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1. Impulsiveness as a timing disturbance: neurocognitive abnormalities in attention-deficit hyperactivity disorder during temporal processes and normalization with methylphenidate.

Rubia K, Halari R, Christakou A, Taylor E.

Department of Child Psychiatry/MRC Center for Social, Genetic and Developmental Psychiatry (SGDP), Institute of Psychiatry, 16 De Crespigny Park, London, UK. k.rubia@iop.kcl.ac.uk

We argue that impulsiveness is characterized by compromised timing functions such as premature motor timing, decreased tolerance to delays, poor temporal foresight and steeper temporal discounting. A model illustration for the association between impulsiveness and timing deficits is the impulsiveness disorder of attention-deficit hyperactivity disorder (ADHD). Children with ADHD have deficits in timing processes of several temporal domains and the neural substrates of these compromised timing functions are strikingly similar to the neuropathology of ADHD. We review our published and present novel functional magnetic resonance imaging data to demonstrate that ADHD children show dysfunctions in key timing regions of prefrontal, cingulate, striatal and cerebellar location during temporal processes of several time domains including time discrimination of milliseconds, motor timing to seconds and temporal discounting of longer time intervals. Given that impulsiveness, timing abnormalities and more specifically ADHD have been related to dopamine dysregulation, we tested for and demonstrated a normalization effect of all brain dysfunctions in ADHD children during time discrimination with the dopamine agonist and treatment of choice, methylphenidate. This review together with the new empirical findings demonstrates that neurocognitive dysfunctions in temporal processes are crucial to the impulsiveness disorder of ADHD and provides first evidence for normalization with a dopamine reuptake inhibitor.

PMID: 19487194 [PubMed - in process]

PMCID: PMC2685816 [Available on 2010/07/12]


2. Impact of hematopoietic chimerism at day +14 on engraftment after unrelated donor umbilical cord blood transplantation for hematologic malignancies.

Moscardó F, Sanz J, Senent L, Cantero S, de la Rubia J, Montesinos P, Planelles D, Lorenzo I, Cervera J, Palau J, Sanz MA, Sanz GF.

1Department of Hematology, Hospital Universitario La Fe, Valencia, Spain.

BACKGROUND: Cord blood transplant is a feasible treatment alternative for adult patients with hematologic malignancies lacking a suitable HLA-matched donor. However, the kinetics of myeloid recovery is slow, and primary graft failure cannot be detected easily early after transplantation. We investigated the impact of hematopoietic chimerism status from unselected marrow cells 14 days after transplantation on predicting engraftment after a cord blood transplant. DESIGN AND METHODS: Seventy-one adult patients with hematologic malignancies undergoing single-unit unrelated donor cord blood transplantation after a myeloablative conditioning regimen were included in the study. All patients received conditioning regimens based on busulfan, thiotepa and antithymocyte globulin. Chimerism status was assessed analyzing short tandem repeat polymorphisms. RESULTS: The cumulative incidence of myeloid engraftment at 1 month was significantly lower in patients with mixed chimerism than in those with complete donor chimerism (55% vs. 94%; p<0.0001). For patients achieving myeloid recovery, the median time of engraftment was 16 days when donor chimerism at day + 14 was higher than 90%, compared with 24 days when donor chimerism was below this level (p<0.001). A donor chimerism level of 65% was found to be the best cut-off point for predicting primary graft failure, with a sensitivity of 97% and a specificity of 80%. The incidence of primary graft failure was 67% for patients with less than 65% donor chimerism at day +14 as compared to only 2% for those with more than 65% donor chimerism (p<0.001). Patients with mixed chimerism also had a lower cumulative incidence of platelet engraftment than those with complete chimerism (62% vs. 89%; p=0.01). CONCLUSIONS: Donor-recipient chimerism status at day +14 predicts engraftment after a single-unit cord blood transplant in adults.

PMID: 19483157 [PubMed - in process]

PMCID: PMC2688574


3. [Therapeutic use and profile of toxicity of the FOLFOX4 regimen.]

[Article in Spanish]

Fernández-Lobato B, Díaz-Carrasco MS, Pareja A, Marín M, Vila N, de la Rubia A.
Servicio de Farmacia, Hospital Universitario Virgen de la Arrixaca, Murcia, España.

