén, Argentina.

Two acidic hot springs close to the crater of Copahue Volcano (Neuquén, Argentina) are the source of the Río Agrio. The river runs several kilometres before flowing into Caviahue Lake. Along the river, temperature, iron, other metal and proton concentrations decrease gradually with distance downstream. From the source to the lake and depending on the season, pH can rise from 1.0 (or even less) to about 4.0, while temperature values decrease from 70°C to 15°C. Water samples were taken from different stations on the river selected according to their physicochemical parameters. In order to assess prokaryotic biodiversity throughout the water column, different and complementary molecular biology techniques were used, mainly in situ hybridisation and 16S rRNA gene cloning and sequencing. All microorganisms found are typical of acidic environments. Sulphur-oxidizing bacteria like Acidithiobacillus thiooxidans and Acidithiobacillus albertensis were detected in every station. Moderately thermophile iron- and sulphur-oxidizing bacteria like members of Alicyclobacillus and Sulfobacillus genera were also ubiquitous. Strict iron-oxidizing bacteria like Leptospirillum and Ferrimicrobium were present at the source of the river, but disappeared downstream where iron concentrations were much lower. Iron-oxidizing, mesophilic Ferroplasma spp. were the main archaea found. The data presented in this work represent the first molecular assessment of this rare natural acidic environment.

[Outpatient treatment of deep vein thrombosis: comparative study with historical inpatients]. / Tratamiento ambulatorio de la trombosis venosa profunda: comparación con tratamiento en hospitalización de pacientes de un registro histórico.

BACKGROUND: Outpatient treatment of deep venous thrombosis (DVT) has been proposed as a safe and cost-saving process, either as a mixed pattern: as an inpatient for 1 to 3 days followed by outpatient treatment; or rarely as completely outpatient. PATIENTS AND METHODS: We evaluated two cohorts of consecutive patients diagnosed with DVT. Patients who received entirely outpatient treatment in the years 2003 and 2004, compared with historical patients treated as inpatients during the year 2002. Our aim was to evaluate safety and the days of stay saved because of outpatient treatment of DVT. RESULTS: A total of 293 patients entered the study (Inpatients, 109; outpatients, 184). Demographic and clinical characteristics of patients were similar. Mean time of anticoagulant therapy and follow up were also both similar in the two groups. Major haemorrhage rate was 8% (CI 95% 4-15) in patients treated in hospital and 3% (CI 95%1-6.57) [Relative Risk (RR) 0.38] in patients treated as outpatients. Complications of venous thromboembolic disease occurred in 4% (CI 95% 1.18-9.68) of hospitalised patients and 5% (CI 95% 2.41-9.37) (RR 1.25) of patients treated as outpatients. The death rate was 11% (CI 95% 6-18.8) in hospitalised patients and 4% (CI 95% 1.68-7.99) (RR 0.36) in patients treated as outpatients. We observed a reduction of hospitalisation in relation to the index-year of 72.5% for the year 2003 (CI 95% -0.08 to -0.04) and 79% for the year 2004 (CI 95% -0.08 to -0.05) (p<0.001). Overall, 844 days of unnecessary hospitalisation were saved. CONCLUSIONS: Complete outpatient treatment of DVT shows outcomes at least as safe as inpatient treatment, adding additional reductions in costs for the Health System.

Metal biorecovery and bioremediation: Whether or not thermophilic are better than mesophilic microorganisms.

Metal mobilization and immobilization catalyzed by microbial action are key processes in environmental biotechnology. Metal mobilization from ores, mining wastes, or solid residues can be used for recovering metals and/or remediating polluted environments; furthermore, immobilization reduces the migration of metals; cleans up effluents plus ground- and surface water; and, moreover, can help to concentrate and recover metals. Usually these processes provide certain advantages over traditional technologies such as more efficient economical and environmentally sustainable results. Since elevated temperatures typically increase chemical kinetics, it could be expected that bioprocesses should also be enhanced by replacing mesophiles with thermophiles or hyperthermophiles. Nevertheless, other issues like process stability, flexibility, and thermophile-versus-mesophile resistance to acidity and/or metal toxicity should be carefully considered. This review critically analyzes and compares thermophilic and mesophilic microbial performances in recent and selected representative examples of metal bioremediation and biorecovery.

Draft Genome Sequence of the Sulfate-Reducing Bacterium Desulfotomaculum copahuensis Strain CINDEFI1 Isolated from the Geothermal Copahue System, Neuquén, Argentina.

Desulfotomaculum copahuensis strain CINDEFI1 is a novel spore-forming sulfate-reducing bacterium isolated from the Copahue volcano area, Argentina. Here, we present its draft genome in which we found genes related with the anaerobic respiration of sulfur compounds similar to those present in the Copahue environment.

Thermophiles in the genomic era: Biodiversity, science, and applications.

