Pro-inflammatory Cytokines and Resistant Hypertension: Potential for Novel Treatments?

PURPOSE OF REVIEW: To gather data from studies evaluating the pro-inflammatory profile of individuals with resistant hypertension (RH), and bring a clinical update of new and potential complementary therapies to treat inflammation in RH. RECENT FINDINGS: Increases in pro-inflammatory cytokines are related to elevated blood pressure and target organ damage in RH patients. Clinical and experimental studies have shown that some biological therapies, especially TNF-α inhibitors, regulated pro- and anti-inflammatory cytokines associated with improvements in clinical outcomes, although they are not yet reported in RH. New emerging therapies to treat inflammation in RH, although promising, are still hypotheses that have not been scientifically confirmed in clinical trials. For this reason, inflammation-target treatments, such as the TNF-α and IL-6 inhibitors, should be encouraged for testing as complementary therapies in RH in order to elucidate their potential benefits.

Effects of leptin and leptin receptor SNPs on clinical- and metabolic-related traits in apparent treatment-resistant hypertension.

Leptin is associated to the lack of blood pressure control as well as target organ damage in resistant hypertensive (RH) subjects. Single-nucleotide polymorphisms (SNPs) rs7799039 and rs1137101 in leptin (LEP) and leptin receptor (LEPR) genes, respectively, are associated with cardiovascular disease and metabolic syndrome. We evaluated the association of these two SNPs with clinical and biochemical features in 109 apparent treatment-RH subjects (aTRH) and 125 controlled hypertensives. Homozygous genotypes GG (n = 43) vs. AA (n = 14) for rs7799039 and AA (n = 34) vs. GG (n = 26) genotypes for rs1137101 were compared in aTRH subjects. There was no difference in leptin levels among both SNPs. On the other hand, LEP SNP (GG vs. AA) associated with the levels of glycated haemoglobin (6.4 ± 1.4 vs. 7.8 ± 2.3%, p = 0.03), insulin (8.6 ± 4.6 vs. 30.6 ± 27.7 uUI/mL, p = 0.01), HDL-cholesterol (51 ± 16 vs. 39 ± 11 mg/dL, p = 0.001) and PWV (9.5 ± 2.1 vs. 11.2 ± 2.8 m/s, p = 0.03). LEPR SNP (AA vs. GG), associated with heart rate (69 ± 12 vs. 67 ± 12 bpm, p = 0.03), fat mass (31 ± 11 vs. 24 ± 8 kg, p = 0.03) and triglycerides levels (175 ± 69 vs. 135 ± 75 mg/dL, p = 0.03). These findings may be clinically useful for identifying a group of aTRH who may have a LEP and/or LEPR gene variants, which may predispose this specific group to worse or better outcomes.

Crosstalk between obesity and MMP-9 in cardiac remodelling -a cross-sectional study in apparent treatment-resistant hypertension.

The balance between matrix metalloproteinases (MMP) and their tissue inhibitors (TIMP) plays a key role in the development of hypertension and obesity. We aimed to evaluate the levels of MMP-2 and 9 and TIMP-2 and -1 in obese and non-obese apparent treatment-resistant hypertensive subjects (aTRH) and its association with cardiac hypertrophy. This cross-sectional study enrolled 122 subjects and divided into obese aTRH (n = 67) and non-obese (n = 55) group. Clinical and biochemical data were compared between both groups, including office BP, ambulatory BP, plasma MMP-2 and 9, TIMP-2 and 1 and left ventricular mass index (LVMI). We found higher MMP-9 levels and MMP-9/TIMP-1 ratio in obese aTRH subjects but no difference in MMP-2 and TIMP-1 levels. Obesity influenced MMP-9 levels [ß = 20.8 SE =8.6, p = 0.02) independently of potential confounders. In addition, we found a positive correlation between MMP-9 and anthropomorphic parameters. Finally, obese aTRH subjects with left ventricular hypertrophy (LVH) had greater MMP-9 levels compared with non-obese with LVH. Our study suggests that MMP-9 levels are influenced by obesity and may directly participate in the progressive LV remodelling process, suggesting a possible role for a higher cardiovascular risk in apparent resistant hypertensive subjects.

