Comparative assessment of CacyBP/SIP, ß-catenin and cannabinoid receptors in the adrenals of hypertensive rats.

Taking into account homeostatic disorders resulting from arterial hypertension and the key importance of CacyBP/SIP, ß-catenin and endocannabinoids in the functioning of many organs, it was decided to assess the presence and distribution of CacyBP/SIP, ß-catenin, CB1 and CB2 in the adrenal glands of hypertensive rats of various aetiology. The study was conducted on the adrenal glands of rats with spontaneous and renovascular hypertension. The expression of CacyBP/SIP, ß-catenin, CB1 and CB2 was detected by immunohistochemistry and real-time PCR method. The results of the present study revealed both lower gene expression and immunoreactivity of CacyBP/SIP in the adrenal glands of all hypertensive groups compared to the normotensive rats. This study demonstrated a reduction in the immunoreactivity and expression of the ß-catenin, CB1 and CB2 genes in the adrenals of 2K1C rats. While in SHR, the reaction showing ß-catenin and CB1 was very weak or negative, and the expression of CB2 in the adrenal glands of these rats increased. The results of this study show, for the first time, marked differences in the expression of CacyBP/SIP, ß-catenin and CB1 and CB2 cannabinoid receptors in the adrenal glands of rats with primary (SHR) and secondary hypertension (2K1C).

Assessment of mild autonomous cortisol secretion among incidentally discovered adrenal masses.

Incidentally discovered adrenal masses are common and mostly benign and non-functioning adenomas. However, evolving evidence suggests that a notable proportion of these adrenal adenomas may demonstrate mild autonomous cortisol secretion (MACS), which has been associated with an increased risk for hypertension, hyperglycemia, obesity, dyslipidemia, vertebral fractures, adverse cardiovascular events, and mortality. Therefore, it is advised that all patients with an incidentally discovered adrenal mass be tested for MACS. When there is convincing evidence for MACS, surgical adrenalectomy has been associated with an improvement in certain metabolic parameters and a reduction in vertebral fractures; however, conclusive evidence demonstrating decreased cardiovascular outcomes or mortality are not yet available. Future studies with adequate randomization and follow-up to assess adverse clinical endpoints are needed to determine the optimal management and follow-up of patients with MACS.

Characterization of dietary patterns and assessment of their relationships with metabolomic profiles: A community-based study.

BACKGROUND & AIMS: Determining dietary patterns in China is challenging due to lack of external validation and objective measurements. We aimed to characterize dietary patterns in a community-based population and to validate these patterns using external validation cohort and metabolomic profiles. DESIGN: We studied 5145 participants, aged 18-80 years, from two districts of Hangzhou, China. We used one district as the discovery cohort (N = 2521) and the other as the external validation cohort (N = 2624). We identified dietary patterns using a k-means clustering. Associations between dietary patterns and metabolic conditions were analyzed using adjusted logistic models. We assessed relationships between metabolomic profile and dietary patterns in 214 participants with metabolomics data. RESULTS: We identified three dietary patterns: the traditional (rice-based), the mixed (rich in dairy products, eggs, nuts, etc.), and the high-alcohol diets. Relative to the traditional diet, the mixed (ORadj = 1.7, CI 1.3-2.4) and the high-alcohol diets (ORadj = 1.9, CI 1.3-2.7) were associated with type 2 diabetes and hypertension, respectively. Similar results were confirmed in the external validation cohort. In addition, we also identified 18 and 22 metabolites that could distinguish the mixed (error rate = 12%; AUC = 96%) and traditional diets (error rate = 19%; AUC = 88%) from the high-alcohol diet. CONCLUSIONS: Despite the complexity of Chinese diet, identifying dietary patterns helps distinguish groups of individuals with high risk of metabolic diseases, which can also be validated by external population and metabolomic profiles.

Pericardial adiposity versus body adiposity measured by BMI in the assessment of coronary atherosclerosis burden in patients with hypertension.