INTRODUCTION: Since the publication of the MOSAIC test results in 2004, the FOLFOX4 regimen has been established as an adjuvant treatment which is recommended in stage III colorectal cancer. The aim of this study is to assess the use of this regimen in our field and to describe its toxicity. METHODS: Descriptive study of treatments with FOLFOX4 prescribed between April 2005 and March 2007. The data was obtained from the Farhos Oncología(R) programme and clinical records. The following data was collected: age, gender, diagnosis, stage of the illness (TNM classification) and adverse reactions, expressing severity according to Common Toxicity Criteria 2.0. RESULTS: The FOLFOX4 regimen was prescribed for 39 patients (24 men and 15 women) with an average age of 59. The diagnoses were: 28 colon cancer (4 stage II, 17 stage III, and 7 stage IV), 10 rectal cancer (1 stage II, 4 stage III, and 5 stage IV) and 1 stage IV gastric cancer. The most frequent adverse reactions were peripheral neuropathy (82 %), neutropenia (56.4 %) and diarrhoea (53.9 %.) When the study was completed, 9 patients continued active treatment with the regimen (average 6.8 cycles.) Of the 30 remaining patients only 16 people completed the 12 planned cycles. 14 patients stopped their treatment (an average of 8.1 cycles) due to toxicity in 10 cases, clinical progression in 3 cases and one patient died. Of the total 368 cycles administered, 68 suffered administration delays and 22 had the dosage reduced. CONCLUSION: The use of the FOLFOX4 regimen has been adjusted to uses with some solid scientific evidence, but its toxicity has limited its use and has made administering the planned dosage levels difficult.

PMID: 19480796 [PubMed - in process]

4. Incidence, risk factors, and outcome of cytomegalovirus infection and disease in patients receiving prophylaxis with oral valganciclovir or intravenous ganciclovir after umbilical cord blood transplantation.

Montesinos P, Sanz J, Cantero S, Lorenzo I, Martín G, Saavedra S, Palau J, Romero M, Montava A, Senent L, Martínez J, Jarque I, Salavert M, Córdoba J, Gómez L, Weiss S, Moscardó F, de la Rubia J, Larrea L, Sanz MA, Sanz GF.

Department of Hematology, Hospital Universitario La Fe, Valencia, Spain. montesinos_pau@gva.es

There is no information on the efficacy and safety of anticytomegalovirus (CMV) prophylaxis with intravenous ganciclovir or oral valganciclovir after unrelated cord-blood transplantation (UCBT). This issue was addressed in 151 adults (117 CMV-seropositive) undergoing UCBT at a single institution. The first 38 CMV-seropositive recipients were assigned to receive prophylactic ganciclovir, and the next 79 were given valganciclovir after engraftment. The cumulative incidence (CI) of CMV infection and disease was similar in patients receiving valganciclovir or ganciclovir (59% versus 55%, P = .59; and 9% versus 18%, P = .33, respectively). The toxicity profile and CI of nonrelapse mortality (CMV) and infection-related mortality did not differ between drugs. Patients receiving valganciclovir required fewer visits to the day hospital (P = .04). The CI of CMV infection and disease in 34 CMV-seronegative recipients was 12% and 6%, indicating that tight CMV monitoring is mandatory in this subset. The recipient's CMV serostatus, acute and extensive chronic graft-versus-host disease (aGVHD, cGVHD) were the main risk factors for CMV infection, and aGVHD for CMV disease. This study suggests that prophylaxis with oral valganciclovir is as safe and effective as intravenous ganciclovir for preventing CMV infection and disease after UCBT, but valganciclovir reduces the use of hospital resources.

PMID: 19450758 [PubMed - in process]

5. Evaluation of the hydrolytic-acidogenic step of a two-stage mesophilic anaerobic digestion process of sunflower oil cake.

De la Rubia MA, Raposo F, Rincón B, Borja R.