Effect of oil palm on the Plecoptera and Trichoptera (Insecta) assemblages in streams of eastern Amazon.

The production of oil palm is expected to increase in the Amazon region. However, expansion of oil palm plantation leads to significant changes in the physical structure of aquatic ecosystems, mainly through the reduction of riparian vegetation that is essential for aquatic biodiversity. Here, we evaluated the effects of oil palm on the physical habitat structure of Amazonian stream environments and assemblages of Plecoptera and Trichoptera (PT), ​both found in these streams. We compared streams sampled in oil palm plantations (n = 13) with natural forest areas ("reference" streams, n = 8), located in the eastern Amazon, Brazil. Our results showed that oil palm streams were more likely to be in close proximity to roads, had higher pH values, and higher amounts of fine substrate deposited in the channel than reference streams. Further, these environmental changes had important effects on the aquatic invertebrate assemblages, reducing the abundance and richness of PT. Nevertheless, the genera composition of the assemblages did not differ between reference and oil palm (PERMANOVA, pseudo-F (1,19) = 1.891; p = 0.111). We conclude that oil palm production has clear negative impacts on aquatic environments and PT assemblages in Amazonian streams. We recommend that oil palm producers invest more in planning of road networks to avoid the construction of roads near to the riparian vegetation. This planning can minimize impacts of oil palm production on aquatic systems in the Amazon.

Deregulation of Soluble Adhesion Molecules in Resistant Hypertension and Its Role in Cardiovascular Remodeling.

BACKGROUND: Resistant hypertension (RHTN) and target organ damage are linked to increased inflammatory biomarkers, which may regulate adhesion molecules, such as intracellular adhesion molecule-1 (ICAM-1); vascular cell adhesion molecule-1 (VCAM-1); and the platelet (P-selectin) and endothelial (E-selectin) selectins. We investigated a previously unknown relationship between soluble P-selectin (sP-selectin), E-selectin (sE-selectin), ICAM-1 (sICAM-1) and VCAM-1 (sVCAM-1) with RHTN and target organ damage. METHODS AND RESULTS: We included 110 subjects diagnosed for true RHTN and 112 mild-moderate hypertensive (HTN) patients. Blood pressure parameters, pulse wave velocity and left ventricular mass index (LVMI) were measured. Adhesion molecules were measured on ELISA. Both sP-selectin and sE-selectin were increased; in contrast, sICAM-1 was reduced in RHTN compared with HTN patients, while similar sVCAM-1 was noted in the groups. sP-selectin and sVCAM-1 were elevated in the presence of arterial stiffness (sP-selectin: 104±47 vs. 89±45 ng/ml, P<0.05; sVCAM-1: 1,189±411 vs. 1,060±412 ng/ml, P<0.05) and cardiac hypertrophy (sP-selectin: 105±51 vs. 88±43 ng/ml, P<0.05; sVCAM-1: 1,170±433 vs. 1,040±383 ng/ml, P<0.05) in all HTN patients. sP-selectin was associated with target organ damage after adjustment for age and BP. Apart from potential confounders, sE-selectin was a significant indicator of RHTN. CONCLUSIONS: The adhesion molecule sP-selectin plays a role in cardiovascular damage, and sE-selectin in resistance to antihypertensive therapy. (Circ J 2016; 80: 1196-1201).

Increased arterial stiffness in resistant hypertension is associated with inflammatory biomarkers.