OBJECTIVES: The link between obesity and hypertension with coronary atherosclerosis is complex. We aimed to assess the association of cardiac fat deposition measured by pericardial fat volume(PFV) using by multi-detector CT(MDCT) and general obesity measured by BMI with subclinical coronary atherosclerotic markers (coronary artery calcium score (CAC), coronary plaque and stenosis) in patients with hypertension and suspected coronary artery disease. METHODS: Among 496 patients presenting with chest pain who underwent 64-slice MDCT angiography to exclude occlusive coronary disease, 261 patients with hypertension (age: 57 ± 8 years, 45% males) enrolled in the present study. RESULTS: PFV showed a significant association with CAC(r = 0.2,P = .001),coronary stenosis severity(PFV median(IQR) 88(63-161) in patients with coronary stenosis<50% compared to PFV median(IQR) 125(85-140) in patients with coronary stenosis ≥ 50%, P = .001) and coronary plaque presence (PFV median (IQR) 89(65-128) in patients without plaque compared to PFV median (IQR) 115(74-150) in patients with plaque presence = 0.03).the significant association of PFV with CAC[odds ratio(95% confidence interval = 0.5(0.19-0.97),P = .001] and coronary stenosis severity [odds ratio(95% confidence interval = 1.1(1.00-1.01),P = .01]persisted after adjustment for conventional cardiac risk. BMI showed a significant association with significant coronary stenosis presence (P = .02).The association of BMI with significant coronary stenosis presence after adjustment for conventional cardiac risk factors (P = .03).BMI showed no significant association with CAC and coronary plaque presence (P > .05). CONCLUSION: PFV showed a significant independent association with coronary calcification and significant coronary stenosis in patients with hypertension rather than BMI.

COVID-19 and renin-angiotensin system modulators: what do we know so far?

INTRODUCTION: The novel coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory system-coronavirus-2 (SARS-CoV-2), is an important medical problem worldwide. Increased risk of mortality has been reported in patients with cardiovascular disease, such as hypertension (HTN). SARS-CoV-2 invades the pulmonary alveolar epithelial cells by binding to the surface receptor, angiotensin-converting enzyme 2 (ACE2). Renin-angiotensin system (RAS) modulators can increase levels of ACE2. Thus, concerns have been raised regarding an increased risk of severe COVID-19 infection in patients receiving RAS antagonists. AREAS COVERED: We reviewed current literature about the potential association between the utilization of RAS inhibitors, namely angiotensin-converting enzyme inhibitors (ACE-inhibitors) and angiotensin-receptor blockers (ARBs) and likelihood of developing severe COVID-19 infection and whether or not continuation of these medications is appropriate in patients with active disease. EXPERT OPINION: The joint statement from the American College of Cardiology (ACC), American Heart Association (AHA), European Society of Cardiology (ESC) and Heart Failure Society of America (HFSA), strongly recommends that physicians should not initiate or withdraw their usual RAS-related treatments (ACE-inhibitor/ARB) to COVID-19 infected patients with cardiovascular disease. The decision should be made based upon each patient's clinical presentation and hemodynamic status.

Comprehensive assessment of mitochondrial respiratory function in freshly isolated nephron segments.

Changes in mitochondrial function are central to many forms of kidney disease, including acute injury, diabetic nephropathy, hypertension, and chronic kidney diseases. As such, there is an increasing need for reliable and fast methods for assessing mitochondrial respiratory function in renal cells. Despite being indispensable for many mechanistic studies, cultured cells or isolated mitochondria, however, often do not recapitulate in vivo or close to in vivo situations. Cultured and/or immortalized cells often change their bioenergetic profile and phenotype compared with in vivo or ex vivo situations, and isolated mitochondria are simply removed from their cellular milieu. This is especially important for extremely complex organs such as the kidney. Here, we report the development and validation of a new approach for the rapid assessment of mitochondrial oxygen consumption on freshly isolated glomeruli or proximal tubular fragments using Agilent SeaHorse XFe24 and XF96 Extracellular Flux Analyzers. We validated the technique in several healthy and diseased rodent models: the C57BL/6J mouse, the diabetic db/db mouse and matching db/+ control mouse, and the Dahl salt-sensitive rat. We compared the data to respiration from isolated mitochondria. The method can be adapted and used for the rapid assessment of mitochondrial oxygen consumption from any rodent model of the investigator's choice. The isolation methods presented here ensure viable and functional proximal tubular fragments and glomeruli, with a preserved cellular environment for studying mitochondrial function within the context of their surroundings and interactions.

