The protective effect of extra-virgin olive oil in the experimental model of multiple sclerosis in the rat.

This study has evaluated the effect of EVOO (Extra-Virgin olive oil), OA (oleic acid) and HT (hydroxytyrosol) in an induced model of MS through experimental autoimmune encephalomyelitis (EAE).Dark Agouti 2-month old rats (25 males) were divided into five groups: (i) control group, (ii) EAE group, (iii) EAE+EVOO, (iv) EAE+HT, and (v) EAE+OA. At 65 days, the animals were sacrificed and the glutathione redox system and bacterial lipopolysaccharide (LPS) and LPS-binding protein (LBP) products of the microbiota in brain, spinal cord, and blood were evaluated.Gastric administration of EVOO, OA, and HT reduced the degree of lipid and protein oxidation, and increased glutathione peroxidase, making it a diet-based mechanism for enhancing protection against oxidative damage. In addition, it reduced the levels of LPS and LBP, which appeared as being increased in the EAE correlated with the oxidative stress produced by the disease.

Demonstration of Single-Barium-Ion Sensitivity for Neutrinoless Double-Beta Decay Using Single-Molecule Fluorescence Imaging.

A new method to tag the barium daughter in the double-beta decay of ^{136}Xe is reported. Using the technique of single molecule fluorescent imaging (SMFI), individual barium dication (Ba^{++}) resolution at a transparent scanning surface is demonstrated. A single-step photobleach confirms the single ion interpretation. Individual ions are localized with superresolution (∼2 nm), and detected with a statistical significance of 12.9σ over backgrounds. This lays the foundation for a new and potentially background-free neutrinoless double-beta decay technology, based on SMFI coupled to high pressure xenon gas time projection chambers.

Glycemic index, glycemic load, and pulse wave reflection in adults.

BACKGROUND AND AIMS: Diets with a high glycemic index (GI), high glycemic load (GL), or both, increase the risk of cardiovascular disease. This study examined the association of GI and GL in a regular diet with the peripheral augmentation index (i.e., a marker of vascular aging) in a sample of adults. METHODS AND RESULTS: Cross-sectional study. The findings presented in this manuscript are a subanalysis of the EVIDENT study whose purpose was to analyze the relationship between lifestyle and arterial aging. For the sample population, 1553 individuals aged 20-80 years were selected through random sampling from the patients of general practitioners at six health centers in Spain. GI and GL for each patient's diet were calculated from a previously validated, semi-quantitative, 137-item food frequency questionnaire. The peripheral augmentation index corrected for a heart rate of 75 bpm (PAIx75) was measured with pulse-wave application software (A-Pulse CASP). Based on a risk factor adjusted regression model, for every 5 unit increase in GI, the PAIx75 increased by 0.11 units (95% CI: 0.04-0.19). Similarly, for every increase in 10 units in GL, the PAIx75 increased by 1.13 (95% CI: 0.21-2.05). High PAIx75 values were observed in individuals with diets in the third GI tertile (i.e., the highest), and lower PAIx75 values in those with diets in the first tertile (i.e., the lowest), (93.1 vs. 87.5, respectively, p = 0.001). CONCLUSIONS: GI and GL were directly associated with PAIx75 values in adults without cardiovascular diseases regardless of age, gender, physical activity, and other confounders.

Demonstration of event position reconstruction based on diffusion in the NEXT-white detector.

Noble element time projection chambers are a leading technology for rare event detection in physics, such as for dark matter and neutrinoless double beta decay searches. Time projection chambers typically assign event position in the drift direction using the relative timing of prompt scintillation and delayed charge collection signals, allowing for reconstruction of an absolute position in the drift direction. In this paper, alternate methods for assigning event drift distance via quantification of electron diffusion in a pure high pressure xenon gas time projection chamber are explored. Data from the NEXT-White detector demonstrate the ability to achieve good position assignment accuracy for both high- and low-energy events. Using point-like energy deposits from 83mKr calibration electron captures (E∼45 keV), the position of origin of low-energy events is determined to 2 cm precision with bias <1mm. A convolutional neural network approach is then used to quantify diffusion for longer tracks (E≥1.5 MeV), from radiogenic electrons, yielding a precision of 3 cm on the event barycenter. The precision achieved with these methods indicates the feasibility energy calibrations of better than 1% FWHM at Qßß in pure xenon, as well as the potential for event fiducialization in large future detectors using an alternate method that does not rely on primary scintillation.

