Often the language needed to communicate these sensations seems inadequate. Yet, interoceptive sensations may be critical for survival. pH might be one of a variety of signals that could produce interoceptive sensations by activating pH-sensitive receptors in the brain to evoke adaptive responses. The survival value of rapidly detecting CO2 to prevent suffocation seems clear. Nearly 20 years ago Donald Klein drew from this observation Inhibitors,research,lifescience,medical to hypothesize that the suffocation detection system might be falsely triggered to produce panic attacks.5 Conceivably, heightened pH sensitivity could constitute

such a false alarm. Summary We don’t yet know why panic attacks occur. Nor do we completely understand why those who suffer panic attacks are hypersensitive to panicogens. However, the potential ability of CO2 and lactate, the two most well-studied panicogens, to alter brain pH suggests that pH chemosensation could be instrumental. Acid-sensitive molecules are widely distributed in Inhibitors,research,lifescience,medical fear circuit structures and elsewhere in the brain. Consistent with this observation, a variety of brain sites have been implicated in pH chemosensation including brain stem respiratory nuclei, midbrain raphe neurons, hypothalamus, and amygdala. Inhibitors,research,lifescience,medical However, a number of questions

remain. For example, what specific role(s) do each of these pH-sensitive sites and pH-sensitive molecules play? Could there be additional sources of acidosis and pH fluctuation besides CO2 or lactate that might activate these chemosensory pathways? Finally, might genetic or epigenetic variability in chemosensation lead to panic disorder or other psychiatric and neurological illnesses? That we are now in a position Inhibitors,research,lifescience,medical to ask these questions is in itself a significant advance. As we continue to learn more about CO2 and pH chemosensation in the brain, the answers to these questions may be within

reach. Moreover, an improved understanding of pH signaling and dysregulation might very Inhibitors,research,lifescience,medical well lead to an entirely new avenue of therapeutic intervention. Acknowledgments The selleck kinase inhibitor author thanks Drs Michael Welsh, George Richerson, Margaret Price, William Coryell, Jess Fiedorowicz, and Tom Brashers-Krug for discussions and helpful comments. Dr Wemmie’s work is supported by NIMH 1R01MH085724-01, NINDS 1R01NS0641 59-01 A109, Department of Veteran’s Affairs Merit Review Program, McKnight Endowment Fund for Neuroscience, and the DANA Foundation.
In recent years, the development of neuroimaging techniques such as high-resolution next magnetic resonance imaging (MRI), functional magnetic resonance imaging (fMRI), positron emission tomography (PET), or single photon emission tomography (SPECT) has promoted the identification of structural and functional characteristics underlying mental disorders to a great extent. In anxiety disorders, recent neuroimaging techniques have contributed greatly to diagnosis and treatment, and helped to shed light on the neurobiological basis of anxiety in general.

Dried fruit of M. fragrans and the barks of C. verum were grounded, and the powdered materials were hydrodistilled into steam distillation apparatus, as mentioned above. Isolated volatile oil extracts

collected from each distillation process were added to each other and dried over anhydrous sodium sulphate and stored in dark glass bottles in a fridge at 4°C until use. Macrophage Infection Healthy human macrophage cells were collected and cultured in RPMI. medium supplemented with 10% heat-inactivated fetal calf serum. For macrophage growth assays, 96-well microtiter Inhibitors,research,lifescience,medical plates were seeded with 2×105 macrophages/well and infected with B. abortus 544 at a ratio of 1:100 bacteria/macrophage. Cells were incubated for one h at 37°C in 5% CO2. Extracellular bacteria were removed by three washes with PBS, Inhibitors,research,lifescience,medical followed by treatment with 25 µg/ml of gentamicin for 30 min. Then, the cells were maintained by the addition of medium containing

5 µg/ml of gentamicin. To evaluate the effect of plants volatile oil extracts on the ability of Brucella to invade human macrophage, 1% concentration of the five studied volatile oil extracts, or 0.1% of C. verum plus 1% of the other four volatile oil extracts, were added after 2, 4, 24, 48, 72, 96, 120 and 144 h of infection, the cells were Inhibitors,research,lifescience,medical washed three times by PBS, and lysed with 0.1% Triton. Five minutes after the this website incubation at room temperature, the lysates were plated on 2YT agar and incubated at 37°C for 48 h; in order to determine the intracellular bacterial count. All experiments were performed in triplicate. Macrophages infected with B. abortus 544 at a ratio of one bacteria/100 macrophage without adding any oil extract as a control. Statistical Methods Inhibitors,research,lifescience,medical Antibacterial properties of oil extracts were analyzed with one-way repeated Inhibitors,research,lifescience,medical measures analysis of variance (ANOVA) fallowed by Tukey’s multiple comparison test to compare the difference between each pair of means. Data were transformed into log10 CFU prior to analysis to homogenize the variance. All analyses