Instituto de la Grasa (CSIC), Avda. Padre García Tejero 4, 41012 Sevilla, Spain. arubia@cica.es

The influence of the hydraulic retention time (HRT) and organic loading rate (OLR) on the performance of the hydrolytic-acidogenic step of a two-stage anaerobic digestion process of sunflower oil cake (SuOC) were assessed. The experiments were performed in laboratory-scale completely stirred tank reactors at mesophilic (35 degrees C) temperature. Six OLR (ranging from 4 to 9 g VS L(-1) d(-1)) for four HRTs (8, 10, 12 and 15 days) were tested to check the effect of each operational variable. Based on the results obtained, it can be concluded that the hydrolysis yields obtained for all HRTs and OLRs assayed were in the range of 20.5-30.1%. In addition, the acidification degree of the substrate was mainly influenced by the OLR but not by the HRTs, the highest value (83.8%) being achieved for an HRT of 10 days and an OLR of 6 g VS L(-1) d(-1).

PMID: 19414248 [PubMed - in process]

6. The neurobiology of Meditation and its clinical effectiveness in psychiatric disorders.

Rubia K.

Institute of Psychiatry, Department of Child and Adolescent Psychiatry PO46, King's College University London, De Crespigny Park, London SE5 8AF, UK.

This paper reviews the evidence for changes of Meditation on body and brain physiology and for clinical effectiveness in disorders of psychiatry. The aim of Meditation is to reduce or eliminate irrelevant thought processes through training of internalised attention, thought to lead to physical and mental relaxation, stress reduction, psycho-emotional stability and enhanced concentration. Physiological evidence shows a reduction with Meditation of stress-related autonomic and endocrine measures, while neuroimaging studies demonstrate the functional up-regulation of brain regions of affect regulation and attention control. Clinical studies show some evidence for the effectiveness of Meditation in disorders of affect, anxiety and attention. The combined evidence from neurobiological and clinical studies seems promising. However, a more thorough understanding of the neurobiological mechanisms of action and clinical effectiveness of the different Meditative practices is needed before Meditative practices can be leveraged in the prevention and intervention of mental illness.

PMID: 19393712 [PubMed - as supplied by publisher]

7. Effect of single nucleotide polymorphisms of CAPN1 and CAST genes on meat traits in Nellore beef cattle (Bos indicus) and in their crosses with Bos taurus.

Curi RA, Chardulo LA, Mason MC, Arrigoni MD, Silveira AC, de Oliveira HN.

Departamento de Melhoramento e Nutrição Animal, Faculdade de Medicina Veterinária e Zootecnia, Universidade Estadual Paulista, Botucatu, SP 18618-000, Brazil.

Summary The objectives of this work were to study the segregation of single nucleotide polymorphisms of the calpain 1, large subunit (CAPN1) and calpastatin (CAST) genes in Nellore (Bos indicus) and Nellore xBos taurus beef cattle, as well as to evaluate their effects on meat traits. For this, 300 animals, including 114 Nellore, 67 Angus x Nellore, 44 Rubia Gallega x Nellore, 41 Canchim, 19 Brangus three-way crosses and 15 Braunvieh three-way crosses, were genotyped for the CAPN4751 [AF_248054.2:g.6545C>T (GenBank accession AF248054.2)] and CAST/DdeI [AF_159246.1:g.2959A>G (GenBank accession AF159246.1)] polymorphisms and phenotyped for Ribeye Area, Backfat Thickness, Intramuscular Fat, Shear Force (SF) and Myofibrillar Fragmentation Index (MFI). In relation to the CAPN4751 polymorphism, a frequency of 10.5% was observed for the C allele in the Nellore breed. In the total sample of studied animals, a significant association was found between genotypes and meat tenderness, assessed by SF (P = 0.005) and MFI (P = 0.008), with genotype CT being more favourable than TT. For the CAST/DdeI polymorphism, a frequency of 55.7% was found for the A allele in the Nellore breed. In the total sample, a significant association was observed between genotypes and meat tenderness - SF (P = 0.004) and MFI (P = 0.006), with genotype AA being more favourable than AG. The relationship between genotypes and aged meat tenderness in confluence with the distribution of favourable alleles shows great potential for application of the CAPN4751 and CAST/DdeI polymorphisms in the genetic improvement of the Nellore breed, whilst contributing to the validation, in this breed and in its crosses with B. taurus, of the association results previously described in the literature.

PMID: 19392828 [PubMed - as supplied by publisher]

8. 2D- and 3D-QSAR studies on 54 anti-tumor Rubiaceae-type cyclopeptides.

