Faecal contamination in public pools in Barcelona province: Cryptosporidium spp. and bacterial indicators.

A study was conducted of the occurrence of Cryptosporidium in indoor heated public swimming pools and of three bacterial indicators (Escherichia coli, faecal enterococci and Clostridium perfringens) on pool surrounds. Although all examined pools adhered strictly to the Spanish regulations, the influence of several parameters related to water conditions, pool structure, users and location on the presence of protozoa and bacteria was analysed. Cryptosporidium was detected in 18.8% of pools in 60% of the five towns studied. The maximum concentration was 13 oocysts/L in one swimming pool and one Jacuzzi. The bacterial indicators' prevalence on pool surrounds was higher than 50%, being present in all of the towns. Plastic surfaces presented the lowest bacterial prevalence, whereas painted surfaces were 100% positive. No differences were observed for pool surrounds with autonomous or disabled users. Risk of cryptosporidiosis in pool vessels indicated that concentrations over 1 oocyst/10 L enhance the risk of infection, even in one exposure. Guidelines for managing faecal accidents and public information on the importance of good hygiene behaviours in and around swimming pools are recommended to limit oocysts' presence.

Structure and interaction with lipid membrane models of Semliki Forest virus fusion peptide.

Semliki Forest virus (SFV) is a well-characterized alphavirus that infects cells via endocytosis and an acid-triggered fusion step using class II fusion proteins. Membrane fusion is mediated by the viral spike protein, a heterotrimer of two transmembrane subunits, E1 and E2, and a peripheral protein, E3. Sequence analysis of the E1 ectodomain of a number of alphaviruses demonstrated the presence of a highly conserved hydrophobic domain on the E1 ectodomain. This sequence was proposed to be the fusion peptide of SFV and is believed to be the domain of E1 that interacts with the target membrane and triggers fusion. Here, we investigate the structure and the interaction with lipid membrane models of 76YQCKVYTGVYPFMWGGAYCFC96 sequence from SFV, named SFV21, using optical method (ellipsometry) and vibrational spectroscopiy approaches (Polarization Modulation infra-Red Reflection Absorption Spectroscopy, PMIRRAS, and polarized ATR-FTIR). We demonstrate a structural flexibility of SFV21 sequence whether the lateral pressure and the lipid environment. In a lipid environment that mimics eukaryotic cell membranes, a conformational transition from an α-helix to a ß-sheet is induced in the presence of lipid by increasing the peptide to lipid ratio, which leads to important perturbations in the membrane organisation.

Prediction of the potential biological activity of novel spiropyrazolo[3,4-b]pyridines and spiropyrazolo[3,4-b]pyridine-5,5'-pyrimidines by a ligand-protein inverse-docking approach.

The interaction of a series of spiropyrazolo[3,4-b]pyridines and spiropyrazolo[3,4-b]pyridine-5,5'-pyrimidines with 975 molecular targets involved in different diseases and biochemical alterations in humans was assessed. In-silico and in-vivo methods were used to predict the potential biological activity of these compounds. The exposure of several individuals of C. elegans to these compounds shows that their lethality would be less than 10% and that they do not induce any alteration in their locomotion. The compounds identified as PRV-8 and 13-G were the most bioactive, and also showed other advantages such as; better structural properties, adequate pharmacokinetic and pharmacodynamic properties, and good flexibility and unsaturation, which placed them as the compounds of greatest interest to be tested in-vitro and in-vivo. The series of compounds described here exhibited significant interactions with the estrogen signaling pathway.

[Cognitive-behavioural group therapy for insomnia: evaluation of the results after its implementation in a health department]. / Terapia grupal cognitivo-conductual para el insomnio: evaluación de resultados tras su introducción en un departamento de salud.

INTRODUCTION: Cognitive-behavioural therapy (CBT) is the preferred treatment in cases of chronic insomnia disorder in adults. PATIENTS AND METHODS: Open pragmatic study of 32 patients after eight sessions of group CBT for insomnia. RESULTS: Remission (insomnia severity index: 0-7 points) and response (insomnia severity index drops to > 8) were 31.3% and 46.9% at one month (n = 32) and 42.8% and 52.4% at one year (n = 21), respectively, with an effect size of 1.9 at one month and 2.3 at one year. At one month, 40.6% met the criteria for a case of insomnia (according to the insomnia symptoms questionnaire), and at one year, 19%, with a significant improvement in the symptoms at night and the consequences during the day. The questions of the Pittsburgh Sleep Quality Index on insomnia and sleep efficiency also improved. The pre-sleep arousal scale (n = 7) showed a shift from significant somatic and cognitive arousal to no arousal at one month. In the sleep diaries, total sleep time increased by an average of 53 minutes at one month (n = 14) and 76 minutes at one year (n = 10), with an increase of more than 10% in 71.4% of patients at one month and at one year, and an average sleep efficiency of more than 85%. The effect size for total sleep time and sleep efficiency was between 0.7 and 1. CONCLUSIONS: Group CBT for insomnia appears to be an effective treatment option in a clinical setting.