were conducted by using GraphPad Prism Statistical Software V5.03. Differences were considered statistically significant at P<0.05. Results Brucella abortus 544 log10 counts in human macrophages were significantly suppressed (F5,35=22.7; P<0.0001) by volatile oil extracts treatments compared with the L-NAME HCl untreated control. For example, the inhibitory effect of C. verum at a concentration of 1% was started 24 h and continued till 144 h after the infection, and the log10 counts increased only from 3.11 to 4.9. The repeated measures ANOVA followed by Tukey’s test of multiple comparisons revealed that C. verum volatile oil possessed the strongest antibacterial effect compared to all the other essential oil extracts (figure 1). It is worth pointing out that no significant difference occurred between the antibacterial activity of lemon, peppermint, sweet marjoram and nutmeg volatile oil extracts.

Subsequently, the cells were washed with PBS followed by the addition of acidic isopropanol (0.04 M HCl in absolute isopropanol).Then the plates were shacked for one min and the absorbance was recorded at 570 nm using a microplate reader system. Determination of Total Antioxidant Activity of HESA-A The activity of HESA-A against oxidative stresses was measured with an antioxidant assay kit (Sigma Aldrich, USA). The kit provides for an efficient measurement of the total antioxidant activity. For the evaluation of

the antioxidant property, different concentrations of HESA-A (20-100 µg/ml) were added to 96 well plates, and the antioxidant capacity was evaluated according to the kit manufacture’s protocol. Inhibitors,research,lifescience,medical The CHO and HEK293T cells were grown in 96 well plates. Then, Inhibitors,research,lifescience,medical various concentrations of HESA-A (100-800 ng/ml) were added to the culture medium one hour before H2O2 treatment. Afterwards, CHO cells and HEK293T cells were treated with 16 and 10 mM H2O2, respectively. Finally, the culture medium was collected and antioxidant capacity of HESA-A was measured according to the supplier protocol. Trolox, a water-soluble vitamin E analog, was provided by the kit and was used as a positive control of antioxidant activity. Absorbance was monitored at

405 nm Inhibitors,research,lifescience,medical using a ELx800 Absorbance Microplate Reader. Statistical Analysis The results are expressed as mean ± SD of three independent experiments. Differences between Inhibitors,research,lifescience,medical groups were compared using one-way Analysis of Variance (ANOVA) followed by Tukey-Kramer Multiple Comparison Test. A probability of committing type one error of ≤0.05 was considered statistically significant. Results Cytotoxic Effect of HESA-A on

CHO and HEK293T Cell Lines Different concentrations of HESA-A were used to clarify direct effects of HESA-A on the viability of CHO and HEK293T cells. At first, the cells were exposed to HESA-A (100-1000 ng/ml). As determined by MTT assay, the viability Inhibitors,research,lifescience,medical of the cells incubated with the concentrations of 100 and 200 ng/ml of HESA-A was shown to be about 89% after 90 min, while in the presence of 300 ng/ml or AP24534 purchase higher concentrations of the HESA-A the viability was decreased down to 48% comparing to the controls (figure 1a). This indicates that cytotoxicity of HESA-A is dose dependent. Next, for optimization of Histone demethylase the treatment duration the cells were exposed to 100 and 200 ng/ml HESA-A for one h, 1:30 h, two h and 2:30 h. Then the cytotoxicity was determined by MTT assay. Compared to the control, no changes were observed in the viability of the cells In the presence of 100 and 200 ng/ml of HESA-A. However, the cytotoxic effects of HESA-A at 200 ng/ml were shown to be time dependent (figure 1b). Therefore, the minimal toxic doses of HESA-A were determined. Figure 1 The effects (mean±SD, three replicates) of HESA-A on viability of CHO and HEK293T cells. a) The cells were treated with different concentrations of HESA-A for 1.5 hrs.