BACKGROUND: Increased levels of inflammatory biomarkers such as interleukin-6 (IL-6), 10 (IL-10), 1ß (IL-1ß), tumor necrosis factor-α (TNF-α) high-sensitivity C-reactive protein (hs-CRP) are associated with arterial stiffness in hypertension. Indeed, resistant hypertension (RHTN) leads to unfavorable prognosis attributed to poor blood pressure (BP) control and target organ damage. This study evaluated the potential impact of inflammatory biomarkers on arterial stiffness in RHTN. METHODS: In this cross-sectional study, 32 RHTN, 20 mild hypertensive (HTN) and 20 normotensive (NT) patients were subjected to office BP and arterial stiffness measurements assessed by pulse wave velocity (PWV). Inflammatory biomarkers were measured in plasma samples. RESULTS: PWV was increased in RHTN compared with HTN and NT (p < 0.05). TNF-α levels were significantly higher in RHTN and HTN than NT patients. No differences in IL-6 levels were observed. RHTN patients had a higher frequency of subjects with increased levels of IL-10 and IL-1ß compared with HTN and NT patients. Finally, IL-1ß was independently associated with PWV (p < 0.001; R(2) = 0.5; ß = 0.077). CONCLUSION: RHTN subjects have higher levels of inflammatory cytokines (TNF-α, IL-1ß and IL-10) as well as increased arterial stiffness, and detectable IL-1ß levels are associated arterial stiffness. These findings suggest that inflammation plays a possible role in the pathophysiology of RHTN.

Resistant or refractory hypertension: are they different?

Resistant hypertension (RHTN) consists in a condition where blood pressure (BP) levels remain uncontrolled despite the use of at least three drugs or if the control happens with four or more drugs. Throughout the last 50 years, it has been increasingly studied, and its phenotypes have been identified. The term refractory hypertension has been used concurrently with RHTN all those years, but in the last decade, it has been applied to the most afflicted part of RHTN--defined as the uncontrolled RHTN or as the uncontrolled RHTN who needs five or more drugs. Differences between those two phenotypes are being recently identified, especially classifying refractory subjects as having more: (1) cardiovascular risk, (2) target organ damage, (3) African-descending race, (4) coronary heart disease and myocardial ischemia, (5) aldosterone excess, (6) deregulation of adipokines, and (7) possible sympathetic hyperactivation. We review the most important studies in both resistant and refractory hypertension to gather the up-to-date data regarding the characteristics of these two high-risk groups of patients.

Tadalafil-induced improvement in left ventricular diastolic function in resistant hypertension.

PURPOSE: Left ventricular hypertrophy and diastolic dysfunction (LVDD) remain highly frequent markers of cardiac damage and risk of progression to symptomatic heart failure, especially in resistant hypertension (RHTN). We have previously demonstrated that administration of sildenafil in hypertensive rats improves LVDD, restoring phosphodiesterase type 5 (PDE-5) inhibition in cardiac myocytes. METHODS: We hypothesized that the long-acting PDE-5 inhibitor tadalafil may be clinically useful in improving LVDD in RHTN independently of blood pressure (BP) reduction. A single blinded, placebo-controlled, crossover study enrolled 19 patients with both RHTN and LVDD. Firstly, subjects received tadalafil (20 mg) for 14 days and after a 2-week washout period, they received placebo orally for 14 days. Patients were evaluated by office BP and ambulatory BP monitoring (ABPM), endothelial function (FMD), echocardiography, plasma brain natriuretic peptide (BNP-32), cyclic guanosine monophosphate (cGMP) and nitrite levels. RESULTS: No significant differences were detected in BP measurements. Remarkably, at least four echocardiographic parameters related with diastolic function improved accompanied by decrease in BNP-32 in tadalafil use. Although increasing cGMP, tadalafil did not change endothelial function or nitrites. There were no changes in those parameters after placebo. CONCLUSION: The current findings suggest that tadalafil improves LV relaxation through direct effects PDE-5-mediated in the cardiomyocytes with potential benefit as an adjunct to treat symptomatic subjects with LVDD such as RHTN patients.

The white-coat effect is an independent predictor of myocardial ischemia in resistant hypertension.