Yan H, Pan X, Tan N, Fan J, Zeng G, Han H.

State Key Laboratory of Phytochemistry and Plant Resources in West China, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming, Yunnan 650204, China; Graduate School of the Chinese Academy of Sciences, Beijing 100039, China.

RA-VII, a bicyclic hexapeptide isolated from the roots of Rubia cordifolia, Rubia akane belongs to Rubiaceae-type cyclopeptides (RAs) and has attracted much attention for its potent anti-tumor activity and its bicyclic structure incorporating the isodityrosine moiety. In this work, hologram quantitative structure-activity relationship (HQSAR), comparative molecular field analysis (CoMFA), and comparative molecular similarity indices analysis (CoMSIA) methods were employed to develop 2D- and 3D-QSAR models for 54 anti-tumor RAs. The LOO cross-validated q(2) values of HQSAR, CoMFA and CoMSIA models are 0.701, 0.510 and 0.613, respectively. The predictive ability of these models was validated by the test set including 7 RAs, and the predicted IC(50) values were in good agreement with the experimental IC(50) values. HQSAR result showed that chirality descriptor plays an important role in anti-tumor activity of RAs and OMe at R(1) and R(2) is necessary for increasing their activity. CoMFA and CoMSIA results demonstrated that small bulky and electropositive side chains at R(3) position and hydrophobic groups at R(7) and R(8) positions will increase their activity, and intra-molecular hydrogen bonds between residues 1 and 4 are necessary to maintain the pharmacophoric conformation of RAs. These results may be helpful in designing novel and potential anti-tumor RAs.

PMID: 19303172 [PubMed - as supplied by publisher]

9. Exercise may cause myocardial ischemia at the anaerobic threshold in cardiac rehabilitation programs.

Fuchs AR, Meneghelo RS, Stefanini E, De Paola AV, Smanio PE, Mastrocolla LE, Ferraz AS, Buglia S, Piegas LS, Carvalho AA.

Serviço de Reabilitação Cardiovascular, Instituto Dante Pazzanese de Cardiologia, São Paulo, SP, Brasil. rubia.fuchs@hotmail.com

Myocardial ischemia may occur during an exercise session in cardiac rehabilitation programs. However, it has not been established whether it is elicited when exercise prescription is based on heart rate corresponding to the anaerobic threshold as measured by cardiopulmonary exercise testing. Our objective was to determine the incidence of myocardial ischemia in cardiac rehabilitation programs according to myocardial perfusion SPECT in exercise programs based on the anaerobic threshold. Thirty-nine patients (35 men and 4 women) diagnosed with coronary artery disease by coronary angiography and stress technetium-99m-sestamibi gated SPECT associated with a baseline cardiopulmonary exercise test were assessed. Ages ranged from 45 to 75 years. A second cardiopulmonary exercise test determined training intensity at the anaerobic threshold. Repeat gated-SPECT was obtained after a third cardiopulmonary exercise test at the prescribed workload and heart rate. Myocardial perfusion images were analyzed using a score system of 6.4 at rest, 13.9 at peak stress, and 10.7 during the prescribed exercise (P < 0.05). The presence of myocardial ischemia during exercise was defined as a difference > or = 2 between the summed stress score and summed rest score. Accordingly, 25 (64%) patients were classified as ischemic and 14 (36%) as nonischemic. MIBI-SPECT showed myocardial ischemia during exercise within the anaerobic threshold. The 64% prevalence of ischemia observed in the study should not be looked on as representative of the whole population of patients undergoing exercise programs. Changes in patient care and exercise programs were implemented as a result of our finding of ischemia during the prescribed exercise.

PMID: 19287906 [PubMed - in process]

10. Imipenem/cilastatin with or without glycopeptide as initial antibiotic therapy for recipients of autologous stem cell transplantation: results of a Spanish multicenter study.

de la Rubia J, Montesinos P, Martino R, Jarque I, Rovira M, Vázquez L, López J, Batlle M, de la Cámara R, Juliá A, Lahuerta JJ, Debén G, Díaz J, García R, Sanz MA.

Hospital La Fe, Valencia, Spain.