9 In addition, variation at TMCO1 has been associated with intraocular pressure, 16 while 9p21 and SIX1/SIX6 are associated with cup-to-disc ratio 17 in normal individuals. We provide evidence for association at SIX1/SIX6, 9p21, and nominally at TMCO1 with incident OAG. Thus, loci associated with advanced glaucoma and relevant biometric traits are also associated with the initial onset of OAG (incidence). Those SNPs discovered in previous cohorts with typical (nonadvanced) OAG are not found to be associated with buy PF-02341066 OAG

incidence in our cohort, although power to detect weaker associations or those at rarer SNPs is limited. The association of sex with incident OAG in the cohort has been previously reported, 11 as has the higher-than-expected level of hypertension in the BMES cohort. 18 and 19 The current cohort was sufficiently DNA Damage inhibitor powered to detect an odds ratio of ∼1.6. This is larger than those observed in the original discovery cohorts of cross-sectional (prevalent OAG) patient recruitment, although significant effects were still observed in this study, suggesting that the SNPs may be more important in predicting disease onset than progression, or that the true effect size is larger than previously

reported. However, larger prospective cohorts will be Modulators needed to properly assess the 8q22 and CAV1/CAV2 loci in particular. A nominal association was observed at TMCO1. This SNP has a lower allele frequency than others in the study (11% in controls) and the finding did not reach significance here in the context of multiple testing, owing to the lower power of this study (∼36%) to detect an effect at the minor allele frequency of 11%. We have previously reported an association of this locus with prevalent OAG in the BMES cohort with odds ratio (OR) = GPX6 1.57, P = .022. 7 The odds ratio for incident OAG reported in the current study was larger (OR = 1.74, P = .013) despite the smaller sample size. We thus conclude that TMCO1 is also confirmed to be associated

with incident OAG. The current study shows that OAG loci that are associated with OAG-relevant ocular parameters (cup-to-disc ratio and intraocular pressure) are specifically associated with OAG incidence independently of other known risk factors. This suggests that these loci are responsible at least in part for the initiation of OAG, consistent with their role in determination of these risk factor traits, which are themselves predictive for OAG development. We show also that the loci specifically associated with advanced glaucoma may also be important in initiation of OAG, and thus could be important in risk stratification among glaucoma suspect and early glaucoma patients.

16,17,32 A priori identification of the patients who will be at a higher risk for development of adverse side effects could help clinicians avoid lengthy ineffective APD trials and limit patients’ exposure to drug side effects. Since the mid-1990s, the field of pharmacogenetics has offered the potential for providing readily accessible, immutable biomarkers – DNA sequence variants – that might Inhibitors,research,lifescience,medical be predictive of an individual’s propensity for both positive and adverse effects of drugs. However, to date, the promise of personalized medicine has remained unfulfilled.

Because academic pharmacogenetic research is often limited to small and clinically heterogeneous samples, individual studies have been unable to provide compelling results. Additionally, the modest effect sizes which are common in complex genetics present an obstacle in the quest for valid biomarkers, which require high sensitivity and specificity for individual BVD-523 chemical structure clinical prediction. Moreover, examination of disparate polymorphisms across a wide variety of candidate Inhibitors,research,lifescience,medical genes has created an impression of scattered, unreplicated findings. Recently, however, a series of findings across multiple

laboratories have begun to converge for a few genes related to serotonin and dopamine, the most prominent Inhibitors,research,lifescience,medical neurotransmitters targeted by APDs. In the subsequent sections, we will focus on the converging evidence implicating the most wellstudied candidates for pharmacogenetic predictors of antipsychotic-induced side effects. Particular emphasis will be placed on single nucleotide polymorphisms (SNPs) that have a sufficient evidence

base to have permitted published meta-analytic studies. Tardive dyskinesia Tardive dyskinesia is the most extensively studied APDinduced side effect in the pharmacogenetics literature to date. These Inhibitors,research,lifescience,medical studies have typically been cross-sectional in nature, with ascertainment based on retrospective identification of cases with varying treatment histories and duration. The ability to study prevalence, rather than incidence in the context of a clinical trial, has permitted cumulative sample sizes in the thousands. It is important to note, however, that this ascertainment Inhibitors,research,lifescience,medical strategy may suffer from false negatives (patients with mild or reversible MycoClean Mycoplasma Removal Kit TD) and false positives (patients with acute motoric abnormalities that do not persist). Within this literature, variants within the genes encoding dopamine D2 and D3 receptors have been the primary focus, as detailed below. Dopamine D2 receptor blockade is a property of all known antipsychotics, as demonstrated in vitro and in vivo,34 yet a predictive relationship between variation in the DRD2 gene (located on chromosome 11q22) and APD-induced side effects has only been examined in a handful of studies. Most pharmacogenetic studies to date have examined the 3′ Taq1A polymorphism (rs1800497), which more recently has been determined to be a nonsynonymous coding SNP in a neighboring ankyrin repeat gene (ANKK1 Glu713Lys).