White-coat hypertension (WCH), commonly found in pseudoresistant hypertension, does not pose higher cardiovascular risk than hypertensive status. However, when the decrease of the out-of-office blood pressure does not reach normal levels - the white-coat effect (WCE) - the repercussions are still obscure. We investigated the repercussions of the WCE in myocardial perfusion in resistant hypertension (RHTN). We enrolled 129 asymptomatic RHTN subjects - divided into WCE (n = 63) and non-WCE (n = 66) - to perform rest and stress myocardial perfusion scintigraphy and biochemical tests. Groups were equal regarding age, gender and body mass index. There was a high prevalence of WCE (49%). WCE was associated with higher prevalence of myocardial ischemia (49.2% vs 7.6%, p < 0.001), microalbuminuria (60.3% vs 36.4%, p = 0.01) and higher heart rate (72 [64-80] vs 64 [60-69], p < 0.001), compared with non-WCE patients. On an adjusted logistic regression, heart rate was considered a predictor of WCE (OR = 1.10, 95% CI 1.04-1.15; p < 0.001), but not MA (OR = 1.8, 95% CI 0.8-3.9; p = 0.15). On a second model of adjusted logistic regression, WCE was an independent predictor of myocardial ischemia (OR = 14.7, 95% CI 4.8-44.8; p < 0.001). We found a high prevalence of WCE in RHTN, and this effect may predict silent myocardial ischemia in this subset of hypertensive patients. In this group of hypertensives special attention should be given to the WCE.

Systematic challenges and opportunities in insect monitoring: a Global South perspective.

Insect monitoring is pivotal for assessing biodiversity and informing conservation strategies. This study delves into the complex realm of insect monitoring in the Global South-world developing and least-developed countries as identified by the United Nations Conference on Trade and Development-highlighting challenges and proposing strategic solutions. An analysis of publications from 1990 to 2024 reveals an imbalance in research contributions between the Global North and South, highlighting disparities in entomological research and the scarcity of taxonomic expertise in the Global South. We discuss the socio-economic factors that exacerbate the issues, including funding disparities, challenges in collaboration, infrastructure deficits, information technology obstacles and the impact of local currency devaluation. In addition, we emphasize the crucial role of environmental factors in shaping insect diversity, particularly in tropical regions facing multiple challenges including climate change, urbanization, pollution and various anthropogenic activities. We also stress the need for entomologists to advocate for ecosystem services provided by insects in addressing environmental issues. To enhance monitoring capacity, we propose strategies such as community engagement, outreach programmes and cultural activities to instill biodiversity appreciation. Further, language inclusivity and social media use are emphasized for effective communication. More collaborations with Global North counterparts, particularly in areas of molecular biology and remote sensing, are suggested for technological advancements. In conclusion, advocating for these strategies-global collaborations, a diverse entomological community and the integration of transverse disciplines-aims to address challenges and foster inclusive, sustainable insect monitoring in the Global South, contributing significantly to biodiversity conservation and overall ecosystem health. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Acute cardiac and hemodynamic effects of sildenafil on resistant hypertension.

PURPOSE: Failure to control blood pressure (BP) despite the use of three or more drugs characterizes resistant hypertension (RHTN). Impaired endothelial function is associated with this condition and phosphodiesterase-5 inhibitors (PDE5i)-inhibiting cGMP breakdown-reduce BP in RHTN patients. We hypothesized that acute administration of PDE5i could ameliorate hemodynamic, endothelial parameters and left ventricular diastolic function (LVDF) in RHTN patients. Also, an exploratory analysis was performed to assess the influence of the T-786C endothelial NO synthase polymorphism on those responses. METHODS: Subjects (n = 26) underwent a 6-month clinical screening for RHTN diagnosis. Increasing doses of oral sildenafil were given at 30 min intervals (37.5, 50 and 100 mg) while continuous non-invasive hemodynamic measures were assessed. LVDF, flow mediated dilation (FMD), nitrite and cGMP levels were also determined. RESULTS: Mean arterial pressure and total peripheral resistance decreased in all patients (84.17 ± 21.04 to 75 ± 17.21 mmHg; 1149 ± 459.7 to 1037 ± 340 dyn.s/cm(-5), respectively). Likewise, sildenafil improved diastolic dysfunction parameters (Left atrial volume: 25 ± 5.8 to 20 ± 4.4; IVRT: 104 ± 19.33 to 88 ± 15.22; E/e' septal: 9.7 ± 3.8 to 7.9 ± 2.9; E/e' lateral: 7.7 ± 3.4 to 6.4 ± 3.2). No statistical changes were found in FMD, nitrite and cGMP with PDE5i. CONCLUSION: Our data suggest PDE5i acutely improves diastolic function and hemodynamic profile in RHTN subjects, despite unchanging endothelial dysfunction.

