Inventario PID-5, perfil dimensional del DSM5 para orientar el diagnóstico y las necesidades terapéuticas en los trastornos de personalidad / The PID -5 Inventory: the dimensional profile of DSM5 to guide diagnosis and therapeutic needs in personality disorders

El Inventario PID-5 de la American Psychiatric Association, evalúa la personalidad y sus trastornos desde el modelo dimensional de rasgos (DSM-5 Sección III), orientando el diagnóstico y las necesidades terapéuticas individuales. Analizamos la utilidad de su aplicación en pacientes derivados a un Hospital de Día para Trastornos de Personalidad (Clústers B y C). En la muestra de 85 sujetos, 51 % son Trastorno Límite (TLP) y 47 % Trastorno de Personalidad No Especificado/Mixto (TPNE/TPM), presentando el 65 % trastornos clínicos comórbidos. Del grupo TLP 89 % son mujeres, 53 % menores de 30 años; en el PID-5 presentan un perfil de mayor gravedad, destacando los Dominios Afecto Negativo y Desinhibición, y las facetas depresión, impulsividad, anhedonia y distraibilidad. Presentan mayor intensidad de síntomas límite (Cuestionario BEST), utilizan menos estrategias de afrontamiento de síntomas y más estrategias de evitación (Cuestionario COPE-28). En el TPNE/TPM, el 58 % son mujeres, 80 % mayores de 30 años, en su perfil del PID-5 destaca afectividad negativa, especialmente la faceta ansiedad. Ambos grupos muestran rasgos límites y evitativos en el screening IPDE. El PID-5 se ha mostrado útil para confirmar diagnósticos específicos (TLP), también para describir el perfil de rasgos y plantear las necesidades terapéuticas concretas tanto en TLP como en TPNE/TPM

The PID-5 Inventory of the American Psychiatric Association evaluates personality and related disorders based on the dimensional trait model (DSM-5 Section III), which guides individual diagnosis and therapeutic needs. We analysed its usefulness as it was applied to patients that had been referred to a Day Hospital for Personality Disorders. In the sample of 85 subjects, 51 % had Borderline Personality Disorder (BPD), and 47 % had Personality Disorder NOS or Mixed (PD-NOS/MP), 65 % presenting comorbid clinical disorders. Among the BPD group, 89 % were women, 53 % were under 30 years old; they presented a PID-5 profile of greater severity, the Negative Affect and Disinhibition Domains stood out, as well as the facets of depression, impulsivity, anhedonia and distraction. Their borderline symptoms (BEST scale) were of greater intensity, they used fewer symptom coping strategies and more avoidance strategies (COPE-28 inventory). Among the PD-NOS/MP group, 58 % are women, 80 % were aged over 30 years, and negative affectivity, especially anxiety, stood out in their PID-5 profile. Both groups show borderline and avoidant features in the IPDE screening. The PID-5 was useful for confirming specific diagnoses (BPD), for describing the trait profile as well as proposing the specific therapeutic needs of both BPD and PD-NOS/MP patients

Tax secretion from peripheral blood mononuclear cells and Tax detection in plasma of patients with human T-lymphotropic virus-type 1-associated myelopathy/tropical spastic paraparesis and asymptomatic carriers.

Human T-lymphotropic virus-type 1 (HTLV-1) is the etiologic agent of the neurologic disease HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Tax viral protein plays a critical role in viral pathogenesis. Previous studies suggested that extracellular Tax might involve cytokine-like extracellular effects. We evaluated Tax secretion in 18 h-ex vivo peripheral blood mononuclear cells (PBMCs) cultures from 15 HAM/TSP patients and 15 asymptomatic carriers. Futhermore, Tax plasma level was evaluated from other 12 HAM/TSP patients and 10 asymptomatic carriers. Proviral load and mRNA encoding Tax were quantified by PCR and real-time RT-PCR, respectively. Intracellular Tax in CD4(+)CD25(+) cells occurred in 100% and 86.7% of HAM/TSP patients and asymptomatic carriers, respectively. Percentage of CD4(+)CD25(+) Tax+, proviral load and mRNA encoding Tax were significantly higher in HAM/TSP patients. Western blot analyses showed higher secretion levels of ubiquitinated Tax in HAM/TSP patients than in asymptomatic carriers. In HTLV-1-infected subjects, Western blot of plasma Tax showed higher levels in HAM/TSP patients than in asymptomatic carriers, whereas no Tax was found in non-infected subjects. Immunoprecipitated plasma Tax resolved on SDS-PAGE gave two major bands of 57 and 48 kDa allowing identification of Tax and Ubiquitin peptides by mass spectrometry. Relative percentage of either CD4(+)CD25(+) Tax+ cells, or Tax protein released from PBMCs, or plasma Tax, correlates neither with tax mRNA nor with proviral load. This fact could be explained by a complex regulation of Tax expression. Tax secreted from PBMCs or present in plasma could potentially become a biomarker to distinguish between HAM/TSP patients and asymptomatic carriers.