Bruniquel and Schwartz122 found that a region in a promoter of the IL-2 gene demethylates following activation in the absence of DNA replication and results in a profound increase in the production of IL-2. These two papers MLN0128 in vitro provide the initial evidence for an active, environmentally driven alteration in DNA methylation in postmitotic cells. Szyf and colleagues101,123 Inhibitors,research,lifescience,medical first proposed that DNA methylation is enzymatically reversible and that DNA methylation is dynamic in fully differentiated cells. This idea remains controversial. Active demethylation was nevertheless clearly demonstrated early in embryogenesis and the parental

genome undergoes replication independent, active demethylation hours after fertilization, well before the initiation of replication. Demethylation at

very early stages in development has Inhibitors,research,lifescience,medical been relatively accepted, but the possibility of postnatal demethylation, especially in fully differentiated somatic cells, has been hotly disputed. However, active replication demethylation was demonstrated in Epstein-Barr virus (EB V)-infected B cells and in HEK293 cells. The HEK293 studies suggest Inhibitors,research,lifescience,medical that active replication-independent demethylation takes place in differentiated somatic cells and that it is dependent on alterations in chromatin structure. Earlier studies from Szyf’s122 laboratory extracted active DNA demethylase activity from a human lung cancer cell line and identified a protein with demethylase activity, which was cloned concurrently Inhibitors,research,lifescience,medical by Bird’s group and named MBD2.123 Interestingly, the protein, MBD2, was found by Bird’s group and others to also associate with a chromatin remodeling complex containing HDAC, which is involved in silencing Inhibitors,research,lifescience,medical of gene expression through the recruitment of a repressor complex. The assignment of a demethylase function to a protein that was independently discovered as a recruiter of repressor complexes triggered the expected controversy in the field and reports that MBD2 failed to produce demethylase activity. However, the observation that MBD2/demethylase Thymidine kinase expression

produces the demethylation of some, but not all, promoters in a dose- and time-dependent manner has been confirmed.108,124 Clearly, the contextual factors that determine MBD2 demethylase activity remain to be fully explained. Interestingly, MBD2 increased gene expression in those instances where promoter demethylation occurred, suggesting that not all promoters respond in the same orderly manner. Indeed, the same is true for DNA methylation, which impedes the DNA binding of most, but not all transcription factors; SP1 binds to methylated DNA. Antisense knock down of MBD2 resulted in inhibition of active demethylation induced by valproate and caused hypermethylation and silencing of the prometastatic gene uPA in metastatic breast cancer cells.

For example, in an extensive nursing home study, Cohen-Mansfield and collaborators found that a large number of patients with verbal aggression had undiagnosed hip fractures.9

Furthermore, an evaluation of the correlation between behaviors such as verbal aggression and environmental factors shows that the quality of the patient’s social environment is inversely proportional to the presence of verbal aggression. This suggests that an improvement in social interactions can have a therapeutic effect on verbal aggression. Indeed, a study by the same group of researchers shows intervention based on increasing social interaction to be better than a control intervention in the treatment of verbal Inhibitors,research,lifescience,medical aggression.8 Based on the aforementioned example, we believe that behavioral Inhibitors,research,lifescience,medical and environmental interventions should play a key role in the management of BPSD, thereby challenging clinicians and researchers to develop new and creative interventions.21 Conclusion Although the etiology of BPSD remains unknown, available evidence suggests that a combination of behaviorspecific biological and environmental factors may be partially responsible for

the onset of BPSD. Diagnosis The diagnosis of BPSD is based on direct clinical history, direct observation, psychiatric and physical examinations, and reports by care providers. In addition, laboratory tests are Inhibitors,research,lifescience,medical used to evaluate the presence of medical conditions that can trigger or exacerbate the clinical presentation of BPSD. The clinical characteristics of BPSD are syndrome-specific. Inhibitors,research,lifescience,medical The following is a brief description of some of the most, commonly observed syndromes. Psychosis