Thermophiles and hyperthermophiles are present in various regions of the Earth, including volcanic environments, hot springs, mud pots, fumaroles, geysers, coastal thermal springs, and even deep-sea hydrothermal vents. They are also found in man-made environments, such as heated compost facilities, reactors, and spray dryers. Thermophiles, hyperthermophiles, and their bioproducts facilitate various industrial, agricultural, and medicinal applications and offer potential solutions to environmental damages and the demand for biofuels. Intensified efforts to sequence the entire genome of hyperthermophiles and thermophiles are increasing rapidly, as evidenced by the fact that over 120 complete genome sequences of the hyperthermophiles Aquificae, Thermotogae, Crenarchaeota, and Euryarchaeota are now available. In this review, we summarise the major current applications of thermophiles and thermozymes. In addition, emphasis is placed on recent progress in understanding the biodiversity, genomes, transcriptomes, metagenomes, and single-cell sequencing of thermophiles in the genomic era.

[Severe primary vesicoureteral reflux in infants. A follow-up of 203 cases]. / El reflujo vesicoureteral primario severo en el primer año de la vida. Revisión de 203 casos.

OBJECTIVE: The aim of our study is to analyze the clinic characteristics and evolution of the primary reflux in infants. METHODS: We studied retrospectively 203 infants in our hospital, diagnosed of severe primary renal reflux. Renal ecography and cyclic mictional cystography were practiced in all cases. DMSA was carried out in 181 patients. RESULTS: Renal reflux was unilateral in the 23% of the patients, and bilateral in the remaining cases; 72% of the renal reflux were grade IV and 28% grade V. The renal injuries affected to male infants and reflux grade V. The renal injury was focal (27%), global (44%) and atrophic (29%). The 79% of the patients had conservative treatment, while 21% had surgical treatment. 100% infants with surgical treatment and 94.2% infants with conservative treatment were recovered (Test of Kaplan-Meier). The 27% of patients developed one or several urinary infections, but progression of old renal injuries or formation of new ones, were exceptional (3 cases): While the time the study lasted none of the patients developed chronic renal failure nor arterial hypertension. CONCLUSIONS: 1) The fetal severe primary reflux of the patients was characterized by the following features: to be bilateral reflux, to affect mainly to male infants and to be associated in 33% of cases with a severe renal injury of congenital origin (renal displasia) most of them unilateral. 2) The natural evolution of the reflux goes to spontaneous recovery, so treatment must be conservative. 3) Some patients underwent urinary infections, but progression or formation of new renal injuries were inusual. None of the patients had terminal renal failure nor hypertension and 4) Risk patients would be male infants with bilateral injuries although these are infrequent.

[Incidence of typhoid fever in our environment. Analysis in Guipúzcoa]. / Incidencia de la fiebre tifoidea en nuestro medio. Análisis en Guipúzcoa.

Based in 184 cases of Typhoid Fever bacteriologically demonstrated in the past 14 years (greater than 90% of all cases registered in the whole province), we have observed that, with the exception of some epidemic outbreaks, the disease has been constantly present during all these years, with a higher incidence between August and November. Salmonella typhi infected primarily young adults, its distribution being similar to the one among the general population. 49% of cases were males. The estimated incidence rate of the disease during this period was 2-3 per 100,000 population. A seroepidemiological study among healthy women with ages between 20 and 40 years showed a seroprevalence of anti-H:d antibodies greater than or equal to 1/40 of 1%. Although the epidemiological situation of Typhoid fever in our environment is not as bad as it has been referred in reports and textbooks, an effort is needed to situate the problem at the appropriate level, given our geographical situation and our economical development.

[Cases of tetanus in Guipuzcoa]. / Casos de tétanos en Guipúzcoa.

In order to evaluate the situation of tetanus in Guipúzcoa and to assess the impact of preventive measures, we studied the incidence, mortality and other aspects of the disease during the past three decades. Ninety eight cases were detected (annual average 3,27 SD 2,6), this figure being reduced over time (7,2 cases per year during the period 1962-1966; 1,8 cases per year between 1987 and 1991). 67,3% were men and 32,7% women. We registered 6 cases of neonatal tetanus, all of them prior to 1976. Since 1969, there has been no cases within the 1-14 age group. Half of the cases detected during the last five years (4/9) were intravenously drug-addicts. Among those living in less populated areas (less than 10.000 population), the risk of developing the disease was four times greater. 33,7% of patients died, being the mortality rate higher among newborns and patients died, and patients over 55. Although the situation was not worse than in other similar environments, the incidence of tetanus should be reduced by reinforcing preventive measures.

Archaeal and bacterial diversity in five different hydrothermal ponds in the Copahue region in Argentina.