Pro-oxidant status and matrix metalloproteinases in apical lesions and gingival crevicular fluid as potential biomarkers for asymptomatic apical periodontitis and endodontic treatment response.

BACKGROUND: Oxidative stress and matrix metalloproteinases -9 and -2 are involved in periodontal breakdown, whereas gingival crevicular fluid has been reported to reflect apical status. The aim of this study was to characterize oxidant balance and activity levels of MMP -2 and -9 in apical lesions and healthy periodontal ligament; and second, to determine whether potential changes in oxidant balance were reflected in gingival crevicular fluid from asymptomatic apical periodontitis (AAP)-affected teeth at baseline and after endodontic treatment. METHODS: Patients with clinical diagnosis of AAP and healthy volunteers having indication of tooth extraction were recruited. Apical lesions and healthy periodontal ligaments, respectively, were homogenized or processed to obtain histological tissue sections. Matrix metalloproteinase -9 and -2 levels and/or activity were analyzed by Immunowestern blot, zymography and consecutive densitometric analysis, and their tissue localization was confirmed by immunohistochemistry. A second group of patients with AAP and indication of endodontic treatment was recruited. Gingival crevicular fluid was extracted from AAP-affected teeth at baseline, after endodontic treatment and healthy contralateral teeth. Total oxidant and antioxidant status were determined in homogenized tissue and GCF samples. Statistical analysis was performed using STATA v10 software with unpaired t test, Mann-Whitney test and Spearman's correlation. RESULTS: Activity of MMP-2 and MMP-9 along with oxidant status were higher in apical lesions (p < 0.05). Total oxidant status correlated positively with matrix metalloproteinase-2 and lesion size (p < 0.05). Gingival crevicular fluid showed significantly lower levels of total antioxidant status in diseased teeth at baseline compared to controls and endodontically-treated groups. CONCLUSIONS: Apical lesions display an oxidant imbalance along with increased activity of matrix metalloproteinase-2 and -9 and might contribute to AAP progression. Oxidant imbalance can also be reflected in GCF from AAP-affected teeth and was restored to normal levels after conservative endodontic treatment. These mediators might be useful as potential biomarkers for chair-side complementary diagnostic of apical status in GCF.

Molecular and clinical effects of betamethasone in human T-cell lymphotropic virus type-I-associated myelopathy/tropical spastic paraparesis patients.

There is no effective therapy for human T-cell lymphotropic virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP). Glucocorticoids are effective to reduce the motor disability in these patients, but its role as anti-spastic drugs is unknown. Here it is reported the use of corticosteroids in HAM/TSP. The goal was to find reliable molecular markers linked to treatment effectiveness. The clinical efficacy of corticosteroids was studied in 22 HAM/TSP. The treatment was a single dose of 7.0 mg of systemic betamethasone. Pre-treatment samples were obtained immediately before steroid administration and post-treatment samples were collected after 5 days. Neurological disability was evaluated by the Osame's Motor Disability Scales. Relative levels of Tax, Foxp3, IL-10, TGF-ß, CTLA-4, and GITR mRNA were measured and the percentage of CD4(+) Foxp3(+) and CD4(+) Tax(+) populations was quantified in PBMCs by real-time PCR and flow cytometry, respectively. The same parameters were studied in eight untreated carriers. Betamethasone treatment showed neurological improvement in 21 HAM/TSP patients, with one patient without response to treatment. This therapy was associated with a decrease in Tax mRNA load and CD4(+) Tax(+) T cells in HAM/TSP. Simultaneously, an increase in Foxp3 mRNA and CD4(+) Foxp3(+) T cell was detected in these patients. The other markers studied had no significant changes after treatment. Clinical improvement in betamethasone-treated HAM/TSP was associated with an inverse relationship between a decrease in Tax and an increase in Foxp3 at the mRNA and protein levels. These results suggest that both Tax and Foxp3 may represent potential biomarkers for drug treatment assessments in HAM/TSP.

Inhibition of cyclin-dependent kinase 5 but not of glycogen synthase kinase 3-ß prevents neurite retraction and tau hyperphosphorylation caused by secretable products of human T-cell leukemia virus type I-infected lymphocytes.