TITLE: Terapia grupal cognitivo-conductual para el insomnio: evaluación de resultados tras su introducción en un departamento de salud.Introducción. La terapia cognitivo-conductual (TCC) es el tratamiento de elección en el trastorno de insomnio crónico en adultos. Pacientes y métodos. Estudio pragmático abierto de 32 pacientes tras ocho sesiones de TCC grupal para el insomnio. Resultados. La remisión (índice de gravedad del insomnio: 0-7 puntos) y la respuesta (caída del índice de gravedad del insomnio > 8) fue del 31,3% y 46,9% al mes (n = 32) y del 42,8% y 52,4% al año (n = 21), respectivamente, con un tamaño del efecto de 1,9 al mes y 2,3 al año. Al mes, el 40,6% cumplía criterios de caso de insomnio (según el cuestionario de síntomas de insomnio), y al año, el 19%, con una mejoría significativa de síntomas nocturnos y consecuencias diurnas. También mejoraron las preguntas del índice de calidad de sueño de Pittsburgh sobre el insomnio y la eficiencia del sueño. La escala de activación previa al sueño (n = 7) mostró un trasvase desde activación significativa somática y cognitiva a ausencia de activación al mes. En los diarios de sueño, el tiempo total de sueño aumentó 53 minutos de media al mes (n = 14) y 76 al año (n = 10), con un aumento superior al 10% en el 71,4% de los pacientes al mes y al año, y una eficiencia del sueño media superior al 85%. El tamaño del efecto para el tiempo total de sueño y la eficiencia del sueño estuvo entre 0,7 y 1. Conclusiones. La TCC grupal para el insomnio parece una opción terapéutica eficaz en un entorno clínico.

Transcranial direct-current stimulation (tDCS) improves detection of simple bright stimuli by amblyopic Long Evans rats in the SLAG task and produces an increase of parvoalbumin labelled cells in visual cortices.

In this work visual functional improvement of amblyopic Long Evans rats treated with tDCS has been assessed using the "slow angled-descent forepaw grasping" (SLAG) test. This test is based on an innate response that does not requires any memory-learning component and has been used before for measuring visual function in rodents. The results obtained show that this procedure is useful to assess monocular but not binocular deficits, as controls and amblyopic animals showed significant differences during monocular but not during binocular assessment. On the other hand, parvoalbumin labelling was analysed in three areas of the visual cortex (V1M, V1B and V2L) before and after tDCS treatment. No changes in labelling were observed after monocular deprivation. However, tDCS treatment significantly improved vision through the amblyopic eye, and a significant increase of parvoalbumin-positive cells was observed in the three areas, both in the stimulated hemisphere but also in the non-stimulated hemisphere. This effect occurred both in control and amblyopic animals. Thus, tDCS induced changes are similar in controls and amblyopic animals, although only the last one showed a functional improvement.

tDCS recovers depth perception in adult amblyopic rats and reorganizes visual cortex activity.

Amblyopia or lazy eye is a neurodevelopmental disorder that arises during the infancy and is caused by the interruption of binocular sensory activity before maturation of the nervous system. This impairment causes long-term deterioration of visual skills, particularly visual acuity and depth perception. Although visual function recovery has been supposed to be decreased with age as consequence of reduced neuronal plasticity, recent studies have shown that it is possible to promote plasticity and neurorestoration in the adult brain. Thus, transcranial direct current stimulation (tDCS) has been shown effective to treat amblyopia in the adulthood. In the present work we used postnatal monocular deprivation in Long Evans rats as an experimental model of amblyopia and the cliff test task to assess depth perception. Functional brain imaging PET was used to assess the effect of tDCS on cortical and subcortical activity. Visually deprived animals ability to perceive depth in the cliff test was significantly reduced in comparison to their controls. However, after 8 sessions of tDCS applied through 8 consecutive days, depth perception of amblyopic treated animals improved reaching control level. PET data showed 18F-FDG uptake asymmetries in the visual cortex of amblyopic animals, which disappeared after tDCS treatment. The possibility of cortical reorganization and stereoscopy recovery following brain stimulation points at tDCS as a useful strategy for treating amblyopia in adulthood. Furthermore, monocular deprivation in Long Evans rats is a valuable research model to study visual cortex mechanisms involved in depth perception and neural restoration after brain stimulation.