The symptoms of psychosis are defined by the presence of hallucinations and delusions lasting for one or more months. The onset of psychotic symptoms must occur after the onset of the dementia in order to fit this diagnosis. The main differential diagnosis Inhibitors,research,lifescience,medical is with late-onset schizophrenia; however, symptom presentation of BPSD psychosis is substantially different from schizophrenia. Symptoms such as misidentification of caregivers and visual hallucinations are common no in BPSD psychosis and are rare in patients with schizophrenia. In contrast, patients with selleck chemical schizophrenia usuallypresent Schneiderian first-rank symptoms, bizarre complex delusions, and active suicidal ideation. These symptoms are rarely observed in BPSD psychosis. Disease progression is also reported to be substantially different in BPSD psychosis. Psychosis in schizophrenia rarely shows remission, and the need for antipsychotic treatment is prolonged; psychosis in BPSD has a shorter duration and therefore requires shorter periods of treatment. Circadian rhythm (sleep-wake) disturbance in dementia Circadian rhythm disturbances among BPSD patients, termed sleep-wake rhythm disturbances for the purposed of this paper, make caregiving extremely difficult and are among the most, important reasons for institutionalization.

The reports from these second and third generations were so astonishing that many considered the

“historic” standard of CHOP to be Ibrutinib unethical. An editorial in the Annals of Internal Medicine in 1985 concluded that “the results of second- and third-generation chemotherapy regimens are so consistently good from so many independent sources, that they continue to engender even more ferment in the treatment of large cell lymphoma.”4 Table 1 Phase II data—diffuse large cell lymphoma. Against this general background, in the late Inhibitors,research,lifescience,medical 1980s, the Southwest Oncology Group and the Eastern Oncology Group in the US initiated a prospective randomized phase III trial comparing the standard CHOP regimen with three intensive chemotherapy regimens for advanced lymphomas. The results published in the New England Journal of Medicine in 1993 astounded the hematology community with similar overall survival for all regimens and with no subgroup of patients in which Inhibitors,research,lifescience,medical survival was improved by a third-generation regimen (Figure 1).5 Furthermore, the CHOP regimen was less toxic, thus concluding that

CHOP remained the best available treatment for patients with advanced-stage intermediate- or high-grade lymphomas. These remarkable Inhibitors,research,lifescience,medical results highlighted the difficulty of interpreting limited phase II data due to inherent selection biases. To this day CHOP remains the standard of care for aggressive lymphomas and is the yard-stick against which Inhibitors,research,lifescience,medical all new advances are compared. The only proven advance in the management of lymphoma has been the addition of rituximab which was established through a carefully controlled phase

III study where CHOP alone was the comparator arm.6 Figure 1 Overall survival of CHOP regimen Inhibitors,research,lifescience,medical prospectively compared with three third-generation regimens. Relapsed Aggressive Lymphoma Another example relates to the management of relapsed aggressive lymphomas. Early data in the 1980s suggested that the results from autologous transplantation were far superior to the use of traditional conventional chemotherapy, which in fact yielded almost no cures for the disease. Nevertheless, given the lessons learned from the phase III study of CHOP, some Endonuclease skepticism existed in the hematologic community, and the need for a prospective phase III study was clearly apparent. The PARMA study (Figure 2) was designed specifically for this purpose in 1987. Recruitment was difficult due to a reluctance by many practitioners to offer standard chemotherapy to even those with the better prognosis among the relapsed groups. Preliminary data, presented at international meetings in 1992 and 1993 (Figure 3), were widely interpreted as demonstrating that high-dose therapy with autologous transplantation did not provide a significant improvement.

As a consequence, resection of EHD from a colorectal primary has increasingly become accepted over the last decade. We herein review the management of patients with EHD metastatic disease from a colorectal primary tumor. Specifically, we highlight

the data on the surgical management of patients with metastatic disease at the most common EHD sites (e.g. lung, hilar/Rigosertib mw peri-hepatic lymph nodes, peritoneum), as well as define general oncological principles for treating this challenging cohort of patients. CRC Metastasis: Implication of Number and Anatomic Site There has been controversy regarding the relative importance of Inhibitors,research,lifescience,medical total number of EHD metastatic tumors versus location of the specific metastatic site (23,24,26). Some investigators have suggested that the total number of metastatic lesions is the dominant factor that predicts outcome following surgical resection (24,26). Inhibitors,research,lifescience,medical In a provocative paper by Elias et al., the authors argued that the site of the metastatic disease did not matter – only the number of metastatic lesions (26). In this study, the total number of tumors impacted survival, but the location of the metastatic disease did not. However, data from this study were difficult to interpret due to the small

