Prevalence, management and ethnobotanical investigation of hypertension in two Guinean urban districts.

ETHNOPHARMACOLOGICAL RELEVANCE: Hypertension is an important public health challenge in low- and middle-income countries, and in many African countries including Guinea medicinal plants are still widely used for its treatment. MATERIALS AND METHODS: The objective of this study was to determine the prevalence of hypertension in two Guinean urban districts (Pounthioun and Dowsare), to describe its management and to collect information on traditional herbal remedies. A total of 316 participants entered the study, 28.2% (89/316) men and 71.8% (227/316) women. Of these, 181 were from Dowsare (50 men and 131 women) and 135 from Pounthioun (39 men and 96 women). The mean age of subjects was 40.8 ±â€¯14.0 years (range18 - 88years), while the majority of subjects (63.3% or 200/316) were 45-74 years old. RESULTS: The overall prevalence of hypertension was 44.9% (142/316): 46.4% (84/181) from Dowsare and 43.0% (58/135) from Pounthioun. Ethnobotanical investigations among hypertensive patients led to the collection of 15 plant species, among which Hymenocardia acida leaves and Uapaca togoensis stem bark were the most cited. Phytochemical investigation of these two plant species led to the isolation and identification of isovitexin and isoorientin from H. acida, and betulinic acid and lupeol from U. togoensis. CONCLUSION: The presence of these constituents in Hymenocardia acida leaves and Uapaca togoensis stem bark may at least in part support their traditional use against hypertension in Guinea.

[Input of a laboratory in the management of patients with Ebola virus disease and in the training of health personnel: experience of the Forecariah Ebola treatment centre (Guinea) in 2015]. / Apport d'un laboratoire dans la prise en charge des patients atteints de la maladie à virus Ebola et dans la formation des personnels soignants : expérience du Centre de traitement d'Ebola de Forécariah (Guinée) en 2015.

Ebola virus disease (EVD) is associated with a high lethality rate even when the afflicted are provided with good support in an Ebola treatment center (ETC). Basic laboratory tests can help to better understand the pathophysiology of the disease, to guide treatment and to establish simple protocols and procedures tailored to the practice of medicine in the context of such precarious environment for caregivers. Based on a few clinical cases of patients treated in the ETC of Forecariah, Guinea, run by the French Red Cross, this article describes the difficult conditions associated with the provision of medical practice in this challenging environment, aiming to minimize the casualties in the EVD patient and to train the health staff.

[The register of activity at the Ebola treatment center in Forecariah (Guinea) from april 23 to june 5, 2015: analysis and thoughts]. / Bilan d'activité du centre de traitement Ebola de Forécariah (Guinée) du 23 avril au 5 juin 2015 : analyse et réflexions.

The register of activity at the Ebola Treatment Center (ETC) in Forecariah (Guinea), from April 23 to June 5, 2015 is presented for analysis. The viral load of each patient is evaluated by the cycle threshold (Ct). One hundred and thirty patients were seen in Triage at the ETC, of which 24 (18.5%) patients who failed to meet theWHO case criteria for viral hemorrhagic fever were excluded from admission to the ETC. Of the 106 patients admitted in the ETC, 72 (67.9%) were declared non-cases after the results of their two PCR (drawn 48 hours apart) tests were negative. Thirty-four patients were tested positive for Ebola virus disease (EVD): 19 women and 15 men (sex ratio: male/female = 0.78), mean age of 33.51 ± 20.1 years (extremes of 42 days to 70 years), of which six children were aged below 8 years. The median initial Ct value was 21.6 ± 6.3 cycles in this group. Enquiry into patient contacts was only able to identify actual contacts in 20 of these patients (58.8%). Thirteen patients were ultimately cured of EVD (six men and seven women) - with a median age of 31.8 years (extremes of 4 to 54 years). These patients presented on admission with a median Ct value of 21.88 ± 6.2 cycles (extremes of 17.6 to 31.7). Of the six children aged below 8 years, only one survived. Twenty-one patients (61.76%) with EVD died (9 men and 12 women) - median age, 34 ± 21 years (extremes of 42 days to 70 years). They presented on admission with a median Ct value of 18 ± 7 cycles (extremes of 12 to 24). The single most important factor associated with lethality was the Ct value at the time of admission to the ETC (P = 0.0004), i.e., the lower the Ct value, the higher the lethality rate or simply stated, the higher the viral load, the greater the lethality. Age, sex, identification of contact, and delay between the onset of symptoms and admission did not prove to be predictive of death outcome in our series.