Effects of policosanol in the functional recovery of non-cardioembolic ischemic stroke hypertensive patients. / Efectos del policosanol en la recuperacion funcional de pacientes hipertensos con ictus isquemico no cardioembolico.

INTRODUCTION: Clinical studies results show that policosanol (20 mg/day) + aspirin therapy had benefits versus placebo + aspirin to patients with recent non-cardioembolic ischemic stroke. AIM: To analyze the policosanol treatment effects in the hypertensive patients included in two non-cardioembolic ischemic stroke recovery trials. PATIENTS AND METHODS: Hypertensive patients with a modified Rankin Scale (mRS) score 2 to 4 were randomized, within 30 days of onset, to policosanol + aspirin or placebo + aspirin, for six months. The primary outcome was mRS score reduction. RESULTS: One hundred forty two hypertensive patients (mean age: 66 years) were included in the analysis. Policosanol + aspirin decreased significantly the mRS score mean from the first interim check-up. The policosanol treatment effect did not wear off, on the contrary, even improved after six months therapy. More over, policosanol + aspirin (80.3%) treatment achieved significant results (mRS <= 1), whereas the placebo + aspirin did not (8.5%). Two patients discontinued and four (two from each group) referred mild adverse events. CONCLUSIONS: The treatment for six months with policosanol + aspirin in hypertensive patients who had suffered a non-cardioembolic ischemic stroke proved to be more effective than the placebo + aspirin treatment in the functional recovery of these patients.

TITLE: Efectos del policosanol en la recuperacion funcional de pacientes hipertensos con ictus isquemico no cardioembolico.Introduccion. Los resultados de los estudios clinicos muestran que el tratamiento con policosanol (20 mg/dia) + aspirina produce beneficios frente a placebo + aspirina en pacientes con ictus isquemico no cardioembolico reciente. Objetivo. Analizar los efectos del tratamiento con policosanol en pacientes hipertensos incluidos en dos ensayos de recuperacion de ictus isquemico no cardioembolico. Pacientes y metodos. Pacientes hipertensos que sufrieron un ictus en los 30 dias previos y que, con una puntuacion de 2 a 4 en la escala de Rankin modificada (mRS), se distribuyeron aleatoriamente en dos grupos y recibieron policosanol + aspirina o placebo + aspirina durante seis meses. La variable primaria de eficacia fue la reduccion de la puntuacion en la mRS. Resultados. Se incluyo a un total de 142 pacientes hipertensos (edad media: 66 años) en el analisis. El policosanol + aspirina disminuyo significativamente la puntuacion de la mRS desde el primer chequeo intermedio. El efecto del tratamiento con policosanol no desaparecio, sino que incluso mejoro despues de seis meses de tratamiento. El numero de pacientes que alcanzaron valores de la mRS <= 1 fue mayor en el grupo de policosanol + aspirina (80,3%) que en el de placebo + aspirina (8,5%). Dos pacientes causaron baja del estudio y cuatro (dos de cada grupo) refirieron efectos adversos leves. Conclusiones. El tratamiento durante seis meses con policosanol + aspirina a pacientes hipertensos que habian sufrido un ictus isquemico no cardioembolico demostro ser mas efectivo que el tratamiento con placebo + aspirina en su recuperacion funcional.

Impact on renal function of the use of sirolimus in cardiac transplantation.

INTRODUCTION: During the last few years sirolimus has been introduced as an alternative to preserve renal function in transplant recipients receiving calcineurin inhibitors. MATERIALS AND METHODS: We reviewed our results on the use of sirolimus in cardiac transplant recipients. RESULTS: Twenty-seven patients with an average age of 63 years received sirolimus. The average time after transplantation was 73.4 +/- 58.9 months and the average follow-up was 31.7 +/- 18.01 months. Sirolimus was prescribed in 37% of cases due to chronic renal failure (CRF), 14.8% because of cardiac allograft vasculopathy (CAV), 11.1% for tumors, 22.2% de novo, 7.4% for CRF and tumor, and 7.4% for CRF and CAV. Among the patients with CRF (n = 14), there were 5 (35%) on dialysis at the moment of starting the treatment and 1 was retired from dialysis. The other 4 (28.5%) patients had to be treated with dialysis after starting the treatment. In all, 42.8% of the patients with nephropathy maintained stable renal function or improved. Among the 17 (63%) patients who did not require dialysis, there was no significant change in renal function after 6 months or 1, 2, and 3 years follow-up. CONCLUSIONS: The use of sirolimus in cardiac transplantation maintains stable renal function in the majority of patients in the medium term.