Reactivity of salivary uric acid in response to social evaluative stress in African Americans.

High uric acid (UA) is associated with hypertension and cardiovascular disease (CVD), both of which occur disproportionately among African Americans. High UA also predicts greater blood pressure reactivity responses to acute social stress. However, whether UA itself shows reactivity in response to stress is unknown. We evaluated salivary uric acid (sUA) and blood pressure reactivity in response to acute social stress. Healthy African Americans (N = 103; 32 % male; M age = 31.36 years), completed the Trier Social Stress Test. sUA and blood pressure measurements were taken before, during and after the stressor task. sUA showed significant reactivity and recovery, especially among older African Americans. Total sUA activation was also associated with systolic and diastolic blood pressure total activation. Findings illuminate that acute stress may be a way in which UA is implicated in hypertension and CVD, suggesting a critical need to explore UA reactivity as a novel parameter of the acute stress response.

Molecular mechanisms of posaconazole- and itraconazole-induced pseudohyperaldosteronism and assessment of other systemically used azole antifungals.

Recent reports described cases of severe hypertension and hypokalemia accompanied by low renin and aldosterone levels during antifungal therapy with posaconazole and itraconazole. These conditions represent characteristics of secondary endocrine hypertension caused by mineralocorticoid excess. Different mechanisms can cause mineralocorticoid excess, including inhibition of the adrenal steroidogenic enzymes CYP17A1 and CYP11B1, inhibition of the peripheral cortisol oxidizing enzyme 11ß-hydroxysteroid dehydrogenase type 2 (11ß-HSD2) or direct activation of the mineralocorticoid receptor (MR). Compared to previous experiments revealing a threefold more potent inhibition of 11ß-HSD2 by itraconazole than with posaconazole, the current study found sevenfold stronger CYP11B1 inhibition by posaconazole over itraconazole. Both compounds most potently inhibited CYP11B2. The major pharmacologically active itraconazole metabolite hydroxyitraconazole (OHI) resembled the effects of itraconazole but was considerably less active. Molecular modeling calculations assessed the binding of posaconazole, itraconazole and OHI to 11ß-HSD2 and the relevant CYP enzymes, and predicted important interactions not formed by the other systemically used azole antifungals, thus providing an initial explanation for the observed inhibitory activities. Together with available clinical observations, the presented data suggest that itraconazole primarily causes pseudohyperaldosteronism through cortisol-induced MR activation due to 11ß-HSD2 inhibition, and posaconazole by CYP11B1 inhibition and accumulation of the mineralocorticoids 11-deoxycorticosterone and 11-deoxycortisol because of hypothalamus-pituitary-adrenal axis (HPA) feedback activation. Therapeutic drug monitoring and introduction of upper plasma target levels may help preventing the occurrence of drug-induced hypertension and hypokalemia. Furthermore, the systemically used azole antifungals voriconazole, isavuconazole and fluconazole did not affect any of the mineralocorticoid excess targets, offering alternative therapeutic options.

Gender Differences in Hypertension.

Hypertension is the leading risk factor for global mortality and morbidity and remains the major preventable cause of cardiovascular diseases. Gender differences in risk factors and awareness, treatment, and control of hypertension have been well established in humans. There are significant differences in epidemiology and clinical characteristic of hypertension between men and women. Moreover, gender differences are linked with several specific types of hypertension, including postmenopausal hypertension, white coat hypertension, masked hypertension, and hypertensive disorders of pregnancy. Gender differences have been implicated in the prevalence and determinants of hypertension and prehypertension whereas the control rate is similar between men and women taking antihypertensive medication. Importantly, distinct roles of the angiotensin-converting enzyme 2/Apelin signaling, sex hormone, endothelin-1, and sympathetic nervous activity contribute to sex differences in blood pressure control. This review summarizes gender differences in clinical features and determinants of hypertension and the underlying mechanisms responsible for hypertension.

[Assessment for antihypertensive drug intake: How, where and when?] / Pourquoi, comment et où dose-t-on les antihypertenseurs en 2019 ?

