Tools for a personalized tacrolimus dose adjustment in the follow-up of renal transplant recipients. Metabolizing phenotype according to CYP3A genetic polymorphisms versus concentration-dose ratio.

Background And Justification: The strategy of the concentration-dose (C/D) approach and the different profiles of tacrolimus (Tac) according to the cytochrome P450 polymorphisms (CYPs) focus on the metabolism of Tac and are proposed as tools for the follow-up of transplant patients. The objective of this study is to analyse both strategies to confirm whether the stratification of patients according to the pharmacokinetic behaviour of C/D corresponds to the classification according to their CYP3A4/5 cluster metabolizer profile.

Materials And Methods: 425 kidney transplant patients who received Tac as immunosuppressive treatment have been included.

Predicting cognitive function and dementia risk in patients with hypertension.

In spite of the fact that hypertension stand out as the main vascular risk factor for developing dementia, it is essential to acknowledge the presence of other risk factors, both vascular and non-vascular that contribute to increase this risk. This study stratified the dementia risk using CAIDE (Cardiovascular Risk Factors, Aging, and Incidence of Dementia) dementia risk score in a sample of 1279 hypertensive patients from the Heart-Brain Study in Argentina and to observed the association between the risk factors include in the CAIDE score and the current cognitive status. The average age of the sample was 60.

[Arterial Hypertension, Structural Damage of the Brain and Cognitive Test].

Introduction: The arterial hypertension cause brain vascular damage (white matter lesion) and the burden and progression determine their cognitive consequences. Therefore, arterial hypertension is considered the main modifiable vascular risk factor for cognitive impairment and dementia. Therefore, the aim of the current study was to evaluate the results of cognitive tests in a sample of hypertensive patients and to establish possible associations with structural brain lesions (atrophy, white matter lesions) identified by magnetic resonance imaging

Methods: Were included 70 hypertensive patients from Heart-Brain study in Argentina with magnetic resonance imaging and cognitive test.

The Effect of Intracellular Tacrolimus Exposure on Calcineurin Inhibition in Immediate- and Extended-Release Tacrolimus Formulations.

Despite intensive monitoring of whole blood tacrolimus concentrations, acute rejection after kidney transplantation occurs during tacrolimus therapy. Intracellular tacrolimus concentrations could better reflect exposure at the site of action and its pharmacodynamics (PD). Intracellular pharmacokinetic (PK) profile following different tacrolimus formulations (immediate-release (TAC-IR) and extended-release (TAC-LCP)) remains unclear.

[Cognitive profile in hypertensive patients. Usefulness of the Clock Drawing Test].

Introduction: Hypertension is the main cause of cognitive impairment and the executive dysfunction the most com- mon cognitive domain affected. The aims of this research have been to characterize the cognitive profiles (s) in hypertensive patients and to identify the most usefulness Test (s) in the routine clinical practice to identify them.

Methods: We assessed the cognitive status in 69 hypertensive patients who were administered a battery of cognitive Tests that included the MMSE, the Mini-Boston Naming Test, verbal fluency and the Clock drawing Test.

[Prevalence of anxiety and depression in patients with cardiovascular disease during the COVID-19 pandemic].

Introduction: The COVID-19 pandemic and the sanitary measures implemented had an impact on the mental health of the most vulnerable populations.

Aims: To know the prevalence of anxiety and depression in patients with cardiovascular disease and/or vascular risk factors after the end of quarantine and compare it with the prevalence during quarantine and before the COVID-19 pandemic.

Methods: An online questionnaire was sent 150 days after the quarantine ended.

Mycophenolic acid interferes the transcriptional regulation and protein trafficking of maturation surface markers in dendritic cells.

Background: The ability of dendritic cells (DCs) to regulate adaptive immunity makes them interesting cells to be used as therapeutic targets modulating alloimmune responses. Mycophenolic acid (MPA) is an immunosuppressor commonly used in transplantation, and its effect on DCs has not been fully investigated.

Methods: Monocyte-derived DCs were obtained from healthy volunteers and cultured for 7 days.

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.

[The cognitive-behavioural impact of hypertension].

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.

Measurement of calcineurin activity in peripheral blood mononuclear cells by ultra-high performance liquid chromatography-tandem mass spectrometry. Renal transplant recipients application (pharmacodynamic monitoring).