Vascular stiffness and endothelial dysfunction: Correlations at different levels of blood pressure.

UNLABELLED: Resistant hypertensive (RHTN) patients have endothelial dysfunction and aldosterone excess, which contribute to the development of resistance to antihypertensive treatment and cardiovascular complications. Biophysical forces within the arterial wall provide functional regulation of arterial stiffness. Carotid-femoral pulse wave velocity (PWV) and flow-mediated brachial artery dilation (FMD) can be used to evaluate vascular stiffness and endothelial function. Although both techniques have been used in several studies in hypertensive patients, it is unknown whether endothelial dysfunction is also associated with vascular stiffness in RHTN patients. METHODS: One hundred and ninety-three consecutive subjects were divided in three groups: 44 RHTN, 35 well-controlled hypertensive patients (HTN) and 25 normal healthy volunteers (NT). FMD was measured by high-resolution ultrasound and PWV was calculated from measurements of the pulse transit time and the distance traveled by the pulse between carotid and femoral arteries. RESULTS: No significant differences were observed in respect to body mass index, age or other biochemical variables among the three groups. FMD (NO-dependent) values were statistically different when comparing RHTN and well controlled HTN patients (respectively, 8.3 ± 4.7% and 10.1 ± 5.9%) and 12.3 ± 6.3% in normal subjects (p < 0.05). One-way analysis of variance (ANOVA) showed a significant difference in BP-adjusted PWV between RHTN and HTN (13.9 ± 1.0 and 11.5 ± 1.1 m/s, respectively; p < 0.05). FMD (NO-dependent) and PWV-adjusted values were strongly correlated in well-controlled HTN and NT subjects (r = - 0.74 and - 0.83, respectively). Although statistically significant, this correlation was lower in RHTN patients (r = - 0.43). CONCLUSION: We found a close relationship among high BP levels, endothelial dysfunction and vascular rigidity in hypertensive patients, demonstrated by a significantly higher increase in carotid-femoral PWV and a decrease in brachial artery FMD in RHTN when compared with well-controlled hypertensive patients. Although this study was not designed to test the prognostic, the vascular damage differences observed between patients with controlled vs uncontrolled hypertension suggest that the latter group may have a worse cardiovascular prognosis, requiring prospective assessment tests.

Cardiovascular Autonomic Responses to Aerobic, Resistance and Combined Exercises in Resistance Hypertensive Patients.

Here, we report the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure, central blood pressure and augmentation index, hemodynamic parameters, and autonomic modulation of resistant (RH) and nonresistant hypertensive (NON-RH) subjects. Twenty participants (10 RH and 10 NON-RH) performed three exercise sessions (i.e., AER, RES, and COM) and a control session. Hemodynamic (Finometer®, Beatscope), office blood pressure (BP), and autonomic variables (accessed through spectral analysis of the pulse-to-pulse BP signal, in the time and frequency domain-Fast Fourrier Transform) were assessed before (T0), one-hour (T1), and twenty-four (T2) hours after each experimental session. There were no changes in office BP, pulse wave behavior, and hemodynamic parameters after (T0 and T1) exercise sessions. However, AER and COM exercises significantly reduced sympathetic modulation in RH patients. It is worth mentioning that more significant changes in sympathetic modulation were observed after AER as compared to COM exercise. These findings suggest that office blood pressure, arterial stiffness, and hemodynamic parameters returned to baseline levels in the first hour and remained stable in the 24 hours after the all-exercise sessions. Notably, our findings bring new light to the effects of exercise on RH, indicating that RH patients show different autonomic responses to exercise compared to NON-RH patients. This trial is registered with trial registration number NCT02987452.