AIM: Hypertension is a public health problem managed according to therapeutic strategies published in France by the Hauteautoritéde santé (HAS - French Health Authorities). For patients with resistant hypertension, related or not to a non-adherence, prescribers need to be sure the exposure is high enough to achieve the tensional target. Quantitative analysis of antihypertensive drugs in different biological matrices (blood/urine) is one possible solution. However, this involves determining the concentrations observed at standard doses and knowing how to interpret the measured concentrations. It is also necessary to identify medical laboratories that can assay antihypertensive drugs. This was the aim of our work. METHODS: The main antihypertensive drugs recommended by the HAS have been listed. For each of them, we looked for published steady-state plasma/serum concentrations and quantities excreted in the urine at usual dosages. In addition, the elimination half-life and linear pharmacokinetic profile were specified for each antihypertensive agent measured in plasma/serum. Pharmacology-Toxicology laboratories in France likely to carry out assays were identified. The time taken to report the result and the cost of the analysis were also specified. RESULTS: All of the afore-mentioned information has been collected and presented in a table. This can then be used to compare the plasma/serum concentration or the quantity measured in a patient's urine with the values reported in the literature. In cases where the blood sampling times differ between those of the patient and the published data, the patient's measured value is compared to the estimated value based on the published concentrations and pharmacokinetics. CONCLUSION: Interpretation of the plasma/serum/urinary value measured or estimated for an antihypertensive drug is a particularly interesting approach to determine if drug exposure is enough and a possible non-adherence. However, this activity is mostly carried out in hospital centres.

The Association Between Six Surrogate Insulin Resistance Indexes and Hypertension: A Population-Based Study.

Background: The relationship between insulin resistance and hypertension is well established, but the association of different surrogate insulin resistance indexes with the presence of hypertension is still under debate. The aim of this study was to compare the strength of the association between the presence of hypertension and six indexes: triglyceride/HDL cholesterol ratio (TG/HDL-C), Triglyceride Glucose (TyG) Index, Visceral adiposity index (VAI), Lipid accumulation product (LAP), TyG-Body mass index (TyG-BMI), and TyG-Waist circumference (TyG-WC). Methods: Data from a cross-sectional epidemiological study enrolling a sample representative for the Romanian population aged 18-80 years, excluding those with diabetes or requiring treatment for hypertriglyceridemia, were used to calculate the six indexes. The association with the presence of hypertension was examined with binomial and multinomial logistic regression. Results: In multinomial logistic models, which included age, gender, smoking, drinking, sedentary lifestyle, estimated glomerular filtration rate, urinary sodium, urinary albumin creatinine ratio, and use of medications known to influence insulin resistance as covariates, all individual components and surrogate insulin resistance indexes were independently associated with the presence of hypertension. Values of pseudo R square ranged from 0.342 for the multivariate model including TG/HDL-C to 0.357 for the model including TyG-WC, but with no clear superiority of any of the tested indexes over all others. Models including BMI and WC had a similar ability to predict the presence of hypertension as most of the surrogate indexes and they were slightly superior to TG/HDL-C and TyG. Conclusions: Although TG/HDL-C, VAI, LAP, TyG, TyG-BMI, and TyG-WC were independently associated with the presence of hypertension, no superiority could be demonstrated over the use of BMI and WC as predictors of hypertension in this cross-sectional study.

Physical Exercise and Regulation of Intracellular Calcium in Cardiomyocytes of Hypertensive Rats / Exercício Físico e Regulação de Cálcio Intracelular em Cardiomiócitos de Ratos Hipertensos