Background: Therapeutic drug monitoring of calcineurin inhibitor, tacrolimus (TAC), is routinely used in post-transplantation. Currently, measurement of calcineurin activity has been proposed as a promising clinical tool to evaluate efficacy and to optimize drug dosing. The main aim of our study was to develop a method to measure phosphatase calcineurin activity (CNA) in peripheral blood mononuclear cells (PBMCs) by ultra-high performance liquid chromatography-tandem mass spectrometry and to validate it following FDA and EMA guidelines.

The depressor axis of the renin-angiotensin system and brain disorders: a translational approach.

All the components of the classic renin-angiotensin system (RAS) have been identified in the brain. Today, the RAS is considered to be composed mainly of two axes: the pressor axis, represented by angiotensin (Ang) II/angiotensin-converting enzyme/AT1 receptors, and the depressor and protective one, represented by Ang-(1-7)/ angiotensin-converting enzyme 2/Mas receptors. Although the RAS exerts a pivotal role on electrolyte homeostasis and blood pressure regulation, their components are also implicated in higher brain functions, including cognition, memory, anxiety and depression, and several neurological disorders.

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.

Online Haemodiafiltration Improves Inflammatory State in Dialysis Patients: A Longitudinal Study.

Background: Patients undergoing conventional hemodialysis (C-HD) present a greater immuno-inflammatory state probably related to uremia, sympathetic nervous system (SNS) activation and /or membrane bioincompatibility, which could improve with a technique-switching to online hemodiafiltration (OL-HD). The antigen-independent pathway activation of this modified immunologic state turns dendritic cells (DC) into an accurate cell model to study these patients. The aim of this study is to further evaluate the immune-inflammatory state of patients in C-HD assessed by DC maturation.

Association Between Hypertension, Menopause, and Cognition in Women.

The aim of this study was to investigate the cognitive state in women and its relation to menopause and hypertension (HTN). The authors included 1034 women aged 47.13±15.

At the Heart of Brain Disorders - Preventing Cognitive Decline and Dementia.

Vascular risk factors are shared by heart and brain. Vascular brain injury (small vessel disease, stroke) alone or combined with neurodegenerative pathology (β-amyloid depositions) brings about either cognitive decline and vascular dementia or Alzheimer's disease. Long-term exposure to vascular risk factors precedes the onset of neurocognitive diseases by one or two decades.

Induction of suppressive allogeneic regulatory T cells via rabbit antithymocyte polyclonal globulin during homeostatic proliferation in rat kidney transplantation.

Experimental studies have shown that rabbit antithymocyte polyclonal globulin (ATG) can expand human CD4+CD25++Foxp3+ cells (Tregs). We investigated the major biological effects of a self-manufactured rabbit polyclonal anti-rat thymoglobulin (rATG) in vitro, as well as its effects on different peripheral T-cell subsets. Moreover, we evaluated the allogeneic suppressive capacity of rATG-induced Tregs in an experimental rat renal transplant model.

Optimal sparse sampling for estimating ganciclovir/valganciclovir AUC in solid organ transplant patients using NONMEN.

Background: Ganciclovir and valganciclovir (GCV/VGCV) are used for the treatment and prophylaxis of cytomegalovirus in solid organ transplant (SOT) patients. An area under the time-concentration curve of 40-50 μg × h/mL is related to efficacy. Therapeutic drug monitoring could prevent suboptimal drug exposure and adverse events, but obtaining full concentration profiles is not feasible.

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).

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).

Cognition and vascular risk factors: an epidemiological study.

We conducted an epidemiological approach to identify the negative impact of the vascular risk factors (such as hypertension, diabetes and hypercholesterolemia) over cognition. The interesting aspect of this study was that the survey was conducted in all age groups through a voluntary call (n = 1365; ≥18 years old, both sexes; age 49 ± 15 y, female 75.7%).

Impact of small molecules immunosuppressants on P-glycoprotein activity and T-cell function.

Purpose: P-glycoprotein (Pgp) is a member of the ABC-transporter family that transports substances across cellular membranes acting as an efflux pump extruding drugs out of the cells. Pgp plays a key role on the pharmacokinetics of several drugs. Herein, we have studied the effects of immunosuppressants on Pgp function, assessing rhodamine-123 (Rho123) uptake and efflux in different T-cell subsets.

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.

Cognitive evolution in hypertensive patients: a six-year follow-up.

Background: Several studies have examined the links between hypertension, vascular damage, and cognitive impairment. The functions most commonly involved seem to be those associated with memory and executive function.

Aims: 1) to report the cognitive evolution in a cohort of hypertensive patients, 2) to identify the affected domains, and 3) to correlate the results obtained with blood pressure measurements.