Combined Aerobic and Resistance Exercises Evokes Longer Reductions on Ambulatory Blood Pressure in Resistant Hypertension: A Randomized Crossover Trial.

AIM: The present study compared the acute effects of aerobic (AER), resistance (RES), and combined (COM) exercises on blood pressure (BP) levels in people with resistant hypertension (RH) and nonresistant hypertension (NON-RH). METHODS: Twenty patients (10 RH and 10 NON-RH) were recruited and randomly performed three exercise sessions and a control session. Ambulatory BP was monitored over 24 hours after each experimental session. RESULTS: Significant reductions on ambulatory BP were found in people with RH after AER, RES, and COM sessions. Notably, ambulatory BP was reduced during awake-time and night-time periods after COM. On the other hand, the effects of AER were more prominent during awake periods, while RES caused greater reductions during the night-time period. In NON-RH, only RES acutely reduced systolic BP, while diastolic BP was reduced after all exercise sessions. However, the longest postexercise ambulatory hypotension was observed after AER (~11 h) in comparison to RES (~8 h) and COM (~4 h) exercises. CONCLUSION: Findings of the present study indicate that AER, RES, and COM exercises elicit systolic and diastolic postexercise ambulatory hypotension in RH patients. Notably, longer hypotension periods were observed after COM exercise. In addition, NON-RH and RH people showed different changes on BP after exercise sessions, suggesting that postexercise hypotension is influenced by the pathophysiological bases of hypertension.

Association of Pulse Pressure With Clinical Outcomes in Patients Under Different Antiplatelet Strategies After Percutaneous Coronary Intervention: Analysis of GLOBAL LEADERS.

BACKGROUND: We evaluated the association of pulse pressure (PP) and different antiplatelet regimes with clinical and safety outcomes in an all-comers percutaneous coronary intervention (PCI) population. METHODS: In this analysis of GLOBAL LEADERS (n = 15,936) we compared the experimental therapy of 23 months of ticagrelor after 1 month of dual-antiplatelet therapy (DAPT) vs standard DAPT for 12 months followed by aspirin monotherapy in subjects who underwent PCI and were divided into 2 groups according to the median PP (60 mm Hg). The primary end point (all-cause death or new Q-wave myocardial infarction) and the composite end points: patient-oriented composite end points (POCE), Bleeding Academic Research Consortium (BARC) 3 or 5, and net adverse clinical events (NACE) were evaluated. RESULTS: At 2 years, subjects in the high-PP group (n = 7971) had similar rates of the primary end point (4.3% vs 3.9%; P = 0.058), POCE (14.9% vs 12.7%; P = 0.051), and BARC 3 or 5 (2.5% vs 1.7%; P = 0.355) and higher rates of NACE (16.4% vs 13.7%; P = 0.037) compared with the low-PP group (n = 7965). Among patients with PP < 60 mm Hg, the primary end point (3.4% vs 4.4%, adjusted hazard ratio [aHR] 0.77, 95% confidence interval [CI] 0.61-0.96), POCE (11.8% vs 13.5%, aHR 0.86, 95% CI 0.76-0.98), NACE (12.8% vs 14.7%, aHR 0.85, 95% CI 0.76-0.96), and BARC 3 or 5 (1.4% vs 2.1%, aHR 0.69, 95% CI 0.49-0.97) were lower with ticagrelor monotherapy compared with DAPT. The only significant interaction was for BARC 3 or 5 (P = 0.008). CONCLUSIONS: After contemporary PCI, subjects with high PP levels experienced high rates of NACE at 2 years. In those with low PP, ticagrelor monotherapy led to a lower risk of bleeding events compared with standard DAPT.

[The everyday life of people living with the chronic condition of diabetes mellitus]. / A vida cotidiana de quem vivencia a condição crônica do diabetes mellitus.