number of patients included in each subset analysis. More recently, our group published a large, international series looking at resection of extra-hepatic Inhibitors,research,lifescience,medical CRC metastases (8). In this study, both the total number of metastases and the location of the metastatic disease were associated with prognosis. Survival was strongly associated with overall tumor burden (Figure 1). We noted, however, that among patients with a large tumor burden (>6 metastatic lesions) the relative Inhibitors,research,lifescience,medical prognostic impact of anatomic location was less (Figure 2). Of note, among patients with a lower

burden of disease, anatomic location of the metastatic disease had a strong influence on survival (Table 1). As such, both total number of EHD metastases and the location of the metastases should be considered when assessing patients for Inhibitors,research,lifescience,medical surgery. Figure 1 A: Overall survival among patients with colorectal liver metastasis (CLM) only stratified by number of CLM treated; B: Overall survival among patients with CLM + extrahepatic disease (EHD) stratified by number of CLM + EHD metastasis treated. Used with … Figure 2 Overall survival tuclazepam rates when the total number of metastases (CLM + EHD) was (A) 1-3 (B) 4-6 (C) >6 stratified by the presence or absence of EHD. Used with permission: Pulitano C, Bodingbauer M, Aldrighetti L, et al. Liver resection for colorectal … Table 1 Survival statistics by location of extrahepatic disease. Used with permission: Pulitano C, Bodingbauer M, Aldrighetti L, et al. Colorectal Liver Metastasis in the Setting of Lymph Node Metastasis: Defining the Benefit of Surgical Resection. Annals of … Pulmonary Metastasis The lung is one of the most common metastatic sites for colorectal carcinoma.

Parmi les HTA non contrôlées, il est décrit des sujets ayant une HTA résistante à une prise LY2109761 purchase en charge usuelle. Améliorer la prise en charge des hypertensions résistantes est justifiée par l’observation d’une augmentation de la prévalence d’atteinte des organes cibles et de l’incidence des AVC de près de 50 % sur une période de 3,8 ans par rapport aux patients dont l’HTA est bien contrôlée. Pour améliorer la prise en charge de l’HTA résistante, la Société française d’HTA, filiale de la Société

française de cardiologie publie onze recommandations dont l’objectif principal est de permettre d’apporter des informations actualisées ayant la meilleure justification scientifique et qui soient applicables dans la pratique quotidienne des professionnels de santé travaillant dans le système de santé français. Le souhait de réaliser un document synthétique a conduit à limiter le nombre ZVADFMK des recommandations. Pour permettre un usage facilité de ces recommandations par le médecin généraliste et le médecin spécialiste, les étapes de la prise en charge sont résumées sur les Figure 1 and Figure 2. Afin de favoriser la lecture du texte argumentaire, celui-ci a été volontairement réduit mais est disponible sur www.sfhta.eu. Pour la réalisation de cette recommandation,

les règles suivantes ont été appliquées : • effectuer une recherche bibliographique ayant pour mots clés : « resistant hypertension, treatment-resistant hypertension, resistant hypertension review » ; Il est recommandé de définir une HTA résistante comme une HTA non contrôlée en consultation (PA ≥ 140/90 mmHg

chez un sujet de moins de 80 ans, ou PAS ≥ 150 mmHg chez un sujet de plus de 80 ans) et confirmée par une mesure en dehors du cabinet médical (automesure ou mesure ambulatoire de la pression artérielle), malgré une stratégie thérapeutique comprenant des règles hygiéno-diététiques adaptées et une trithérapie antihypertensive, Org 27569 depuis au moins 4 Libraries semaines, à dose optimale, incluant un diurétique. Les sociétés savantes internationales et les organismes assurant la rédaction de recommandations professionnelles ont déjà édictés des recommandations ayant pour thème la prise en charge des hypertensions résistantes. Pour définir la population de patients sur laquelle s’applique ces recommandations, il est usuellement retenu les patients hypertendus traités dont la pression artérielle (PA) en consultation est supérieure à l’objectif tensionnel malgré une trithérapie antihypertensive à dose optimale (AHA recommandation 2013) [4], ou ceux dont la PA est supérieure à 140/90 mmHg malgré une stratégie thérapeutique incluant une modification appropriée du mode de vie et une trithérapie incluant un diurétique et deux autres classes d’antihypertenseur à dose adéquate (ESC/ESH recommandation 2013) [5].