Abstract Background: Regulation of intracellular calcium (Ca2+) in cardiomyocytes is altered by hypertension; and aerobic exercise brings benefits to hypertensive individuals. Objective: To verify the effects of aerobic exercise training on contractility and intracellular calcium (Ca2+) transients of cardiomyocytes and on the expression of microRNA 214 (miR-214) in the left ventricle of spontaneously hypertensive rats (SHR). Methods: SHR and normotensive Wistar rats of 16 weeks were divided into 4 groups -sedentary hypertensive (SH); trained hypertensive (TH); sedentary normotensive (SN); and trained normotensive (TN). Animals of the TH and TN groups were subjected to treadmill running program, 5 days/week, 1 hour/day at 60-70% of maximum running velocity for 8 weeks. We adopted a p ≤ 0.05 as significance level for all comparisons. Results: Exercise training reduced systolic arterial pressure in hypertensive rats. In normotensive rats, exercise training reduced the time to 50% cell relaxation and the time to peak contraction and increased the time to 50% decay of the intracellular Ca2+ transients. In SHR, exercise increased the amplitude and reduced the time to 50% decay of Ca2+ transients. Exercise training increased the expression of miR-214 in hypertensive rats only. Conclusion: The aerobic training applied in this study increased the availability of intracellular Ca2+ and accelerated the sequestration of these ions in left ventricular myocytes of hypertensive rats, despite increased expression of miR-214 and maintenance of cell contractility.

Resumo Fundamento: A regulação intracelular de cálcio (Ca2+) em cardiomiócitos é alterada pela hipertensão, e o exercício físico aeróbico traz benefícios para hipertensos. Objetivo: Verificar os efeitos do treinamento físico aeróbico sobre a contratilidade e a concentração intracelular de Ca2+ transitória em miócitos e a expressão do microRNA 214 no ventrículo esquerdo (VE) de ratos espontaneamente hipertensos (SHR). Métodos: SHR e ratos Wistar normotensos com 16 semanas de idade foram divididos em 4 grupos de 13 animais cada: hipertenso sedentário (HS); hipertenso treinado (HT); normotenso sedentário (NS); normotenso treinado (NT). Os animais dos grupos HT e NT foram submetidos a um programa de treinamento progressivo de corrida em esteira, 5 dias/semana, 1 hora/dia, em intensidade de 60-70% da velocidade máxima de corrida, durante 8 semanas. Adotou-se p ≤ 0,05 como nível de significância em todas as comparações. Resultados: O treinamento físico reduziu a pressão arterial sistólica nos animais hipertensos. Nos animais normotensos, o treinamento físico reduziu o tempo para 50% de relaxamento celular e o tempo para o pico de contração celular, mas aumentou o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória. Nos animais SHR, o treinamento físico aumentou a amplitude e reduziu o tempo para 50% de decaimento da concentração intracelular de Ca2+ transitória, sem alterar a contratilidade celular. O treinamento físico aumentou a expressão do miR-214 apenas nos animais hipertensos. Conclusão: O treinamento aeróbico utilizado aumenta a disponibilidade e acelera o sequestro de Ca2+ intracelular em miócitos do VE de ratos hipertensos, apesar do aumento da expressão de miR-214 e da manutenção da contratilidade celular.

Control of Energy Expenditure by AgRP Neurons of the Arcuate Nucleus: Neurocircuitry, Signaling Pathways, and Angiotensin.

PURPOSE OF REVIEW: Here, we review the current understanding of the functional neuroanatomy of neurons expressing Agouti-related peptide (AgRP) and the angiotensin 1A receptor (AT1A) within the arcuate nucleus (ARC) in the control of energy balance. RECENT FINDINGS: The development and maintenance of obesity involves suppression of resting metabolic rate (RMR). RMR control is integrated via AgRP and proopiomelanocortin neurons within the ARC. Their projections to other hypothalamic and extrahypothalamic nuclei contribute to RMR control, though relatively little is known about the contributions of individual projections and the neurotransmitters involved. Recent studies highlight a role for AT1A, localized to AgRP neurons, but the specific function of AT1A within these cells remains unclear. AT1A functions within AgRP neurons to control RMR, but additional work is required to clarify its role within subpopulations of AgRP neurons projecting to distinct second-order nuclei, and the molecular mediators of its signaling within these cells.

Independent association of resting energy expenditure with blood pressure: confirmation in populations of the African diaspora.