The objective of this study was to understand the experience of a person with diabetes mellitus and how that person deals with adversity in everyday life. Data collection was performed by means of a Focal Life History questionnaire and by observing health care professionals. Data analysis was based on the comprehensive approach, which permitted understanding the everyday life as a scenario for those living with the experience of falling ill and searching for care, considering that this experience is unique and personal. It is impossible to create health care practices that disregard the everyday life and health situation of the person. Furthermore, it is impossible to propose such practice without the active participation of the person affected by those decisions and conducts.

White coat syndrome and its variations: differences and clinical impact.

Hypertension is closely linked to increased cardiovascular risk and development of target organ damage (TOD). Therefore, proper clinical follow-up and treatment of hypertensive subjects are mandatory. A great number of individuals present a variation on blood pressure (BP) levels when they are assessed either in the office or in the out-of-office settings. This phenomenon is defined as white coat syndrome - a change in BP levels due to the presence of a physician or other health professional. In this context, the term "white coat syndrome" may refer to three important and different clinical conditions: 1) white coat hypertension, 2) white coat effect, and 3) masked hypertension. The development of TOD and the increased cardiovascular risk play different roles in these specific subgroups of white coat syndrome. Correct diagnose and clinical guidance are essential to improve the prognosis of these patients. The aim of this review was to elucidate contemporary aspects of these types of white coat syndrome on general and hypertensive population.

Effect of seasonality on the leaf phenology and physiology of Byrsonima species (Malpighiaceae)

Introduction: Defined seasonality in savanna species can stimulate physiological responses that maximize photosynthetic metabolism and productivity. However, those physiological responses are also linked to the phenological status of the whole plant, including leaf phenophases. Objective: To study how physiological traits influence phenophase timing among congeneric and co-occurring savanna species. Methods: We evaluated the leaf phenology and physiological traits of populations of Byrsonima intermedia, B. coccolobifolia, and B. verbascifolia. Physiological measurements were performed at the onset of the dry and rainy seasons and again late in the season. Results: B. intermedia and B. coccolobifolia were classified as brevideciduous and B. verbascifolia as evergreen. The maximum quantum yield for B. intermedia and B. coccolobifolia were lowest during the dry season. At the onset of the dry period, the highest chloroplastidic pigment levels were observed, which decreased as the season advanced, total chlorophyll/carotenoid ratios were lowest, and carotenoid contents were highest. We detected low starch content values at the start of the rainy season, coinciding with the resumption of plant growth. Two months into this season, the leaves were at their peak structural and functional maturity, with high water-soluble polysaccharide values and photosynthetic rates, and were storing large amounts of starch. Conclusions: Physiological and leaf phenological strategies of the Byrsonima species were related to drought resistance and acclimatization to the seasonality of savanna water resources. The oscillations of the parameters quantified during the year indicated a strong relationship with water seasonality and with the phenological status of the leaves.

Introducción: La marcada estacionalidad en las especies de sabana puede estimular respuestas fisiológicas que maximicen el metabolismo fotosintético y la productividad. Sin embargo, esas respuestas fisiológicas están vinculadas al estado fenológico de toda la planta, incluidas las fenofases de las hojas. Objetivo: Estudiar cómo los rasgos fisiológicos influyen en el tiempo de la fenofase entre especies de sabana congenéricas y concurrentes. Métodos: Evaluamos la fenología y características fisiológicas de poblaciones de Byrsonima intermedia, B. coccolobifolia y B. verbascifolia. Las mediciones fisiológicas se realizaron al inicio de la estación seca y lluviosa, y de nuevo al final de la estación. Resultados: B. intermedia y B. coccolobifolia se clasificaron como brevicaducifolias y B. verbascifolia como perennifolias. El rendimiento cuántico máximo para B. intermedia y B. coccolobifolia fueron más bajos durante la época seca. Al inicio del período seco, se observaron niveles de pigmentos cloroplastídicos más altos, aunque los niveles de clorofila disminuyeron a medida que avanzaba la estación seca, las proporciones clorofila/carotenoides totales fueron más bajas y los contenidos de carotenoides más altos. Detectamos valores bajos de contenido de almidón al inicio de la época lluviosa, que coincide con la reanudación del crecimiento de la planta. A dos meses de esta época, las hojas estaban en su máxima madurez estructural y funcional, con altos valores de polisacáridos solubles en agua y tasas fotosintéticas, y almacenaban grandes cantidades de almidón. Conclusiones: Las estrategias fisiológicas y fenológicas de las hojas de las especies de Byrsonima estaban relacionadas con la resistencia a la sequía y la aclimatación a la estacionalidad de los recursos hídricos de la sabana. Las oscilaciones de los parámetros cuantificados durante el año indicaron una fuerte relación con la estacionalidad hídrica y con los estados fenológicos de las hojas.