We analyzed the efficacy of imipenem/cilastatin alone (group I, 197 patients) or in combination with a glycopeptide (group I + G, 231 patients) as first-line antibiotic therapy for 2 consecutive cohorts of autologous stem cell transplantation (ASCT) recipients with febrile neutropenia. From June 2001 to June 2002, patients received imipenem/cilastatin (500 mg/6 hours), and from July 2002 to December 2003, they received imipenem/cilastatin as for group I plus a glycopeptide (vancomycin, 1 g/12 hours or teicoplanin, 400 mg/day). Fever of unknown origin accounted for 33.5% of episodes (66 patients) in group I and 50% of episodes (116 patients) in group I + G (P = .005). Bacteremia occurred in 55 patients (28%) in group I and in 51 patients (22%) in group I + G (P = .16). Resolution of fever without modification of the therapy regimen was observed in 108 patients (55%) and 159 patients (69%) in groups I and I + G, respectively (P = .003). The median interval to defervescence (4 days) and overall mortality were similar between groups. Inclusion of a glycopeptide in the initial antibiotic regimen for febrile neutropenia results in a higher success rate without modifying the regimen. However, glycopeptide inclusion does not improve the interval to defervescence or mortality rate.

PMID: 19285640 [PubMed - indexed for MEDLINE]

11. Shared and disorder-specific prefrontal abnormalities in boys with pure attention-deficit/hyperactivity disorder compared to boys with pure CD during interference inhibition and attention allocation.

Rubia K, Halari R, Smith AB, Mohammad M, Scott S, Brammer MJ.

Department of Child Psychiatry, Institute of Psychiatry, King's College, London, UK.

Background: Inhibitory and attention deficits have been suggested to be shared problems of disruptive behaviour disorders. Patients with attention deficit hyperactivity disorder (ADHD) and patients with conduct disorder (CD) show deficits in tasks of attention allocation and interference inhibition. However, functional magnetic resonance imaging (fMRI) of inhibitory and attention control has only been investigated in patients with ADHD, including comorbidity with CD, finding fronto-striatal and temporo-parietal dysfunction. This study investigates differences and commonalities in functional neural networks mediating interference inhibition and attention allocation between medication-naïve children and adolescents with pure CD and those with pure ADHD. Methods: Event-related fMRI was used to compare brain activation of 13 boys with non-comorbid CD, 20 boys with non-comorbid ADHD and 20 healthy comparison boys during a Simon task that measures interference inhibition and controls for attention allocation, thus tapping into interference inhibition and selective attention networks. Results: During interference inhibition, both patient groups shared reduced activation compared to controls in right superior temporal lobe and in predominantly right precuneus. During the oddball condition, both patient groups showed reduced activation compared to healthy control children in right medial prefrontal lobe. However, only ADHD patients showed a disorder-specific under-activation compared to the other two groups in an extensive activation cluster in left inferior prefrontal cortex. Conclusions: This study shows shared dysfunction in both patients groups in right hemispheric temporal and parietal brain regions during interference inhibition and in right dorsolateral prefrontal cortex during attention allocation. Ventrolateral prefrontal dysfunction, however, was specific to ADHD and not observed in patients with CD in the context of attention allocation. The findings suggest that the typically reduced functional activation in patients with ADHD in ventrolateral prefrontal cortex may be specific to the disorder, at least when compared to patients with CD.

PMID: 19236528 [PubMed - as supplied by publisher]


12. Total red blood cell concentrations of omega-3 fatty acids are associated with emotion-elicited neural activity in adolescent boys with attention-deficit hyperactivity disorder.

Gow RV, Matsudaira T, Taylor E, Rubia K, Crawford M, Ghebremeskel K, Ibrahimovic A, Vallée-Tourangeau F, Williams LM, Sumich A.