Copahue is an acidic geothermal volcanic region in the northwest corner of Neuquén Province, Argentina. In the area, there are various ponds, pools and hot springs with different temperatures, pH values and levels of anthropogenic influence. In this study, the prokaryotic biodiversity of five representative ponds was studied by using two complementary molecular ecology techniques: phylogenetic analysis of 16S rRNA bacterial and archaeal genes and FISH (or CARD-FISH) for quantitative estimation of biodiversity. The results, supported by multivariate statistical analysis, showed that the biodiversity in Copahue ponds seemed to be determined by temperature. High temperature ponds were dominated by archaea, mainly apparently novel representatives from the orders Sulfolobales and Thermoplasmatales that had no close cultivated relatives. By contrast, moderate temperature ponds were colonised by well-characterised sulphur-oxidising bacteria related to acidic environments, such as other geothermal sites or acid mine drainage, and archaea were absent. By combining the biodiversity results from this study and the reported physicochemical features of Copahue, a preliminary model of the possible biogeochemical interaction was outlined for moderate and high temperature ponds.

Draft Genome Sequence of the Novel Thermoacidophilic Archaeon Acidianus copahuensis Strain ALE1, Isolated from the Copahue Volcanic Area in Neuquen, Argentina.

Acidianus copahuensis is a recently characterized thermoacidophilic archaeon isolated from the Copahue volcanic area in Argentina. Here, we present its draft genome sequence, in which we found genes involved in key metabolic pathways for developing under Copahue's extreme environmental conditions, such as sulfur and iron oxidation, carbon fixation, and metal tolerance.

[Dabigatran as a therapeutic possibility in heparin-induced thrombocytopenia type II]. / Dabigatran como posibilidad terapéutica en el síndrome de trombocitopenia inducida por heparina tipo II.

The syndrome of heparin-induced thrombocytopenia (HIT), with an incidence of 0.2-0.5% in patients exposed to heparin for more than 4 days, is produced by an immune alteration with the formation of antibodies against the heparin platelet factor 4 complex. It presents a wide spectrum of clinical manifestations, the most frequent of which are thrombocytopenia, thrombotic arterial-venous phenomena, and cutaneous necrosis. Up to the present, lepiridin, recently suspended, and argatroban (direct thrombin inhibitors) have been the approved medicines normally used in treatment, administered in parenteral form. Dabigatran, a new anticoagulant medicine that is a direct and reversible thrombin inhibitor, could theoretically be a medicine employed in treating HIT. According to the bibliography consulted we are presenting the first case of HIT treated with dabigatran in the medical literature.

[Hormonal and inflammatory biomarkers in a group of overweight and obese women]. / Parámetros hormonales e inflamatorios en un grupo de mujeres con sobrepeso/obesidad.

BACKGROUND AND OBJECTIVES: The aim of this study was to describe the hormonal and inflammatory status of a group of overweight/obese women. PATIENTS AND METHODS: The sample studied was a crosssectional cohort of women > 18 years of age, BMI ≥ 25 < 40 kg/m², prior to starting a weight control program. Data collected were: demographic characteristics, blood pressure, anthropometric parameters, physical activity data, and biochemical, hormonal and inflammatory biomarkers. RESULTS: The study involved 104 women with a mean age of 48.4 ± 9 years and a BMI of 29.8 ± 3.5 kg/m². Some 48% of the women studied were in menopause. Some 8.9% had hyperinsulinemia. The mean ghrelin value was 38.8 ± 33.6 pg/ml; there was no correlation between ghrelin levels and anthropometric and biochemical variables. CRP, leptin, adiponectin, resistin, IL6, IL10, and PAI1 were 3.0 ± 2.7 mg/dl, 36.3 ± 19.5 ng/ml, 8.3 ± 4.5 mg/ml, 24.3 ± 23.2 ng/ml, 51.6 ± 93.6 pg/ml, 10.0 ± 34.2 pg/ml and 22.3 ± 30.6 ng/ml, respectively. Obese patients had significantly higher mean values of resistin and PAI 1 than those who were overweight. These levels correlated significantly with anthropometric and biochemical variables; however, the correlations were weak. Age, menopause or the regular practice of physical activity had no effect on mean values. CONCLUSIONS: The group of women studied had altered inflammatory biomarkers in relation to people of normal weight. The study shows the inflammatory status of overweight/ obese individuals, and the values obtained may help to establish standard ranges for these markers.

A prospective, observational study describing the haematological response in patients undergoing chemotherapy treated by tri-weekly darbepoetin alfa for anaemia.