The rs243866/243865 polymorphisms in MMP-2 gene and the relationship with BP control in obese resistant hypertensive subjects.

We sought to investigate whether the polymorphisms rs243865 (-1306C>T); rs243866 (-1575G>A) and rs2285053 (-735C>T) in metalloproteinases 2 - MMP-2 gene and rs17576 (Q279R), rs17577 (Q668R) and rs3918242 (-1562C>T) in MMP-9 gene are associated with clinical outcomes in obese resistant hypertensive (RH) subjects. One hundred and twenty RH were enrolled in this cross-sectional study and divided into obese (n=63) and non-obese (n=57) according to body mass index. Genotypes were determined by real-time PCR using TaqMan probes. We determined pulse wave velocity (PWV), microalbuminuria and left ventricular mass index (LVMI) to assess TODs. Obese and non-obese RH had similar allele, genotype and haplotype distributions for all polymorphisms assessed but obese RH subjects carrying the low frequency allele for SNPs in MMP-2 gene had higher ambulatory diastolic blood pressure. Also, PWV and LVMI were higher in subjects carrying the low frequency allele for SNPs in MMP-2 gene. Regarding MMP-9 gene, office diastolic BP levels were higher in the AA genotype individuals compared to the G allele group for rs17576 polymorphism, while the opposite was found regarding the microalbuminuria level. Independent multiple linear regression analyses revealed that both A allele for rs243865 and T allele for rs243866 in MMP-2 gene were associated with ambulatory diastolic levels in obese RH subjects, apart from potential confounders. Our study suggests that rs243866/rs243865 in the MMP-2 gene are related to BP levels in obese RH subjects, although TODs present in this population seem to be dependent of a combination of other factors besides the genetic polymorphisms.

Glycated hemoglobin correlates with arterial stiffness and endothelial dysfunction in patients with resistant hypertension and uncontrolled diabetes mellitus.

This study aimed to evaluate the effects of glycated hemoglobin (HbA1c ) on flow-mediated dilation, intima-media thickness, pulse wave velocity, and left ventricular mass index in patients with resistant hypertension (RHTN) comparing RHTN-controlled diabetes mellitus and RHTN-uncontrolled type 2 diabetes mellitus. Two groups were formed: HbA1c <7.0% (RHTN-controlled diabetes mellitus: n = 98) and HbA1c ≥7.0% (RHTN-uncontrolled diabetes mellitus: n = 122). Intima-media thickness and flow-mediated dilation were measured by high-resolution ultrasound, left ventricular mass index by echocardiography, and arterial stiffness by carotid-femoral pulse wave velocity. No differences in blood pressure levels were found between the groups but body mass index was higher in patients with RHTN-uncontrolled diabetes mellitus. Endothelial dysfunction and arterial stiffness were worse in patients with RHTN-uncontrolled diabetes mellitus. Intima-media thickness and left ventricular mass index measurements were similar between the groups. After adjustments, multiple linear regression analyses showed that HbA1c was an independent predictor of flow-mediated dilation and pulse wave velocity in all patients with RHTN. In conclusion, HbA1c may predict the grade of arterial stiffness and endothelial dysfunction in patients with RHTN, and superimposed uncontrolled diabetes mellitus implicates further impairment of vascular function.