The clock drawing test as a cognitive screening tool for assessment of hypertension-mediated brain damage.

INTRODUCTION: Hypertension (HTN) is the most frequent cause of subcortical vascular brain injury (VBI) and its cognitive consequences. The aims were to show the usefulness of the Clock Drawing Test (CDT) to detect cognitive impairment in hypertensive patients and to compare it with the Mini-Mental Test (MMSE). METHODS: A subset of hypertensive patients of the Heart-Brain Study in Argentina was included. Demographic characteristics, vascular risk factors, blood pressure (BP) and schooling level were recorded. The MMSE and CDT tests were used for neurocognitive assessment and Hospital Anxiety Depression scale (HAD) for mood disorder evaluation. RESULTS: 1414 hypertensive patients (age 59.7±13.8 years, female (62.3%). The prevalence of cognitive impairment was 20.7% (using MMSE) and 36.1% (using CDT). Among hypertensive patients with normal MMSE (>24) 29.3% had cognitive impairment (abnormal CDT). The CDT was associated with level of education but not with age or mood status. CONCLUSIONS: The CDT is a useful screening tool to detect hypertension-mediated brain damage earlier (especially in midlife) and is more sensitive than MMSE.

[The cognitive-behavioural impact of hypertension]. / El impacto cognitivo-conductual de la hipertensión.

Arterial hypertension is considered the main modifiable vascular risk factor that causes silent damage to brain vessels. This vascular brain injury could be the common nucleus that justifies the cognitive (cognitive impairment, dementia and Alzheimer's disease) and behavioural symptoms (late-life depression) of target organ damage mediated-hypertension. Incomplete knowledge about the complex pathophysiology that links hypertension with cognitive-behavioural changes is overlooking brain involvement and underestimating cardio and cerebrovascular risk. The confluence of cognitive impairment, depression and arterial hypertension in elderly adults, warns of the need for a comprehensive evaluation to plan treatment, improve prognosis and contribute to reducing the risk of dementia and its incidence.

Neurocognitive disorder in hypertensive patients. Heart-Brain Study.

The relation between hypertension and cognitive impairment is an undisputable fact. The aims of this study were to determine the prevalence of cognitive impairment in hypertensive patients, to identify the most affected cognitive domain, and to observe the association with different parameters of hypertension and other vascular risk factors. A multicentre study was carried out, and 1281 hypertensive patients of both genders and ≥21 years of age were included. Data on the following parameters were obtained: cognitive status (Minimal Cognitive Examination), behavioural status (Hospital Anxiety and Depression Scale), blood pressure, anthropometry, and biochemical profile. The average age was 60.2±13.5 years (71% female), and the educational level was 9.9±5.1 years. Global cognitive impairment was seen in 22.1%, executive dysfunction in 36.2%, and semantic memory impairment in 48.9%. Cognitive impairment was higher in males (36.8% vs. 30.06%) within both the 70-79-year-old and the ≥80-year-old (50% vs. 40%) age groups. Abnormal Clock Drawing Test results were related to high pulse pressure (p<0.0036), and abnormal Mini-Boston Naming Test results to both high systolic blood pressure (p<0.052) and pulse pressure (p<0.001). The treated/uncontrolled hypertensive group showed abnormal results both in the Mini Mental State Examination (OR, 0.73; p=0.036) and the Mini-Boston Naming Test (OR, 1.36; p=0.021). Among patients without cognitive impairment (MMSE >24), 29.4% presented executive dysfunction, and 41.5% semantic memory impairment. Cognitive impairment was higher in hypertensive patients than in the general population. Executive functions and semantic memory were the most affected cognitive domains. High systolic blood pressure and pulse pressure were associated with abnormal results in cognitive tests.