The O3-Vet project: a veterinary electronic patient record based on the web technology and the ADT-IHE actor for veterinary hospitals.

A veterinary electronic patient record, compliant with the IT standards (HL7, DICOM and IHE), was developed at the School of Veterinary Medicine, University of Milan (Italy) in order to improve the veterinary hospital workflows, making the stored clinical data more homogenous and sharable, thereby increasing the integration with current and future software applications. The system was developed by open-source software in order to reduce the implementation and maintenance costs and to make the system sharable with other veterinary hospitals or research centers without additional costs. The system was tested from May to October 2006. Results show that the majority of the veterinarians involved in the test agreed on the advantages obtained by the use of application software concerning the availability of all the useful clinical data [71.4%], the quality of the diagnostic procedures [78.58%] and the efficiency [85.58%] of hospital activities.

[Basic principles of cardiovascular magnetic resonance (CMR): sequences, acquisition planes and study protocol]. / Principios básicos de resonancia magnética cardiovascular (RMC): secuencias, planos de adquisición y protocolo de estudio.

Evaluation of the cardiovascular system with magnetic resonance (CMR) has become one of the most relevant and up-to-the-minute clinical applications of this diagnostic technique, as CMR makes possible an exact and reproducible study of the anatomy and function of the heart and great vessels. The complexity of this technique is mainly due to the anatomical location and orientation of the cardiovascular structures, the specific CMR sequences that have to be used and a lack of familiarity amongst radiologists regarding cardiovascular pathology. In this report the most basic principles of CMR are described. The clinical usefulness of anatomical, functional, and flow quantification sequences are discussed, conventional CMR acquisition planes are described, and an easy CMR study protocol is proposed.

Transcranial direct current stimulation improves visual acuity in amblyopic Long-Evans rats.

Transcranial direct current stimulation (tDCS) has proved to increase brain cortex plasticity and different models of brain damage. In this work, we have analyzed the effects of tDCS in an experimental model of amblyopia using Long-Evans rats. Animals were monocularly deprived between 12 and 75 postnatal days and visual cortex contralateral to the deprived eye was stimulated using anodal tDCS during 8days (20min/day). The effects of tDCS treatment on the visual function were evaluated by using the optomotor reflex of the animals as a measure of visual acuity. Results obtained indicate that monocular occlusion during the critical period lead to a reduction of visual acuity in monocular and binocular conditions. Stimulation with anodal tDCS produced a nearly full recovery in visual acuity of amblyopic animals. However, same stimulation protocol in healthy control animals produced a decrease of binocular visual acuity. These data indicate that tDCS can reverse the effects of monocular deprivation on visual acuity, although it is essential to use this technique in a controlled way due to the possible adverse effects on healthy individuals.

Ideally amphipathic beta-sheeted peptides at interfaces: structure, orientation, affinities for lipids and hemolytic activity of (KL)(m)K peptides.

Designed to model ideally amphipathic beta-sheets, the minimalist linear (KL)(m)K peptides (m=4-7) were synthesized and proved to form stable films at the air/water interface, they insert into compressed dimyristoylphosphatidylcholine monolayers and interact with egg phosphatidylcholine vesicles. Whatever the interface or the lateral pressure applied to the films, FT-IR and polarization-modulated IRRAS spectroscopy developed in situ on the films indicated that all the peptides totally fold into intermolecular antiparallel beta-sheets. Calculated spectra of the amide region allowed us to define the orientation of the beta-strands compared to the interface. It is concluded that such beta-sheets remain flat-oriented without deep perturbation of zwitterionic phospholipids. Dansyl labelling at the N-terminus indicates that all the peptides are monomeric at a low concentration in aqueous buffer and bind to lipids with similar Dns burying. The affinities for zwitterionic lecithin mono- and bilayers, quantitatively estimated from buffer to lipid partition constants, monotonically increased with peptide length, indicating that hydrophobicity is a limiting parameter for lipid and membrane affinities. Peptides induced permeability increases on zwitterionic liposomes, they are strongly hemolytic towards human erythrocytes and their activity increases concurrently with length. Taking into account the lipid affinity, a hemolytic efficiency can be defined: at the same amount of peptide bound, this efficiency strongly increases with the peptide length. It is proposed that the first determinant step of membrane disturbance is the invasion of the outer membrane leaflet by these ideally amphipathic beta-sheeted structures lying flat at the interface, like large rafts depending on the number of beta-strands.