Achievement of long-term lipid targets in a cohort of patients with acute coronary syndrome in real-world clinical practice.

INTRODUCTION AND OBJECTIVES: According to the recent European epidemiological studies, the degree of lipid control in patients with very high vascular risk is suboptimal. This study analyzes the epidemiological characteristics, cardiovascular risk factors, lipid profile, recurrence, and degree of achievement of long-term lipid targets, according to the ESC/EAS Guidelines, in a cohort of patients with acute coronary syndrome (ACS) in a real-world clinical practice setting. METHODS: This work is a retrospective cohort study of patients diagnosed with ACS admitted to the Coronary Unit of a tertiary hospital from January 1, 2012 to December 31, 2015 and followed-up on until March 2022. RESULTS: A total of 826 patients were studied. During the follow-up period, greater prescribing of combined lipid-lowering therapy was observed, mainly high- and moderate-intensity statins and ezetimibe. At 24 months after the ACS, 33.6% of living patients had LDL levels <70 mg/dl and 9.3% had LDL levels <55 mg/dl. At the end of the follow-up (101 [88-111] months), the corresponding figures were 54.5% and 21.1%. Some 22.1% of patients had a recurrent coronary event and only 24.6% achieved an LDL level <55 mg/dl. CONCLUSIONS: Achievement of the LDL targets recommended by the ESC/EAS guidelines is suboptimal in patients with ACS, both at two years and in the long-term (7-10 years), especially in patients with recurrent ACS.

[Analysis of the valproic acid-meropenem interaction in hospitalised patients]. / Análisis de la interacción ácido valproico-meropenem en pacientes hospitalizados.

INTRODUCTION: Published data demonstrate a serious interaction between valproic acid and meropenem. However, recommendations about the management of concomitant treatment are contradictory; some experts recommend closer monitoring of valproic acid serum concentrations and others recommend avoiding concurrent therapy. The purpose of this study is to critically analyse the interaction and to evaluate the impact of pharmaceutical intervention in the use of these drugs in hospitalised patients. MATERIAL AND METHODS: Study of the concomitant prescription of valproic acid and meropenem in a general hospital of 1,080 beds divided in to two periods; the first period was retrospective and observational and it was followed by a prospective period involving pharmaceutical intervention. The prescription habits between both periods were compared. RESULTS: A total of 26 patients received concurrent treatment with valproic acid and meropenem (13 per period) and none of them maintained therapeutic serum levels of the antiepileptic drug. Pharmaceutical intervention modified prescription habits, reducing by half the number of days of concomitant treatment, changing the antibiotherapy and/or monitoring serum concentrations more often. CONCLUSIONS: The interaction between valproic acid and meropenem is serious, especially because of the dramatic decrease in the antiepileptic serum concentrations. The concomitant use of both drugs should be avoided, replacing the antibiotherapy empirically, or according to the resistance profiles of the microorganism and maintaining the same the anti-epileptic treatment.

Update on the utility of en face optical coherence tomography in the assessment of vitreoretinal diseases.

En face optical coherence tomography (EF-OCT) is a rapid, non-invasive, high-resolution imaging technique that has evolved in recent years to be a routine examination for the assessment and follow-up of various vitreoretinal diseases. With the introduction of swept-source OCT (SS-OCT), which can achieve up to 100,000 A-scans per second and better-quality imaging of deeper structures using a longer wavelength (1050nm), EF-OCT reconstruction can produce high-resolution frontal images of the retina and choroid (C-Scans) that give an overview of disease extent. These images allow a more accurate study of vitreoretinal interface pathologies such as epiretinal membranes, macular holes, and vitreomacular traction. They also provide key information in the study of various retinal vascular diseases and the differential diagnosis of cystic macular edema. EF-OCT provides valuable information about the severity of vitreoretinal interface alterations and precisely assesses the choriocapillaris and choroidal vasculature in pachychoroid disorders. Finally, this technique provides valuable information about atrophic and neovascular age-related macular degeneration and various uveitic entities. This review aims to describe the current clinical applications of EF-OCT in various vitreoretinal diseases as well as the latest findings and future perspectives.

Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Polymorphisms in cytochromes P450 2C8 and 3A5 are associated with paclitaxel neurotoxicity.

Neurotoxicity is one of the most relevant dose-limiting toxicities of the anticancer drug paclitaxel. It exhibits substantial interindividual variability of unknown molecular basis, and represents one of the major challenges for the improvement of paclitaxel therapy. The extensive variability in paclitaxel clearance and metabolism lead us to investigate the association between polymorphisms in paclitaxel elimination pathway and neurotoxicity. We selected 13 relevant polymorphisms in genes encoding paclitaxel metabolizing enzymes (CYP2C8, CYP3A4 and CYP3A5) and transporters (organic anion transporting polypeptide (OATP) 1B1, OATP1B3 and P-glycoprotein) and genotyped them in 118 Spanish cancer patients treated with paclitaxel. After adjusting for age and treatment schedule, CYP2C8 Haplotype C and CYP3A5*3 were associated with protection (hazard ratio (HR) (per allele)=0.55; 95% confidence interval (CI)=0.34-0.89; P=0.014 and HR (per allele)=0.51; 95%CI=0.30-0.86; and P=0.012, respectively) and CYP2C8*3 with increased risk (HR (per allele)=1.72; 95%CI=1.05-2.82; and P=0.032). In each case, the allele causing increased paclitaxel metabolism was associated with increased neurotoxicity, suggesting an important role for metabolism and hydroxylated paclitaxel metabolites. We estimated the HR per paclitaxel-metabolism increasing allele carried across the three polymorphisms to be HR=1.64 (95% CI=1.26-2.14; P=0.0003). The results for P-glycoprotein were inconclusive, and no associations were observed for the other genes studied. The incorporation of this genetic data in treatment selection could help to reduce neurotoxicity events, thereby individualizing paclitaxel pharmacotherapy. These results warrant validation in independent series.

[Analysis of errors in manual versus electronic prescriptions in trauma patients]. / Análisis de errores de la prescripción manual comparados con la prescripción electrónica asistida en pacientes traumatológicos.

OBJECTIVE: To detect, quantify, and compare the medication error produced with manual versus electronically assisted prescription systems. METHODS: A descriptive, observational, prospective study in two traumatology hospitalisation units; one with manual prescriptions and the other with electronically assisted prescriptions. Prescription errors were determined. RESULTS: We analysed 1,536 lines of treatment (393 treatment forms) from 164 patients. With manual prescriptions, we detected errors in 19.54% of cases, compared to 9.4% in electronically assisted prescriptions. Omission errors were significantly lower with electronically assisted prescriptions, especially with drugs that act upon the central nervous system. CONCLUSIONS: Prescription error has decreased by 53% since computerising the prescription process. This is particularly useful for omission errors, as prescription is more complete. The decrease in error regarding drugs that act on the central nervous system stands out.

Experimental measurement of the mobilities of atomic and dimer Ar, Kr, and Xe ions in their parent gases.

A new experimental technique for measuring the mobilities of positive ions in their parent gases is presented. The technique was applied to the rare gases, Ar, Kr, and Xe, and, for pressures typically below 10 Torr, two different types of positive ions were observed. The reduced mobilities of these ions in their parent gases were measured as a function of E/N, the ratio of the electric field strength to the gas number density, at a temperature of 300±1 K. The results were compared with others available in the literature and the two ions were identified as being the atomic and the dimer rare gas ions. The results are in good agreement with those from other authors. Space charge and impurities effects are discussed.

Development of a microalgal PAM test method for Cu(II) in waters: comparison of using spectrofluorometry.

Test methods are needed to monitor Cu concentrations in reservoirs and water supplies. Dictyosphaerium chlorelloides (Chlorophyta) cells were immobilized in a silicate sol-gel and the toxic effects of Cu(II) were examined using different techniques: fluorescence measurements (using a spectrofluorometer with an optic fiber coupled to a flow cell or a 96-well-plate reader) or by Pulse Amplitude Modulation (PAM) parameters using a portable instrument and the pulse saturation method. Fm' and qN were the most sensitive indicator parameters when performing Cu analysis in water. D. chlorelloides PAM biosensor presented a detection limit of 0.6 mg l(-1) for Cu(II), within the limits to establish if Cu concentrations exceeded regulatory levels. Moreover, a 1.9 mg Cu l(-1) (30 microM) resistant strain of the D. chlorelloides microalgae was produced in order to obtain more selectivity on the metal determination.