Department of Child and Adolescent Psychiatry, PO Box 85, Institute of Psychiatry, De Crespigny Park, Denmark Hill, London SE58AF, UK. Rachel.gow@iop.kcl.ac.uk

Affective impairment is observed in children and adolescents with attention-deficit hyperactivity disorder (ADHD). Low levels of long-chain polyunsaturated fatty acids (LC-PUFA), specifically omega-3 (omega-3) fatty acids in blood measures have been linked to a range of behavioural and mood disorders including ADHD. However, nothing is known about the relationship between omega-3 and brain function in children with ADHD. In the current study, 20 adolescent boys with ADHD were assessed for total lipid fractions in red blood cells and their event-related potential (ERP) response to the presentation of facial expressions of happiness, sadness and fearfulness. The results supported the hypothesis of a positive association between eicosapentaenoic acid (EPA) and a cognitive bias in orientation to overt expressions of happiness over both sad and fearful faces as indexed by midline frontal P300 amplitude. Additional exploratory analyses revealed a positive association between levels of docosahexaenoic acid (DHA) and the right temporal N170 amplitude in response to covert expressions of fear. The arachidonic (AA)/DHA ratio was negatively associated with the right temporal N170 amplitude also to covert expressions of fear. These findings indicate that EPA and DHA may be involved in distinct aspects of affect processing in ADHD and have implications for understanding currently inconsistent findings in the literature on EFA supplementation in ADHD and depression.

PMID: 19230637 [PubMed - in process]

13. Newly diagnosed versus relapsed idiopathic thrombotic thrombocytopenic purpura: a comparison of presenting clinical characteristics and response to treatment.

Alvarez-Larrán A, Del Río-Garma J, Pujol M, de la Rubia J, Hernández-Jodra M, Borrell M, González-Porras JR, García-Gala JM, Viejo A, Enríquez L, Arbona C, García-Erce JA, Noblejas AG, Pereira A.

Hospital del Mar, Barcelona, Spain.

The remission rate with plasma exchange (PE) in thrombotic thrombocytopenic purpura (TTP) exceeds 80%, but the disease relapses in up to 20-30% of the cases. Clinical characteristics and response to treatment of relapsed TTP are not well defined. The objective of the present study was to compare the clinical and biological characteristics at presentation and the response to treatment between de novo and relapsed TTP. For such purpose, a total of 102 episodes of idiopathic TTP (70 de novo and 32 relapses) included in a recent multicentric prospective cohort study were analysed. All patients were homogeneously treated with daily PE and costicosteroids. In comparison with de novo TTP, episodes of relapsed TTP showed a higher Hb level (median, 122 g/l versus 91 g/l, p < 0.001) and lower serum lactate dehydrogenase (2.2- versus 4.5-fold above the upper limit of normality, p < 0.001). Neurological symptoms and fever were less frequently observed in patients with relapsed TTP than in patients with de novo TTP. Patients with relapsed TTP needed fewer PE sessions (five versus ten, p = 0.02) and a smaller volume of plasma (221 ml/kg versus 468 ml/kg, p = 0.004) to achieve remission than those with de novo TTP. There was no significant difference in the rate of recrudescence under treatment, the need of complementary treatments or the frequency of refractoriness to PE therapy. In conclusion, relapsed TTP has a milder clinical profile and responds more easily to PE than de novo TTP.

PMID: 19205654 [PubMed - as supplied by publisher]

14. Single daily dose of intravenous busulfan and melphalan as a conditioning regimen for patients with multiple myeloma undergoing autologous stem cell transplantation: a phase II trial.

Blanes M, de la Rubia J, Lahuerta JJ, González JD, Ribas P, Solano C, Alegre A, Sanz MA.

Hematology Service, University Hospital La Fe, Valencia, Spain.

We evaluated the toxicity and outcome of a conditioning regimen comprising intravenous (iv) busulfan (BU) and melphalan (MEL) in 55 patients (median age, 61 years; range, 34-71) with multiple myeloma (MM) undergoing autologous stem-cell transplantation (ASCT). In 49 patients, this was the first ASCT. At transplant, 3 patients were in complete response (CR), 8 in near CR (nCR) and 30 in partial response (PR). The conditioning regimen comprised ivBU (3.2 mg/kg in a single daily dose, days -5 to -3) and MEL (140 mg/m(2), day -2). Mucositis was the most frequent non-hematopoietic toxicity (47 patients). No patient developed sinusoidal occlusive syndrome. Febrile events were observed in 46 patients and were the cause of death in two (3.6%) transplant-related deaths. With a median follow-up of 15 months, 27 patients achieved CR/nCR (11 CR) and 21 a PR. The one-year actuarial overall and progression-free survival rates are 96% and 87%, respectively. This ivBU-containing regimen is associated with an acceptable toxicity and a high-response rate.