Structure, orientation and affinity for interfaces and lipids of ideally amphipathic lytic LiKj(i=2j) peptides.

The behavior of lytic ideally amphipathic peptides of generic composition LiKj(i=2j) and named LKn, n=i+j, is investigated in situ by the monolayer technique combined with the recently developed polarization modulation IR spectroscopy (PMIRRAS). A change in the secondary structure occurs versus peptide length. Peptides longer than 12 residues fold into alpha-helices at interfaces as expected from their design, while enough shorter peptides, from 9 down to 5 residues, form intermolecular antiparallel beta-sheets. Analysis of experimental and calculated PMIRRAS spectra in the amide I and II regions show that peptides are flat oriented at the interfaces. Structures and orientation are preserved whatever the nature of the interface, air/water or DMPC monolayer, and the lateral pressure. Peptide partition constants, KaffPi, are estimated from isobar surface increases of DMPC monolayers. They strongly increase when Pi decreases from 30 mN/m to 8 mN/m and they vary with peptide length with an optimum for 12 residues. This non-monotonous dependence fits with data obtained in bilayers and follows the hemolytic activity of the peptides. Lipid perturbations due to peptide insertion essentially detected on the PO4- and CO bands indicate disorder of the lipid head groups. Lysis induced on membranes by such peptides is proposed to first result from their flat asymmetric insertion.

The amphipathic helix concept: length effects on ideally amphipathic LiKj(i=2j) peptides to acquire optimal hemolytic activity.

In a minimalist approach to modeling lytic toxins, amphipathic peptides of LiKj with i=2j composition and whose length varies from 5 to 22 residues were studied for their ability to induce hemolysis and lipid vesicle leakage. Their sequences were designed to generate ideally amphipathic alpha helices with a single K residue per putative turn. All the peptides were lytic, their activities varying by more than a factor of 103 from the shortest 5-residue-long peptide (5-mer) to the longest 22-mer. However, there was no monotonous increase versus length. The 15-mer was as active as the 22-mer and even more than melittin which is used as standard. Partition coefficients from the buffer to the membrane increased in relation to length up to 12 residues, then weakly decreased to reach a plateau, while they were expected to increase monotonously with peptide length and hydrophobicity as revealed from HPLC retention times. Fluorescence labeling by a dansyl group at the N-terminus, or by a W near the CO-terminus, show that up to 12 residues, the peptides were essentially monomeric while longer peptides strongly aggregated in the solution. Lipid affinity was then controlled by peptide length and was found to be limited by folding and self-association in buffer. The lytic activity resulted both from lipid affinity, which varied by a factor of 20-fold, and from efficiency in disturbing the membrane when bound, the latter steeply and monotonously increasing with length. The 15-residue-long peptide, KLLKLLLKLLLKLLK, had the optimal size for highest lytic activity. The shallow location of the fluorescent labels in the lipids is further evidence for a model of peptides remaining flat at the interface.

[Heart failure. Current pharmacologic treatment]. / Insuficiencia cardiaca. tratamiento farmacológico actual.

Treatment of heart failure (HF) has changed in recent years, despite the paucity of new approved drugs. Current treatment is directed not only towards improving symptoms, but also to preventing the development from asymptomatic systolic dysfunction to symptomatic heart failure, to preventing cardiac remodelling, renal dysfunction and to reducing mortality. The main families of drugs currently used are: cardiac glycosides, diuretics, angiotensin-converting enzyme inhibitors (ACEI), beta-blocking drugs (BB), angiotensin-II receptor blockers (ARB) and aldosterone receptor antagonists. The combination isosorbide dinitrate + hydralazine is hardly used due to its side effects and none of the new positive inotropic drugs has been approved in chronic HF, because all of them increase mortality. Levosimendan is a new positive inotropic agent approved for acute HF by an intravenous route, with a favourable effect on prognosis vs placebo and vs dobutamine (which worsens the prognosis). The approved oral drugs can be given at the same time if the patient tolerates them, because their beneficial effect is additive. Mortality in two years in mild to moderate HF is 34% with glycosides + diuretics. It falls to 22% when an ACEI is added, to 14% when a BB is added and to 10% when an aldosterone antagonist is added. ARB can be given instead of an ACEI or be added to the other drugs.