Renal neurogenic mediation of intracerebroventricular angiotensin II hypertension in rats raised on high sodium chloride diet.

Chronic elevation of sodium intake may affect the sensitivity of the central nervous system to intracerebroventricular (I.C.V.) angiotensin II (Ang II) infusion. Experiments were conducted to determine the influence of raising Sprague-Dawley rats from 2 to 3 weeks of age on low (5.0 mmol/L per kg food), normal (50 mmol/L per kg food), or high (250 mmol/L per kg food) NaCl diets on renal and cardiovascular responses to low-dose I.C.V. Ang II infusion. At 12 weeks of age, Sprague-Dawley rats were instrumented for chronic study, including brain lateral ventricular cannulation. Artificial cerebrospinal fluid was infused (0.25 microL/min I.C.V.) during control and recovery, whereas Ang II (20 ng/min) was infused for 5 days. During the experiment, respective sodium intakes were infused intravenously over 24 hours. In rats fed high sodium, control mean arterial pressure was 115+/-2 mm Hg and increased to 132+/-4 mm Hg by day 5 of I.C.V. Ang II infusion. This increase in arterial pressure was associated with significant (P<.05) decreases in sodium excretion, leading to the retention of 5.4+/-0.6 mmol/L total sodium over the 5 days of Ang II infusion. In rats raised on low and normal sodium intakes from weaning and in 10-week-old rats exposed to a high sodium diet for only 2 weeks, arterial pressure was not increased and sodium was not retained during I.C.V. Ang II infusion at 20 ng/min. In rats raised on the high sodium diet, bilateral renal denervation abolished the arterial hypertension and reduced the sodium retention over 5 days of I.C.V. Ang II infusion. Thus, chronic elevation of sodium intake increases the hypertensive response to low-dose I.C.V. Ang II infusion, which is dependent on intact renal nerves. We conclude that elevated postnatal NaCl intake enhances the pressor sensitivity of the brain to Ang II.

Comparison of hyperkalemic cardioplegia with altered [CaCl2] and [MgCl2] on [Ca2+]i transients and function after warm global ischemia in isolated hearts.

AIM: [MgCl(2)] and [CaCl(2)] may modify the cardioprotective effects of hyperkalemic cardioplegia (CP). We changed [MgCl(2)] and [CaCl(2)] in a CP solution to examine their effects on [Ca(2+)]i transients and cardiac function before and after global normothermic ischemia. METHODS: After stabilization and loading of indo 1-AM in Kreb's solution (KR), each heart was perfused with either KR or 1 of 4 CP solutions before 37 degrees C, 30 min ischemia followed by reperfusion with KR. The KR solution contained, in mM, 4.5 KCl, 2.4 MgCl(2) and 2.5 CaCl(2); the CP solutions had in addition to 18 KCl: CP 1 (control CP): 2.4 MgCl(2), 2.5 CaCl(2); CP 2: 7.2 MgCl(2), 2.5 CaCl(2); CP 3, 7.2 MgCl(2), 1.25 CaCl(2); CP 4: 2.4 MgCl(2), 1.25 CaCl(2). RESULTS: In the KR group [Ca(2+)]i markedly increased on early reperfusion while functional return (LVP, dLVP/dt((max and min))) was much reduced; each CP group led to reduced [Ca(2+)]i loading and improved function. The rates of cytosolic Ca(2+) fluxes (d[Ca(2+)]/dt(max) and d[Ca(2+)]/dt(min)) increased significantly compared to baseline in the KR group, but were mostly suppressed in the CP groups, and d[Ca(2+)]/dt(min) was lower after CP 4 compared to CP 1 on reperfusion. At 60 min reperfusion, LVP area to [Ca(2+)] area and cardiac efficiency to phasic [Ca(2+)] relationships were shifted after KR, but not after CP 1-4. With similar functional recovery, [Ca(2+)] transient and [Ca(2+)] area were significantly lower after CP 4 than after CP 1. CONCLUSION: Increasing [MgCl(2)] (CP 2 and 3) did not improve cardiac function or reduce Ca(2+) transients on reperfusion better than the other CP groups, but reducing [CaCl(2)] (CP 3 and 4) was more effective in reducing [Ca(2+)] transients on reperfusion after global ischemia.