PMID: 19197734 [PubMed - indexed for MEDLINE]

15. Reduced activation in lateral prefrontal cortex and anterior cingulate during attention and cognitive control functions in medication-naïve adolescents with depression compared to controls.

Halari R, Simic M, Pariante CM, Papadopoulos A, Cleare A, Brammer M, Fombonne E, Rubia K.

Child and Adolescent Psychiatry, Institute of Psychiatry, London, UK. r.halari@iop.kcl.ac.uk

BACKGROUND: There is increasing recognition of major depressive disorder (MDD) in adolescence. In adult MDD, abnormalities of fronto-striatal and fronto-cingulate circuitries mediating cognitive control functions have been implicated in the pathogenesis and been related to problems with controlling negative thoughts. No neuroimaging studies of cognitive control functions, however, exist in paediatric depression. This study investigated whether medication-naïve adolescents with MDD show abnormal brain activation of fronto-striatal and fronto-cingulate networks when performing tasks of attentional and cognitive control. METHODS: Event-related functional magnetic resonance imaging was used to compare brain activation between 21 medication-naïve adolescents with a first-episode of MDD aged 14-17 years and 21 healthy adolescents, matched for handedness, age, sex, demographics and IQ. Activation paradigms were tasks of selective attention (Simon task), attentional switching (Switch task), and motor response inhibition and error detection (Stop task). RESULTS: In all three tasks, adolescents with depression compared to healthy controls demonstrated reduced activation in task-relevant right dorsolateral (DLPFC), inferior prefrontal cortex (IFC) and anterior cingulate gyrus (ACG). Additional areas of relatively reduced activation were in the parietal lobes during the Stop and Switch tasks, putamen, insula and temporal lobes during the Switch task and precuneus during the Simon task. CONCLUSIONS: This study shows first evidence that medication-naïve adolescents with MDD are characterised by abnormal function in ACG and right lateral prefrontal cortex during tasks of attention and performance monitoring, suggesting an early pathogenesis of these functional abnormalities attributed to MDD.

PMID: 19175815 [PubMed - in process]

16. Rubiacordone A: a new anthraquinone glycoside from the roots of Rubia cordifolia.

Li X, Liu Z, Chen Y, Wang LJ, Zheng YN, Sun GZ, Ruan CC.

College of Chinese Medicinal Materials, Jilin Agricultural University, Changchun, PR China. drxiang@hotmail.com

A new anthraquinone, Rubiacordone A (1) (6-acetoxy-1-hydroxy-2-methylanthraquinone-3-O-alpha-L-rhamnopyranoside), was isolated together with the known anthraquinone, 1-acetoxy-6-hydroxy-2-methylanthraquinone-3-O-[alpha-L-rhamnopyranosyl-(1-->2)-beta-D-glucopyranoside] (2), from the dried roots of Rubia cordifolia. Their structures were elucidated on the basis of extensive 1D and 2D-NMR, as well as HRESI-MS spectroscopic analysis. Metabolites 1 and 2 showed considerable antimicrobial activity against Gram-positive bacteria.

PMID: 19169203 [PubMed - indexed for MEDLINE]

17. Possible contribution of rubiadin, a metabolite of madder color, to renal carcinogenesis in rats.

Inoue K, Yoshida M, Takahashi M, Fujimoto H, Ohnishi K, Nakashima K, Shibutani M, Hirose M, Nishikawa A.

Division of Pathology, National Institute of Health Sciences, Tokyo, Japan. k-inoue@nihs.go.jp

Madder color (MC) has been shown to exert carcinogenic potential in the rat kidney in association with degeneration, karyomegaly, increased cell proliferation of renal tubule cells and increased renal 8-OHdG levels. To clarify the causal relationship of components and metabolites of MC to renal carcinogenesis, male F344 rats were fed lucidin-3-O-primeveroside (LuP) or alizarin (Alz), and the genotoxic LuP metabolites lucidin (Luc) or rubiadin (Rub) for up to 26 weeks. After one week and four weeks, Luc did not induce any renal changes. In contrast, after one week, cortical tubule degeneration was apparent in the Alz and LuP groups, and cytoplasmic swelling with basophilic change and karyomegaly in the outer medulla was observed only in the Rub group. LuP and Rub increased the proliferative activity of tubule cells in the outer medulla, and Alz and LuP increased renal 8-OHdG levels. After 26 weeks, Rub but not Alz induced atypical tubules, a putative preneoplastic lesion, and karyomegaly in the outer medulla. These results indicate that Rub may be a potent carcinogenic metabolite of MC, targeting proximal tubule cells in the outer medulla, although oxidative stress increased by Alz or LuP might also be involved in renal carcinogenesis by MC.