Factores de riesgo vascular y estado cognitivo en mujeres adultas / Vascular risk factors and cognitive status in adult women

INTRODUCCIÓN La enfermedad cardiovascular es la primera causa de muerte en mujeres en países desarrollados y también en la Argentina. Existen diferencias regionales y locales en la prevalencia de los factores de riesgo vascular y en relación a la edad y al sexo. Conocer estos determinantes de enfermedad tiene una indudable importancia sanitaria permitiendo reducir su impacto sobre la salud cardio y cerebrovascular (Deterioro cognitivo). MÉTODOS Estudio epidemiológico, transversal con muestreo polietápico en dos centros urbanos. RESULTADOS Población de 2560 mujeres con 49,48±0,31 años. Se detectó una prevalencia de hipertensión del 39%, tabaquismo 27%, sobrepeso u obesidad 75%, obesidad abdominal 68%, diabetes 11%, dislipemias 76%, sedentarismo 76% y deterioro cognitivo 20%. Todos los factores guardan una relación inversa con el nivel de instrucción, excepto el tabaquismo (p<0,01). Existe una asociación directa entre el deterioro cognitivo y la edad e inversa con el nivel de educación. La prevalencia de deterioro cognitivo fue 28,9% en >60 años y 17,6% en ≤60 años (p<0,01). Todos los factores de riesgo son más prevalentes en la mujer menopáusica independientemente de la edad (p<0,01). DISCUSIÓN Existen diferencias en la prevalencia de factores de riesgo vascular a nivel local, siendo mayor a la reportada nacionalmente, el deterioro cognitivo se asocia inversamente con el nivel de educación y la menopausia se asocia con mayor prevalencia de factores de riesgo independiente de la edad.

A rapid validated UV-HPLC method for the simultaneous determination of the antiretroviral compounds darunavir and raltegravir in their dosage form.

OBJECTIVE: A rapid, simple and sensitive high-performance liquid chromatography (HPLC) method with ultraviolet detection has been developed for quantification of darunavir and raltegravir in their pharmaceutical dosage form. METHODS: The assay enables the measurement of both drugs with a linear calibration curve (R2= 0.999) over the concentration range 5-100 mg/L. The determination was performed on an analytical Tracer Excel 120 ODSB (15x0.4.6 cm) column at 35ºC. The selected wavelength was 254 nm. The mobile phase was a mixture of 0.037 M sodium dihydrogen phosphate buffer, acetonitrile and methanol (40:50:10, v/v/v) at a flow rate of 2.0 mL/min Nevirapine (50 mg/L) was used as internal standard. RESULTS: Accuracy, intra-day repeatability (n = 5), and inter-day precision (n = 3) were found to be satisfactory, being the accuracy from -4.33 to 3.88% and precisions were intra-day and inter-day, 0.25% and 4.42% respectively in case of darunavir. Raltegravir intra-day and inter-day precisions lower of 1.01 and 2.36%, respectively and accuracy values bet from -4.02 to 1.06%. CONCLUSIONS: Determination of the darunavir and raltegravir in their dosage form was done with a maximum deviation of 4%. This analytical method is rapid, easily implantable and offers good results.

Pretransplant immediately early-1-specific T cell responses provide protection for CMV infection after kidney transplantation.

Cytomegalovirus (CMV) infection is still a major complication after kidney transplantation. Although cytotoxic CMV-specific T cells play a crucial role controlling CMV survival and replication, current pretransplant risk assessment for CMV infection is only based on donor/recipient (IgG)-serostatus. Here, we evaluated the usefulness of monitoring pre- and 6-month CMV-specific T cell responses against two dominant CMV antigens (IE-1 and pp65) and a CMV lysate, using an IFN-γ Elispot, for predicting the advent of CMV infection in two cohorts of 137 kidney transplant recipients either receiving routine prophylaxis (n = 39) or preemptive treatment (n = 98). Incidence of CMV antigenemia/disease within the prophylaxis and preemptive group was 28%/20% and 22%/12%, respectively. Patients developing CMV infection showed significantly lower anti-IE-1-specific T cell responses than those that did not in both groups (p < 0.05). In a ROC curve analysis, low pretransplant anti-IE-1-specific T cell responses predicted the risk of both primary and late-onset CMV infection with high sensitivity and specificity (AUC > 0.70). Furthermore, when using most sensitive and specific Elispot cut-off values, a higher than 80% and 90% sensitivity and negative predictive value was obtained, respectively. Monitoring IE-1-specific T cell responses before transplantation may be useful for predicting posttransplant risk of CMV infection, thus potentially guiding decision-making regarding CMV preventive treatment.