A mechanistic mathematical model for the catalytic action of glutathione peroxidase.

Glutathione peroxidase (GPx) is a well-known seleno-enzyme that protects cells from oxidative stress (e.g., lipid peroxidation and oxidation of other cellular proteins and macromolecules), by catalyzing the reduction of harmful peroxides (e.g., hydrogen peroxide: H2O2) with reduced glutathione (GSH). However, the catalytic mechanism of GPx kinetics is not well characterized in terms of a mathematical model. We developed here a mechanistic mathematical model of GPx kinetics by considering a unified catalytic scheme and estimated the unknown model parameters based on different experimental data from the literature on the kinetics of the enzyme. The model predictions are consistent with the consensus that GPx operates via a ping-pong mechanism. The unified catalytic scheme proposed here for GPx kinetics clarifies various anomalies, such as what are the individual steps in the catalytic scheme by estimating their associated rate constant values and a plausible rationale for the contradicting experimental results. The developed model presents a unique opportunity to understand the effects of pH and product GSSG on the GPx activity under both physiological and pathophysiological conditions. Although model parameters related to the product GSSG were not identifiable due to lack of product-inhibition data, the preliminary model simulations with the assumed range of parameters show that the inhibition by the product GSSG is negligible, consistent with what is known in the literature. In addition, the model is able to simulate the bi-modal behavior of the GPx activity with respect to pH with the pH-range for maximal GPx activity decreasing significantly as the GSH levels decrease and H2O2 levels increase (characteristics of oxidative stress). The model provides a key component for an integrated model of H2O2 balance under normal and oxidative stress conditions.

Mitochondrial inner membrane electrophysiology assessed by rhodamine-123 transport and fluorescence.

Rhodamine-123 is widely used to make dynamic measurements of mitochondrial membrane potential both in vitro and in situ. Yet data interpretation is difficult due to a lack of quantitative understanding of how membrane potential and measured fluorescence are related. To develop such understanding, a model for dye transport across the mitochondrial inner membrane and partition into the membrane was developed. The model accounts for experimentally measured dye self-quenching and was integrated into a model of mitochondrial electrophysiology to estimate transients in mitochondrial membrane potential from kinetic fluorescence measurements. Our analysis indicates that (i) R123 fluorescence peaks at concentrations near 50 microM due to self-quenching; (ii) measured fluorescence intensity and membrane potential are related by a non-linear calibration curve sensitive to certain experimental details, including total concentration of dye and mitochondria in suspensions; and (iii) the time courses of membrane potential and electron transport fluxes following a perturbation (i.e. addition of ADP) significantly differ from observed transients in fluorescence intensity. These findings are consistent with the model predictions that mitochondria display a characteristic time of response to changes in substrate concentration of less than 0.1 s, corresponding to the time scale over which the rate of ATP synthesis changes to meet changes in ADP concentration.

Alpha-adrenergic systems mediate chronic central AII hypertension in rats fed high sodium chloride diet from weaning.