PMID: 19167447 [PubMed - indexed for MEDLINE]

18. [Pharmacoeconomic results of introducing antimicrobial prophylaxis in surgery at a university hospital.]

García-Vázquez E, Fernández Lobato B, Pareja A, Gómez J, de la Rubia A.

Servicio de MI-Infecciosas. Hospital Universitario Virgen de la Arrixaca. El Palmar. Murcia. España. elisag@eresmas.net.

OBJECTIVES: The introduction of antimicrobial prophylaxis in surgery was designed and pre-intervention (controls) and post-intervention (cases) evaluations were carried out at a university tertiary hospital. PATIENTS AND METHOD: Prospective recording of information on prophylaxis in all patients undergoing non-emergency abdominal surgery was analysed during a 3-week period before and after implementing an antimicrobial prophylaxis program. Adequacy of prophylaxis was defined as prescription of antibiotics (type, dose and duration of treatment) according to the Guidelines. RESULTS: In the pre-intervention study: included 36 patients; prophylaxis was inadequate in all patients (long-term in 22 cases; antibiotic class and long-term in 2 cases; antibiotic class, dose and long-term in 12 cases); mean duration of prophylaxis was 6 days (range 1 to 10 days); mean antibiotic cost per patient was 77 euro (range 9 to 412 euro); overall antibiotic cost for the 36 patients was 2770 euro. In the post-intervention study: included 37 patients: prophylaxis was inadequate in 11 patients (long-term in 10 cases; antibiotic class and long-term in 1 case); mean duration of prophylaxis was 2 days (range 1 to 9 days); mean antibiotic cost per patient was 16 euro (range 2 to 78 euro); overall antibiotic cost for the 37 patients was 593 euro. In the pre-intervention period antibiotic cost was 38 times higher than expected. In the post-intervention period it was 1.6 times higher than expected. CONCLUSIONS: The most common reason of prophylaxis inadequacy is prolonged antibiotic treatment. A multidisciplinary intervention that comprises infectious diseases, surgical and pharmacy departments improves prophylaxis prescribing practice and avoids erroneous prescribing of antibiotics with both microbiological and economical cost savings.

PMID: 19087780 [PubMed - in process]


19. Induction of kidney and liver cancers by the natural food additive madder color in a two-year rat carcinogenicity study.

Inoue K, Yoshida M, Takahashi M, Shibutani M, Takagi H, Hirose M, Nishikawa A.

Division of Pathology, National Institute of Health Sciences, 1-18-1 Kamiyoga, Setagaya-ku, Tokyo 158-8501, Japan. k-inoue@nihs.go.jp

Madder color (MC) extracted from the roots of Rubia tinctorum (madder root) has been used as a food coloring in Japan. Our previous studies revealed MC to have obvious subchronic and chronic toxicity and potent carcinogenicity targeting rat liver and kidney. In the present two-year carcinogenicity study, conducted to further elucidate the long-term effects of MC and its target organs, male and female F344 rats were fed diet containing 0%, 2.5%, and 5.0% MC for 104 weeks. Body weights were significantly decreased in treated groups of both sexes throughout the feeding period. However, survival rates at week 104 were higher in treated groups of both sexes than in controls. Relative weights of the kidneys and liver were significantly increased in treated groups of both sexes. Histopathologically, karyomegaly and atypical tubules/hyperplasias, as well as renal cell adenomas and carcinomas were significantly increased in treated groups of both sexes with dose-dependence. Moreover, the incidence of hepatocellular adenomas and/or carcinomas was increased significantly with a dose-relation in treated groups of both sexes. These data provide clear evidence that MC exerts unequivocal carcinogenicity against renal tubule cells and hepatocytes in rats.

PMID: 19032970 [PubMed - indexed for MEDLINE]


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