[New technologies applied to the medication-dispensing process, error analysis and contributing factors]. / Nuevas tecnologías aplicadas al proceso de dispensación de medicamentos. Análisis de errores y factores contribuyentes.

OBJECTIVE: Calculate error prevalence occurred in different medication-dispensing systems, the stages of occurrence, and contributing factors. METHODOLOGY: Prospective observational study. The staging of the dispensing process were reviewed in five dispensing systems: Stock, Unitary-Dose dispensing systems (UDDS) without Computerized Prescription Order Entry (CPOE), CPOE-UDDS, Automated Dispensing Systems (ADS) without CPOE and CPOE-ADS. Dispensing errors were identified, together with the stages of occurrence of such errors and their contributing factors. RESULTS: 2,181 errors were detected among 54,169 opportunities of error. Error-rate: Stock, 10.7%; no-CPOE-UDDS, 3.7%, CPOE-UDDS, 2.2%, no-CPOE-ADS, 20.7%; CPOE-ADS, 2.9%. Most frequent stage when error occurs: Stock, preparation of order; no-CPOE-UDDS and CPOE-UDDS, filling of the unit dose cart; no-CPOE-ADS and CPOE-ADS, filling of the ADS. Most frequent error: Stock, no-CPOE-ADS and CPOE-ADS, omission; CPOE-UDDS, different amount of drug and no-CPOE-UDDS, extra medication. Contributing factor: Stock, CPOE-ADS and no-CPOE-ADS, stock out/supply problems; CPOE-UDDS, inexperienced personnel and deficient communication system between professionals; no-CPOE-UDDS, deficient communication system between professionals. CONCLUSIONS: Applying new technologies to the dispensing process has increased its safety, particularly, implementation of CPOE has enabled to reduce dispensing errors.

Tisseel® versus Hemopatch® for dural sealing in neurosurgery. A prospective study in a tertiary center.

BACKGROUND: Dural repair is a potential source of complications in neurosurgery. We make a comparison in pseudomeningocele and CSF leak incidence with the sealants Tisseel® and Hemopatch®. METHODS: We collected 147 patients from September 2017 to December 2018 in a prospective observational study. Inclusion criteria were adult patients with an intradural cranial or spinal surgery whose dura was closed with a fibrin sealant. Primary endpoints were the incidence of pseudo meningocele and CSF leak. Secondary endpoints were the surgical-site infection, epidural hematoma, and the influence of previous surgery. RESULTS: In 65 and 82 patients Tisseel® and Hemopatch® were used as sealants respectively. The incidence of CSF leak presented a significant statistical relation with the use of Tisseel® in a univariate and multivariate analysis. Infratentorial surgery presented a higher incidence of pseudomeningocele and CSF leak, but the approach used was not a significant factor in multivariate analysis. Patients who were operated previously had a higher risk present a postoperative complication. CONCLUSIONS: The incidence of pseudomeningocele and CSF leak was higher with Tisseel® compared with Hemopatch® with a statistic significant relation in case of CSF fistulae. The procedure done may be a confusion factor in our study. There was no report of adverse effects or a higher incidence of complications. However, it is recommended to plan randomized trials with larger samples to get stronger evidence.

Determination of benzimidazole fungicides in water samples by on-line MISPE-HPLC.

An analytical methodology based on an on-line sample enrichment of water samples by means of an imprinted polymer, and the separation of benzimidazole compounds within a C(18) column by ion-pair reversed-phase liquid chromatography, has been developed. The molecularly imprinted polymer has been synthesized by precipitation polymerization using thiabendazole as template molecule, methacrylic acid as functional monomer, and divinylbenzene as cross-linker. Initial experiments carried out by solid-phase extraction on cartridges demonstrated a clear imprint effect for thiabendazole, as well as the ability of the imprinted polymer to selectively rebind several benzimidazole compounds. The developed methodology has been applied to the quantification of thiabendazole, carbendazim, and benomyl in river, tap, and well water samples within a single analytical run at concentration levels below the legislated maximum concentration levels. In this sense, detection limits of 2.3-5.7 ng.L(-1) have been obtained for the analysis of benzimidazole fungicides in different water matrices. Recoveries obtained for the determination of benzimidazole fungicides in spiked samples ranged from 87% to 95%, with RSD below 5% in all cases.