BACKGROUND: Obesity is a major risk factor for hypertension, however, the physiologic mechanisms linking increased adiposity to elevations in blood pressure are not well described. An increase in resting energy expenditure (REE) is an obligatory consequence of obesity. Previous survey research has demonstrated that REE is an independent predictor of blood pressure, and eliminates the co-linear association of body mass index. This observation has received little attention and there have been no attempts to provide a causal explanation. METHODS: At baseline in an international comparative study on obesity, 289 participants aged 25-44 were recruited from communities in the US, the Seychelles, Ghana and South Africa and had REE measured with indirect calorimetry. All participants were thought to be free of major illness. RESULTS: In multivariate regression models, both systolic and diastolic blood pressure were positively associated with REE (p < 0.01), while body mass index and fat mass were negatively correlated with systolic blood pressure (p < 0.01, and p < 0.05 respectively), but not diastolic blood pressure. CONCLUSIONS: These data confirm previous reports and suggest that a common physiologic abnormality links REE and blood pressure. Elevated catecholamines, a putative metabolic characteristic of obesity, is a possible candidate to explain this association. The direct role of excess adipose tissue is open to question.

Prevalencia del Síndrome Metabólico en pacientes internadas en el Servicio de Ginecología del Hospital Central. Instituto de Previsión Social, Enero-Junio 2017 / Prevalence of the Metabolic Syndrome in patients admitted to the Gynecology Service of the Central Hospital. Institute of Social Security, January-June 2017

Introducción: El Síndrome Metabólico (SM) es una epidemia y un problema de salud pública, debido a la creciente prevalencia de obesidad y estilos de vida poco saludables. Está asociado a un incremento de 5 veces de riesgo de Diabetes Mellitus tipo 2, y de 2 a 3 veces de aumento en el riesgo de enfermedad cardiovascular, con disminución en la supervivencia. Después de la menopausia, la prevalencia de SM aumenta todavía más, generando un aumento muy significativo del riesgo cardiovascular. Objetivos: Conocer la prevalencia de SM en pacientes internadas de enero a junio del 2017 en el Servicio de Ginecología HC-IPS y comparar la prevalencia de SM obtenida según criterios de la NCEP ATPIII y la IDF en mujeres pre menopáusicas y post menopáusicas. Metodología: Estudio retrospectivo, descriptivo de corte transversal. Resultados: De 380 pacientes observadas, el promedio de edades fue de 43 años.77 % tenían un IMC mayor a 25. 56,8 % eran pre menopáusicas y 43,1 % post menopáusicas. La prevalencia de SM fue diferente según criterios de NCEP ATPIII y la IDF, siendo 23,1 % con el primero y 63 % con el segundo. Se encontró que 80% de las pre menopáusicas y 90 % de las post menopáusicas presentaban IMC mayor a 25. La patología ginecológica mayormente asociada fue el engrosamiento endometrial, observado en un 18% de los casos de SM en las post menopáusicas. En las pre menopáusicas se observó que en el 40% el SM estaba relacionado a HUA y miomatosis uterina. El porcentaje de cáncer endometrial fue bastante importante siendo del 11%. Palabras claves: menopausia, hipertensión, diabetes.

Introduction: The Metabolic Syndrome (MS) is an epidemic and a public health problem, due to the growing prevalence of obesity and unhealthy lifestyles. It is associated with a 5-fold increase in the risk of Diabetes Mellitus type 2, and a 2 to 3-fold increase in the risk of cardiovascular disease, with a decrease in survival. After menopause, the prevalence of MS increases even more, generating a very significant increase in cardiovascular risk. Objectives: To know the prevalence of MS in patients hospitalized from January to June 2017 in the HC-IPS Gynecology Service and to compare the prevalence of MS obtained according to NCEP ATPIII and IDF criteria in premenopausal and postmenopausal women. Methodology: Retrospective, descriptive crosssectional study. Results: Of 380 patients observed, the average age was 43.77% had a BMI greater than 25. 56.8% were premenopausal and 43.1% postmenopausal. The prevalence of MS was different according to the criteria of NCEP ATPIII and the IDF, being 23.1% with the first and 63% with the second. It was found that 80% of premenopausal and 90% of postmenopausal women had a BMI greater than 25. The gynecological pathology most associated was endometrial thickening, observed in 18% of cases of MS in postmenopausal women. In premenopausal women it was observed that in 40% the MS was related to HUA and uterine myomatosis. The percentage of endometrial cancer was quite important being 11%. Keywords: menopause, hypertension, diabetes

Assessment of preclinical pharmacokinetics and acute toxicity of pioglitazone and telmisartan combination.