Human T-cell leukemia virus type I (HTLV-I)-associated myelopathy/tropical spastic paraparesis (HAM/TSP) is a neurodegenerative disease characterized by selective loss of axons and myelin in the corticospinal tracts. This central axonopathy may originate from the impairment of anterograde axoplasmic transport. Previous work showed tau hyperphosphorylation at T(181) in cerebrospinal fluid of HAM/TSP patients. Similar hyperphosphorylation occurs in SH-SY5Y cells incubated with supernatant from MT-2 cells (HTLV-I-infected lymphocytes secreting viral proteins, including Tax) that produce neurite shortening. Tau phosphorylation at T(181) is attributable to glycogen synthase kinase 3-ß (GSK3-ß) and cyclin-dependent kinase 5 (CDK5) activation. Here we investigate whether neurite retraction in the SH-SY5Y model associates with concurrent changes in other tau hyperphosphorylable residues. Threonine 181 turned out to be the only tau hyperphosphorylated residue. We also evaluate the role of GSK3-ß and CDK5 in this process by using specific kinase inhibitors (LiCl, TDZD-8, and roscovitine). Changes in both GSK3-ß active and inactive forms were followed by measuring the regulatory phosphorylable sites (S(9) and Y(216) , inactivating and activating phosphorylation, respectively) together with changes in ß-catenin protein levels. Our results showed that LiCl and TDZD-8 were unable to prevent MT-2 supernatant-mediated neurite retraction and also that neither Y(216) nor S(9) phosphorylations were changed in GSK3-ß. Thus, GSK3-ß seems not to play a role in T(181) hyperphosphorylation. On the other hand, the CDK5 involvement in tau phosphorylation was confirmed by both the increase in its enzymatic activity and the absence of MT-2 neurite retraction in the presence of roscovitine or CDK5 siRNA transfection.

Application of capillary electrophoresis for the identification of Atlantic salmon and rainbow trout under raw and heat treatment.

Accurate authentication of related species is necessary to prevent the illegal replacement of species of higher quality and/or price with lower-quality, less expensive species. Atlantic salmon (Salmo salar), an expensive and valuable species, can be intentionally substituted with rainbow trout (Oncorhynchus mykiss). Using the technique of capillary zone electrophoresis (CZE), the identification of raw species was based on the analysis of muscle sarcoplasmic (water-soluble) proteins, while for canned species identification was based on muscle proteins solubilized with urea and sodium dodecyl sulfate (SDS). Either water or urea-SDS extracted proteins gave reproducible and distinct electrophoretic patterns of proteins for both species independent of storage conditions. Although data analysis indicated changes in protein profiles for both species during storage, species identification was still possible. In addition, quality determination during refrigerated and frozen storage involved the use of two freshness indexes: K value (the relationship between inosine monophosphate, inosine, and hypoxantine) and pH. A linear correlation was found between changes in electrophoretic patterns and K values for refrigerated salmon species. Trout kept in storage for six days reached a constant K value higher than the maximum limit for a product of good quality, preventing determination of any correlation with electrophoretic pattern. The protein profiles obtained by CZE during long storage revealed their potential for monitoring both differences between fish species and changes in quality during refrigerated, frozen, and canned storage of the species under study.

Measurement of glycogen synthase activity in crude extracts by CE.

Glycogen synthase catalyzes the incorporation of UDP-glucose into glycogen. The activity of the enzyme is usually measured either by a spectrophotometric method or by a radioassay. The first one is not suitable because of the difficulties regarding the use of coupled enzymes in crude extracts, while the second is a time-consuming method involving glycogen isolation and manipulation of radioactivity. We have used a CZE technique as a novel approach to measure glycogen synthase activity. The separations were performed at 22 kV (36 microA) in uncoated capillaries (53 cmx50 microm). Sample injection time was 30 s and nucleotides were monitored at 254 nm. Best resolution was achieved in 20 mM tetraborate buffer, pH 9.2. Curves of absorbance as a function of UDP and UDP-glucose concentration were linear. Enzyme activity in oocyte extracts was linear with respect to time (up to15 min) and enzyme concentration. The K(m app.) for UDP-glucose was 0.87 mM, a value identical to the one reported using the radioassay. CZE enables easy quantitation of compounds, high sensitivity, and automation of the process. Small sample sizes are required, interferences by auxiliary enzymes and manipulation of radioactivity are avoided, and analysis time is significantly diminished.

[Optimization of the reduction of arterial blood pressure in essential hypertensives patients]. / Optimización de la reducción de la presión arterial en hipertensos esenciales.

BACKGROUND: A blood pressure below or equal to 140/90 mmHg, the aim of antihypertensive treatment, is rarely achieved. Only 16% of patients controlled by our group reach this goal. AIM: To analyze the causes of suboptimal treatment and to assess the effects of an optimization of antihypertensive therapy. PATIENTS AND METHODS: A random sample of 160 patients was analyzed and followed during one year. RESULTS: Sixty six patients (41%) had a normal blood pressure, maintained during the first three months of follow up. The main causes of suboptimal reduction of blood pressure in the remaining 94 patients were an incorrect prescription or dosage of medications in 37.5%, lack of compliance in 34%, insufficient delivery of medications by the health service in 24% and secondary effects of drugs in 5%. When these factors were corrected, blood pressure normalized in 41 of them. In other 37, a reduction of 5 mmHg or more in blood pressure, was obtained. The most frequent changes introduced were modifications in dosage and addition of a new medication. Therefore, in 90% of these patients, blood pressure was reduced or normalized. CONCLUSIONS: A correct identification of the cause of antihypertensive treatment failure is imperative. The correction of this cause leads to a further reduction in blood pressure in 90% of those subjects with suboptimal treatment.