Hypertension is elicited by chronic, low dose intracerebroventricular (ICV) angiotensin II (AII) infusion in rats raised from weaning on relatively high sodium chloride diet (250 mEq kg(-1) food). This experimental model of hypertension is dependent upon renal innervation and associated with neurogenic sodium retention. The present study determined whether this neurogenic ICV AII hypertension is mediated by central alpha-adrenoceptors. Rats were weaned at 21 days of age and fed a 1.5% (250 mg kg(-1) food) sodium chloride diet for 10-12 weeks. At adulthood, animals were instrumented with central nervous system (CNS) lateral ventricular cannulas, femoral artery and vein catheters and housed in metabolic pens for chronic study. Low dose ICV AII infusion (20 ng min(-1)) increased mean arterial pressure (MAP) from 121 +/- 4 to 140 +/- 6 mm Hg on the day of ICV infusion. This increase in arterial pressure was associated with 3 consecutive days of decreased urinary sodium excretion. Subsequent ICV alpha-adrenoceptor blockade with phentolamine (AII + phentolamine) abolished the pressor and antinatriuretic responses to low dose chronic ICV AII infusion. Resumption of ICV AII infusion alone increased in MAP toward pre-alpha-adrenergic blockade values (133 +/- 5 mm Hg) on day 8. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly different from control. This model of hypertension was not dependent on circulating plasma renin activity (PRA), since PRA decreased during ICV AII infusion. These data confirm that low dose ICV AII causes hypertension and sodium retention in rats raised from weaning on moderately elevated sodium intake. We conclude that AII mediated neurogenic hypertension and antinatriuresis is elicited by stimulation of AT1 receptors on neurons which interact with noradrenergic cell bodies in cardiovascular and autonomic centers that may modulate renal sympathetic outflow via alpha-adrenoceptors.

Central AT1 and AT2 receptors mediate chronic intracerebroventricular angiotensin II-induced drinking in rats fed high sodium chloride diet from weaning.

Intracerebroventricular (ICV) angiotensin (AIl) administration stimulates central AII receptors to induce water consumption in rats. The aim of this study was to determine the role of brain AT1 and AT2 receptors in mediating chronic ICV AII-induced drinking in rats raised on normal or high sodium chloride diets from weaning. Rats were weaned at 21 days of age and placed on normal or high sodium chloride diet for 10-12 weeks. At adulthood, the animals were instrumented with brain lateral ventricular cannulas and femoral arterial catheters. Low dose chronic central AII infusion (20 ng min(-1)) significantly (P < 0.05) increased water intake in both groups of rats when compared with their respective controls of 24 h artificial cerebrospinal fluid infusions. In a separate group of high sodium fed rats, coinfusion of AII with the AT1 receptor antagonist, losartan (0.25 microg min(-1)) or the AT2 receptor blocker, PD 123319 (0.50 microg min(-1)) blocked chronic ICV AII-induced drinking. Upon reinfusion of AII water intake increased above control. Following the cessation of AII infusions, water intake returned to values not significantly different from control (P > 0.05). In contrast, in the normal sodium fed rats losartan, but not PD 123319, blocked the AII-mediated water intake. The data demonstrate that in high sodium chloride fed rats AII stimulates both central AT1 and AT2 receptors to induce drinking, while in the normal sodium chloride fed rats the peptide activates the drinking response primarily by stimulation of central AT1 receptors.

AT1 receptors mediate chronic central nervous system AII hypertension in rats fed high sodium chloride diet from weaning.

CNS angiotensin II (AII) hypertension is induced by chronic, low dose intracerebroventricular (ICV) AII infusion only in rats raised on a relatively high sodium chloride diet (250 meq kg(-1)food) from weaning. This experimental model of hypertension is dependent upon renal sympathetic innervation and associated with neurogenic sodium retention. This study determined whether AT1 and/or AT2 receptor subtypes in the CNS mediate this neurogenic ICV AII hypertension. Rats were weaned at 21 days of age and fed a 1.5% sodium chloride diet for 10-12 weeks. At adulthood, animals were instrumented with CNS lateral ventricular cannulas, femoral arterial and vein catheters and housed in metabolic pens for chronic study. Low dose ICV AII infusion (20 ng min(-1) )increased mean arterial pressure by 12+/-2 mm Hg and decreased urinary sodium excretion for three consecutive days. Subsequent ICV AT1 blockade with losartan abolished both the pressor and antinatriuretic responses to low dose ICV AII. In contrast, ICV AT2 receptor blockade with PD 123319 did not affect either angiotensin induced pressor or antinatriuretic responses. Following cessation of ICV AII infusion, arterial pressure and sodium excretion returned to values not significantly different from control in both groups of rats. These data confirm that low dose ICV AII causes hypertension and sodium retention in rats raised from early age on moderately elevated sodium intakes. This AII mediated neurogenic hypertension and antinatriuresis is transduced by activation of CNS AT1 receptors and not by activation of central AT2 receptors.