The prevalence of hypertension is very common amongst the diabetic patients and is reported as the major cause of mortality in diabetes. Pioglitazone reported to have an ability to alter the blood cholesterol level and cardioprotective efficiency along with its antidiabetic activity. Telmisartan, through activation of PPAR-γ receptor exerts insulin sensitizing property in addition to its primary cardioprotective efficiency. Theoretically, a combination of pioglitazone and telmisartan may be beneficial to effectively control the high blood glucose level and management of coexisting cardiovascular complication in diabetes. The aim of this research was to experimentally evaluate the pharmacokinetic interaction of pioglitazone and telmisartan when are coadministered in rat. Pioglitazone and telmisartan were administered orally as a single dose individually and in combination to the rats. The plasma samples of the pharmacokinetic study were analyzed using a validated LCMS method. The acute toxicity of the combination with a high dose in rats was also evaluated as a part of the determination of its safety profile. There was no significant change in pharmacokinetic parameters were resulted due to the coadministration of pioglitazone and telmisartan in rat. Absence of major toxicological effect supports the in vivosafety of the combination.

Characterization of Metabolically Healthy Obese People and Metabolically Unhealthy Normal-Weight People in a General Population Cohort of the ABCD Study.

There is actually no consensus about the possibility that in some instances, obesity may be a benign metabolically healthy (MH) condition as opposed to a normal-weight but metabolically unhealthy (MUH) state. The aim of this study was to characterize MH condition and to investigate possible associations with metabolic and cardiovascular complications. One thousand nineteen people (range of age 18-90 years) of the cohort of the ABCD_2 study were investigated. Participants were classified as normal weight (BMI < 24.9 kg/m2) or overweight-obese (BMI ≥25 kg/m2); they were also classified as MH in the presence of 0-1 among the following conditions: (a) prediabetes/type 2 diabetes, (b) hypertension, (c) hypertriglyceridemia or low HDL cholesterolemia, and (d) hypercholesterolemia. MUH condition was diagnosed if ≥2 of the conditions listed were found. The prevalence of overweight/obese people was 71.1%, of whom 27.4% were found to be MH. In addition, 36.7% of the normal-weight participants were MUH. HOMA-IR, high sensitivity C-reactive protein, and the carotid intima-media thickness were significantly different in the 4 subgroups (P < 0.001), with higher values observed in the MUH normal-weight and obese groups. In conclusion, this study highlights the importance of identifying a MH condition in normal-weight and in obese people in order to offer better treatment.

Hypertension is associated with worse cognitive function and hippocampal hypometabolism in Alzheimer's disease.

BACKGROUND AND PURPOSE: A growing body of evidence suggests that cardiovascular disease risk factors including hypertension may be linked to sporadic Alzheimer's disease (AD). It is well known that hypertension is associated with cerebrovascular disease and vascular dementia on the basis of vascular remodeling. However, the mechanisms linking hypertension and AD remain unclear. METHODS: We studied 197 patients with AD (86 male; mean age ± SD: 75.8 ± 7.4 years) from the Alzheimer's Disease Neuroimaging Initiative database with (n = 97) and without (n = 100) hypertension. We explored associations between hypertension and clinical, plasma, cerebrospinal fluid and imaging markers of AD pathology in order to elucidate the underlying mechanisms that may link AD and hypertension. RESULTS: We found that patients with AD with hypertension had worse cognitive function (Alzheimer's disease Assessment Scale-cognitive subscale, P = 0.038) and higher neuropsychiatric symptom burden (Neuropsychiatric Inventory Questionnaire, P = 0.016) compared with those without hypertension. Patients with AD with hypertension showed reduced glucose hypometabolism in the right (P < 0.001) and left (P = 0.007) hippocampus. No differences were found in magnetic resonance imaging volumetric measurements, [18 F]florbetapir uptakes, plasma and cerebrospinal fluid between patients with AD with and without hypertension. CONCLUSIONS: Although hypertension is associated with worse cognitive function, behavioural symptoms and hippocampal glucose hypometabolism, it is not associated with evidence of increased amyloid or tau pathology. Effective management of hypertension may potentially have a therapeutic role in the alleviation of symptoms in AD.