OBJECTIVE: This prospective, observational study investigated the haematological response to darbepoetin alfa (DA) administered every three weeks for the treatment of anaemia. Response was also assessed according to baseline characteristics including iron, folate and vitamin B12 status. RESEARCH DESIGN AND METHODS: Anaemic adult patients with malignant non-myeloid cancer, starting or having already undergone chemotherapy received DA on day of inclusionand were followed up for up to 24 weeks. Concentration of haemoglobin (Hb), as well as iron, vitamin B12 and folate status where available, were recorded at inclusion, after a treatment period of 9 weeks and up to a maximum of 24 weeks or cessation of DA treatment, whichever was sooner. MAIN OUTCOME MEASURES: The main outcome measure assessed in this study was the percentage of patients reaching a Hb concentration of at least 11 g/dL at least once at any time during the study. RESULTS: A total of 2912 patients were included. The mean Hb concentration increased from 10.0 g/dL at inclusion to 11.4 g/dL at 9 weeks and 11.8 g/dL at 24 weeks. In 74.6% of patients the target Hb level of 11.0 g/dL or above was reached. After initiation of DA treatment, 9.5% of patients required a blood transfusion by week 9, and 5.6% thereafter. Vitamin B12 and folate status were unknown for 80.3% of patients and the iron status for 73.2% of patients. Compared with patients who remained untreated for vitamin B12 or folate deficiency, a higher percentage of patients with vitamin status within normal limits achieved the target Hb concentration. However, achievement of target Hb level appeared not to be affected by iron status. CONCLUSIONS: In this study, the mean Hb level increased in anaemic cancer patients treated with DA and the majority of patients achieved the target Hb level. In contrast to the recommendations of guidelines (EORTC) encouraging the measurement of iron and vitamin levels, the present study demonstrated that data were not routinely collected for these factors.

Falling incidence and prevalence of hepatitis A in northern Spain.

The prevalence of hepatitis A virus antibodies was studied using a commercial ELISA method. 2,214 subjects were included, 1,211 in 1992 and 1,003 during 1986-87. In 1992 the seroprevalence rates among subjects 1-9, 10-19, 20-29 and 30-39 years old were 2.4%, 21%, 57.6% and 87.5% respectively, as compared with 7.7%, 37.9%, 80.6% and 98.1% respectively, in a similar group of subjects studied 5 years earlier (p < or = 0.001). The reported number viral hepatitis cases declined from 35.0 per 100,000 people in 1984 to 8.9 per 100,000 in 1992. Concurrently, the age when contracting the disease rose. The mean age for patients acquiring hepatitis A was 15.5 in 1986-88 and 20.1 in 1991-92. The decline in incidence and prevalence of HAV infection indicates a progressive and continuous decrease in HAV circulation in this geographical area.

[Malaria. Experience at a general hospital]. / Paludismo. Experiencia en un hospital general.

General hospitals should not ignore tropical diseases, even if they are not directly concerned with them. In our area, 3 and 6 instances of malaria have been diagnosed per year, 13 cases having been observed during the last 3 years. Prognosis is related with the quickness in achieving the diagnosis after the onset of symptoms; in our series it ranged from 4 days and one month. The outcome was good in all cases. To keep a reasonable good suspicion level, it should be remembered that the latency period between the infection and the development of symptoms may be very long. In 4 patients, the symptoms began 6 or more months after the patient had returned from the endemic zone. Chemoprophylaxis does not prevent the development of the disease in all individuals, although it is an effective prophylactic measure. Eight of these 13 patients had not undergone chemoprophylaxis or it had been incorrect. There was a remarkably high rate of patients infected by Pl. falciparum strains with in vivo resistance to antimalarial agents (chloroquine and fansidar).

Neutralizing antibodies in 6-year-old children after five doses of tetanus toxoid.

It has recently been suggested that multiple boosters of tetanus toxoid may enhance serum antitoxin titres but may not necessarily lead to an effective immune response. Tetanus antitoxin titres by haemagglutination inhibition and mouse toxin neutralization tests were determined in sera of 64 children, 5 and 6 years old. Primary vaccination against tetanus was given as four doses of diphtheria-pertussis-tetanus (DPT) vaccine beginning in the second or third month of life, and a booster dose given to schoolchildren at 6 years of age. In our area more than 90% of children receive five doses of tetanus toxoid before their seventh birthday. The children were given 0.5 ml of DPT or DT containing 10 Lf ml-1 tetanus toxoid at each injection. The haemagglutination titres and the toxin neutralization titres were much higher in 6-year-old than in 5-year-old children. We concluded that the fifth dose is an effective booster in 6-year-old children.

Ten-year survey of quinolone resistance in Escherichia coli causing urinary tract infections.

In a ten-year survey (1983-1992) of quinolone resistance in Escherichia coli causing urinary tract infections in a general practice patient population, 9,934 strains were tested. Resistance increased remarkably from 1989 onwards. The rate of resistance to pipemidic acid was < or = 6% before 1989 and 18% in 1992; the rate of resistance to ciprofloxacin (MIC > or = 4 mg/l) was 0.8% in 1989 and 7.1% in 1992. Although the consumption of older quinolones decreased the total consumption of quinolones increased yearly.