Interactions of halothane with isoproterenol and epinephrine on canine epicardial conduction velocity at normal and elevated potassium levels.

BACKGROUND: Halothane is known to potentiate catecholamine-induced depression of conduction velocity in Purkinje fibers but not endocardial muscle fibers. The purpose of this study was to examine the interactions of halothane with epinephrine and isoproterenol on canine epicardial conduction velocity at moderately elevated extracellular potassium concentration ([K]0). METHODS: Epicardial muscle strips (10x10x2 mm) were superfused with Tyrode's solution containing 4 or 8 mM [K]0 in the presence of 5 microM epinephrine or 1 microM isoproterenol with or without 0.8 mM halothane. Conduction velocity in the longitudinal and transverse directions relative to epicardial fiber orientation was recorded during alternate stimulation in each direction. RESULTS: In the presence of halothane, a change from 4 to 8 mM [K]0 decreased (P< or =0.05) longitudinal and transverse conduction velocities by 26% and 21%, respectively. Isoproterenol alone at 4 and 8 mM [K]0 depressed (P<0.05) both longitudinal and transverse conduction velocities. However, the depression of longitudinal conduction velocity by isoproterenol at 4 mM [K]0 was attenuated by halothane. Epinephrine with or without halothane depressed (P<0.05) both longitudinal and transverse conduction velocities at 8 but not at 4 mM [K]0. CONCLUSION: The results do not support a synergistic interaction between halothane and epinephrine on myocardial conduction but do demonstrate depression of conduction by epinephrine at 8 mM [K+]0, a potassium ion concentration comparable to those reported following epinephrine infusions.

Differential modulation of the cardiac L- and T-type calcium channel currents by isoflurane.

BACKGROUND: Volatile anesthetics exert their negative chronotropic and inotropic effects, in part by depressing the L- and T-type calcium channels. This study examines and compares the dose-dependent effects of isoflurane on atrial L- and T-type calcium currents (I(Ca,L) and I(Ca,T)) and ventricular I(Ca,L). METHODS: Whole cell I(Ca) was recorded from enzymatically isolated guinea pig cardiomyocytes. Current-voltage relations for atrial and ventricular I(Ca,L) was obtained from holding potentials of -90 and -50 mV to test a potential of +60 mV in 10-mV increments. Atrial I(Ca,T) was determined by subtraction of currents obtained from holding potentials of -50 and -90 mV. Steady state inactivation was determined using standard two-pulse protocols, and data were fitted with the Boltzmann equation. RESULTS: Isoflurane depressed I(Ca) in a dose-dependent manner, with Kd values of 0.23+/-0.03, 0.34+/-0.03, and 0.71+/-0.02 mM of anesthetic for atrial I(Ca,T) and I(Ca,L) and ventricular (ICa,L), respectively, and caused a significant (P < 0.05) hyperpolarizing shift in steady state inactivation. At 1.2 and 1.6 mm, isoflurane caused a significant (P < 0.05) depolarizing shift in the steady state activation in ventricular I(Ca,L) but not in atrial I(Ca,L) or I(Ca,T). In addition to the depression of I(Ca,L), isoflurane also induced a hyperpolarizing shift in the reversal potential of I(Ca) for both atrial and ventricular L-type calcium channels. CONCLUSION: The results show that atrial I(Ca,T) is more sensitive to isoflurane than atrial I(Ca,L), and ventricular I(Ca,L) was the least responsive to the anesthetic. These differential sensitivities of the calcium channels in the atrial and ventricular chambers might reflect phenotypic differences in the calcium channels or differences in modulation by the anesthetic.