Molecular characterisation of a common SDHB deletion in paraganglioma patients.

BACKGROUND: Hereditary susceptibility to familial paraganglioma syndromes is mainly due to mutations in one of six genes, including three of the four genes encoding the subunits of the mitochondrial succinate dehydrogenase complex II. Although prevalence, penetrance and clinical characteristics of patients carrying point mutations affecting the genes encoding succinate dehydrogenase have been well studied, little is known regarding these clinical features in patients with gross deletions. Recently, we found two unrelated Spanish families carrying the previously reported SDHB exon 1 deletion, and suggested that this chromosomal region could be a hotspot deletion area. METHODS: We present the molecular characterisation of this apparently prevalent mutation in three new families, and discuss whether this recurrent mutation is due either to the presence of a founder effect or to a hotspot. RESULTS: The breakpoint analysis showed that all Iberian Peninsular families described harbour the same exon 1 deletion, and that a different breakpoint junction segregates in an affected French pedigree. CONCLUSIONS: After haplotyping the SDHB region, we concluded that the deletion detected in Iberian Peninsular people is probably due to a founder effect. Regarding the clinical characteristics of patients with this alteration, it seems that the presence of gross deletions rather than point mutations is more likely related to abdominal presentations and younger age at onset. Moreover, we found for the first time a patient with neuroblastoma and a germline SDHB deletion, but it seems that this paediatric neoplasia in a pheochromocytoma family is not a key component of this disease.

[The role of the cognitive reserve in the cognitive recovery of patients who have suffered a severe addiction to substances]. / Papel de la reserva cognitiva en la recuperacion cognitiva de pacientes que han sufrido una adiccion grave a sustancias.

INTRODUCTION: Cognitive reserve has been shown to be a prognostic variable in cognitive recovery after brain damage. Few studies have addressed its role in the cognitive status after a sustained period of substance addiction. AIM: To analyse the modulating role of cognitive reserve in the relation between withdrawal time and the cognitive status of patients with severe substance addiction. PATIENTS AND METHODS: A total of 26 patients recovering from severe substance addiction were assessed using a neuropsychological assessment protocol and cognitive reserve questionnaires. Exploratory factor analysis is used to define the variables and linear regression analysis is employed to view the predictive relations. RESULTS: Three cognitive functioning factors are obtained: processing integrity, inhibitory control and verbal memory, as well as an overall reserve factor. In the regression models, predictive relations are found only in a model of a direct relation between withdrawal and verbal memory, and in a model of an independent relation between cognitive reserve and withdrawal time and verbal memory, but not in the modulation relationship or in other relations in the rest of the factors. CONCLUSION: The article discusses the role of the cognitive reserve as a mediator in the cognitive status of patients in a period of withdrawal after a serious addiction to substances. A relationship with memory is shown, but no modulation of the role of withdrawal time on that cognitive status is detected.

TITLE: Papel de la reserva cognitiva en la recuperacion cognitiva de pacientes que han sufrido una adiccion grave a sustancias.Introduccion. La reserva cognitiva resulta ser una variable de pronostico en la recuperacion cognitiva tras un daño cerebral. Pocos estudios han abordado su papel en el estado cognitivo tras un periodo sostenido de adiccion a sustancias. Objetivo. Analizar el papel modulador de la reserva cognitiva sobre la relacion entre el tiempo de abstinencia y el estado cognitivo de los pacientes con adiccion grave a sustancias. Pacientes y metodos. Se valora a un total de 26 pacientes en recuperacion tras una adiccion grave a sustancias con un protocolo de evaluacion neuropsicologica y cuestionarios de reserva cognitiva. Se emplea el analisis factorial exploratorio para conformar las variables y el analisis de regresion lineal para ver las relaciones predictivas. Resultados. Se obtienen tres factores de funcionamiento cognitivo: integridad de procesamiento, control inhibitorio y memoria verbal, asi como un factor global de reserva. En los modelos de regresion, solo se encuentran relaciones predictivas en un modelo de relacion directa entre la abstinencia y la memoria verbal, y en un modelo de relacion independiente entre la reserva cognitiva y el tiempo de abstinencia con la memoria verbal, pero no en la relacion de modulacion, ni en otras relaciones en el resto de los factores. Conclusion. Se debate el papel de la reserva cognitiva como mediadora en el estado cognitivo en los pacientes en periodo de abstinencia tras una adiccion grave a sustancias: muestra una relacion con la memoria, pero no una modulacion del papel del tiempo de abstinencia sobre ese estado cognitivo.