[Post-infectious demyelinating diseases]. / Enfermedades desmielinizantes postinfecciosas.

Post-infectious demyelinating disorders are uncommon. In the Hospital Pediatrico de la Misericordia de Santafé de Bogotá there were 14 cases in three years. The commonest age group was the new born, as is found in the literature. The infections involved in these neurological changes are probably viral, since at the time the patient is seen most symptoms have cleared up spontaneously. According to several authors, the viruses are most often found to be those of measles or mumps. Between the infection and the development of neurological symptoms there is an interval of approximately two weeks. The main clinical findings are motor changes such as hemiparesis, involvement of cranial nerves and alterations of consciousness. The aetiology is not completely clear. Firm diagnosis is made on histopathological studies which are seldom available. Usually neuroimaging techniques and cerebrospinal fluid analysis are the basis of the diagnosis. Computerized axial tomography and magnetic resonance are the most useful noninvasive techniques for assessing the involvement of the white matter, the extent and sites of the lesions. It is useful to know the classification of the demyelinating disorders so as to prescribe, the most suitable treatment and give the prognosis in each case. There is still no specific treatment for these disorders. Supportive measures, the control of epileptic crises and the prevention of complications are the main aims. This paper reviews the definition, classification, diagnosis and management of these disorders.

Giant inguino-scrotal bladder hernia. Report of a case.

Bladder hernia is very uncommon. It tends to affect patients over the age of 50 and is predisposed by cervico-urethral obstruction. The condition is often diagnosed during inguinal hernia surgery. The authors report a case of massive inguino-scrotal bladder herniation. The different types of bladder hernia are described, and the clinical-radiological findings and surgical management are discussed.

Denitrification in a hypersaline lake-aquifer system (Pétrola Basin, Central Spain): the role of recent organic matter and Cretaceous organic rich sediments.

Agricultural regions in semi-arid to arid climates with associated saline wetlands are one of the most vulnerable environments to nitrate pollution. The Pétrola Basin was declared vulnerable to NO3(-) pollution by the Regional Government in 1998, and the hypersaline lake was classified as a heavily modified body of water. The study assessed groundwater NO3(-) through the use of multi-isotopic tracers (δ(15)N, δ(34)S, δ(13)C, δ(18)O) coupled to hydrochemistry in the aquifer connected to the eutrophic lake. Hydrogeologically, the basin shows two main flow components: regional groundwater flow from recharge areas (Zone 1) to the lake (Zone 2), and a density-driven flow from surface water to the underlying aquifer (Zone 3). In Zones 1 and 2, δ(15)NNO3 and δ(18)ONO3 suggest that NO3(-) from slightly volatilized ammonium synthetic fertilizers is only partially denitrified. The natural attenuation of NO3(-) can occur by heterotrophic reactions. However, autotrophic reactions cannot be ruled out. In Zone 3, the freshwater-saltwater interface (down to 12-16 m below the ground surface) is a reactive zone for NO3(-) attenuation. Tritium data suggest that the absence of NO3(-) in the deepest zones of the aquifer under the lake can be attributed to a regional groundwater flow with long residence time. In hypersaline lakes the geometry of the density-driven flow can play an important role in the transport of chemical species that can be related to denitrification processes.

Stra6, a retinoic acid-responsive gene, participates in p53-induced apoptosis after DNA damage.

Stra6 is the retinoic acid (RA)-inducible gene encoding the cellular receptor for holo-retinol binding protein. This transmembrane protein mediates the internalization of retinol, which then upregulates RA-responsive genes in target cells. Here, we show that Stra6 can be upregulated by DNA damage in a p53-dependent manner, and it has an important role in cell death responses. Stra6 expression induced significant amounts of apoptosis in normal and cancer cells, and it was also able to influence p53-mediated cell fate decisions by turning an initial arrest response into cell death. Moreover, inhibition of Stra6 severely compromised p53-induced apoptosis. We also found that Stra6 induced mitochondria depolarization and accumulation of reactive oxygen species, and that it was present not only at the cellular membrane but also in the cytosol. Finally, we show that these novel functions of Stra6 did not require downstream activation of RA signalling. Our results present a previously unknown link between the RA and p53 pathways and provide a rationale to use retinoids to upregulate Stra6, and thus enhance the tumour suppressor functions of p53. This may have implications for the role of vitamin A metabolites in cancer prevention and treatment.