Dendritic cells phenotype fitting under hypoxia or lipopolysaccharide; adenosine 5'-triphosphate-binding cassette transporters far beyond an efflux pump.

This study examines adenosine 5'-triphosphate-binding cassette (ABC) transporters as a potential therapeutic target in dendritic cell (DC) modulation under hypoxia and lipopolysaccharide (LPS). Functional capacity of dendritic cells (DCs) (mixed lymphocyte reaction: MLR) and maturation of iDCs were evaluated in the presence or absence of specific ABC-transporter inhibitors. Monocyte-derived DCs were cultured in the presence of interleukin (IL)-4/granulocyte-macrophage colony-stimulating factor (GM-CSF). Their maturation under hypoxia or LPS conditions was evaluated by assessing the expression of maturation phenotypes using flow cytometry. The effect of ABC transporters on DC maturation was determined using specific inhibitors for multi-drug resistance (MDR1) and multi-drug resistance proteins (MRPs). Depending on their maturation status to elicit T cell alloresponses, the functional capacity of DCs was studied by MLR. Mature DCs showed higher P-glycoprotein (Pgp) expression with confocal microscopy. Up-regulation of maturation markers was observed in hypoxia and LPS-DC, defining two different DC subpopulation profiles, plasmacytoid versus conventional-like, respectively, and different cytokine release T helper type 2 (Th2) versus Th1, depending on the stimuli. Furthermore, hypoxia-DCs induced more B lymphocyte proliferation than control-iDC (56% versus 9%), while LPS-DCs induced more CD8-lymphocyte proliferation (67% versus 16%). ABC transporter-inhibitors strongly abrogated DC maturation [half maximal inhibitory concentration (IC50 ): P-glycoprotein inhibition using valspodar (PSC833) 5 µM, CAS 115104-28-4 (MK571) 50 µM and probenecid 2·5 µM], induced significantly less lymphocyte proliferation and reduced cytokine release compared with stimulated-DCs without inhibitors. We conclude that diverse stimuli, hypoxia or LPS induce different profiles in the maturation and functionality of DC. Pgp appears to play a role in these DC events. Thus, ABC-transporters emerge as potential targets in immunosuppressive therapies interfering with DCs maturation, thereby abrogating innate immune response when it is activated after ischaemia.

Determination of ganciclovir in human plasma by ultra performance liquid chromatography-UV detection.

OBJECTIVES: Implement a sensitive UHPLC method for the assay of ganciclovir in human plasma. DESIGN AND METHODS: We developed and validated a chromatographic method coupled to ultraviolet detection for quantification of ganciclovir, with a short run time using a small volume of human plasma. Comparison of system performance was made with respect to analysis time, efficiency and sensitivity. RESULTS: Correlation coefficients (r) of the calibration curves ranged from 0.999744 to 0.999784. Within-day and between-day imprecision and inaccuracy, specificity and recovery were also evaluated for validation. The method was precise and accurate and the retention time was 0.7 min. The calibration curves were linear between 0.5 and 30 µg/mL. There was a good correlation between HPLC and UHPLC techniques. CONCLUSIONS: We developed a method that is currently applied in a clinical study assessing GCV plasma concentration variability after ganciclovir and valganciclovir administration.

Pulmonary alveolar proteinosis: prolonged spontaneous remission in two patients.

Pulmonary alveolar proteinosis is a rare idiopathic diffuse airspace disease characterized by intra-alveolar accumulation of large quantities of lipoproteinaceous material, with preservation of the lung interstitium. The clinical course of pulmonary alveolar proteinosis is variable. Spontaneous resolution is known to occur in up to a quarter of the cases. We describe two patients with untreated pulmonary alveolar proteinosis who experienced complete clinical, functional and radiographic resolution. In follow-up periods of fourteen and six years, both patients have remained asymptomatic.