Poly(ADP-ribose) polymerase inhibition reduces tumor necrosis factor-induced inflammatory response in rheumatoid synovial fibroblasts.

OBJECTIVES: To investigate the effect of poly(ADP-ribose) polymerase (PARP) inhibition on the production of inflammatory mediators and proliferation in tumour necrosis factor (TNF)-stimulated fibroblast-like synoviocytes (FLS) from patients with rheumatoid arthritis (RA). METHODS: Cultured FLS from patients with RA were treated with two PARP inhibitors, 3,4-dihydro-5-[4-1(1-piperidinyl)buthoxy]-1(2H)-isoquinolinona (DPQ) or 4-amino-1,8-naphthalimida (ANI) before TNF stimulation. PARP-1 expression was also suppressed in RA FLS by small interfering RNA (siRNA) transfection. Expression and secretion of inflammatory mediators were analysed by quantitative polymerase chain reaction and by enzyme-linked immunosorbent assay, respectively. Proliferation of RA FLS was also determined. Mitogen-activated protein kinase (MAPK) activity was analysed by western blot assay and activator protein (AP)-1 and nuclear factor (NF)kappaB binding by electrophoretic mobility shift assay. RESULTS: We show, for the first time, that PARP inhibition either with specific inhibitors or by siRNA transfection significantly reduced TNF-induced cytokine and chemokine expression in FLS from patients with RA. PARP inhibitors also decreased TNF-induced RA FLS proliferation. PARP inhibition reduced TNF-induced JNK phosphorylation and AP-1 and NF kappaB binding activities were partially impaired by treatment with PARP inhibitors or by PARP-1 knockdown. CONCLUSION: PARP inhibition reduces the production of inflammatory mediators and the proliferation of RA FLS (in response to TNF), suggesting that PARP inhibitors could have therapeutic benefits in RA.

Cytochrome P450 3A5 is highly expressed in normal prostate cells but absent in prostate cancer.

Testosterone is essential for the growth and function of the luminal prostate cells, but it is also critical for the development of prostate cancer, which in the majority of the cases derives from luminal cells. Cytochrome P450 3A (CYP3A) enzymes hydroxylate testosterone and dehydroepiandrosterone to less active metabolites, which might be the basis for the association between CYP3A polymorphisms and prostate cancer. However, it is unknown whether the CYP3A enzymes are expressed at relevant levels in the prostate and which polymorphisms could affect this tissue-specific CYP3A activity. Thus, we measured CYP3A4, CYP3A5, CYP3A7, and CYP3A43 mRNA in 14 benign prostatic hyperplasias and ten matched non-tumoral/tumoral prostate samples. We found that CYP3A5 mRNA in non-tumoral prostate tissue was 10% of the average amount of liver samples, whereas the expression of the other CYP3A genes was much lower. Similarly to liver, CYP3A5*3 polymorphism decreased CYP3A5 mRNA content 13-fold. CYP3A5 protein was detected in non-tumoral prostate microsomes by western blot, and immunohistochemistry (IHC) localized CYP3A5 exclusively in the basolateral prostate cells. In contrast to the normal tissue, IHC and RT-PCR showed that tumoral tissue lacked CYP3A5 expression. In conclusion, prostate basolateral cells express high levels of CYP3A5 which dramatically decrease in tumoral tissue. This finding supports an endogenous function of CYP3A5 related to the metabolism of intra-prostatic androgens and cell growth, and that polymorphisms affecting CYP3A5 activity may result in altered prostate cancer risk and aggressiveness.