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Lost circulation control remains a challenge in drilling operations. Self-healing gels, capable of self-healing in fractures and forming entire gel block, exhibit excellent resilience and erosion resistance, thus finding extensive studies in lost circulation control. In this study, layered double hydroxide, Acrylic acid, 2-Acrylamido-2-methylpropane sulfonic acid, and CaCl2 were employed to synthesize organic-inorganic nanocomposite gel with self-healing properties. The chemical properties of nanocomposite gels were characterized using X-ray diffraction, Fourier transform infrared spectroscopy, scanning electron microscope, X-ray photoelectron spectroscopy and thermogravimetric analysis. layered double hydroxide could be dispersed and exfoliated in the mixed solution of Acrylic acid and 2-Acrylamido-2-methylpropane sulfonic acid, and the swelling behavior, self-healing time, rheological properties, and mechanical performance of the nanocomposite gels were influenced by the addition of layered double hydroxide and Ca2+. Optimized nanocomposite gel AC6L3, at 90 °C, exhibits only a self-healing time of 3.5 h in bentonite mud, with a storage modulus of 4176 Pa, tensile strength of 6.02 kPa, and adhesive strength of 1.94 kPa. In comparison to conventional gel, the nanocomposite gel with self-healing capabilities demonstrated superior pressure-bearing capacity. Based on these characteristics, the nanocomposite gel proposed in this work hold promise as a candidate lost circulation material. [ABSTRACT FROM AUTHOR]

Arterial hypertension is the most common cardiovascular risk factor in the world. The prevalence of hypertension has doubled over the last 30 years. Despite the availability of many antihypertensive drugs, including angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs), the level of uncontrolled blood pressure (BP) in hypertensive patients remains very high, which contributes to the lack of optimization of cardiovascular risk. Antihypertensive treatment had cardioprotective effects [each reduction in systolic BP by 5 mm Hg reduced the risk of cardiovascular events in both primary and secondary cardiovascular disease (CVD) prevention by 9% and 11%, respectively]. The reasons for the lack of BP control are lack of adherence and persistence in treatment, as well as therapeutic inertia. Therefore, new therapeutic options are being sought to improve BP control. Zilebesiran, the first drug based on small interference RNA (siRNA) technology for the treatment of hypertension, is currently being tested in randomized clinical trials (KARDIA-2; KARDIA-3). The results of the phase 1 study showed that zilebesiran in a single dose allowed for a sustained reduction in systolic BP by 22 mm Hg and diastolic BP by 10 mm Hg for as long as 6 months. This effect is related to this drug's unique mechanism of action -- silencing of the angiotensinogen (AGT) gene in the liver. Zilebesiran reduces serum AGT levels by > 90%. In clinical trials, this drug had a satisfactory safety profile and was well tolerated by patients. The use of drugs that need to be taken less frequently contributed to a significant improvement in compliance with medical recommendations in patients with lipid disorders. Therefore, it is expected that using zilebesiran only twice a year would improve compliance with medical recommendations (adherence and persistence) and contribute to improved BP control in patients with hypertension. This article summarizes information on the mechanism of action, effectiveness, and safety of zilebesiran and presents the most important arguments indicating the need to introduce this drug into clinical practice. [ABSTRACT FROM AUTHOR]

The concept that hypertension is vascular inflammation has been widely recognized. A large number of experiments have been carried out in the past, but no relevant breakthroughs have been made in clinical application. At present, the drugs for clinical treatment of hypertension still take the previous pathogenesis of hypertension as the target, so the treatment of hypertension has not achieved satisfactory results. This article starts from the relationship between hypertension and inflammatory response, and integrates relevant research on the treatment of hypertension and inflammatory response by Chinese and Western medicine in the past three years, with a view to providing new directions and targets for the prevention and treatment of hypertension, so as to better control hypertension and Target organ damage. [ABSTRACT FROM AUTHOR]

Aims The Hygia Chronotherapy Trial, conducted within the clinical primary care setting, was designed to test whether bedtime in comparison to usual upon awakening hypertension therapy exerts better cardiovascular disease (CVD) risk reduction. Methods and results In this multicentre, controlled, prospective endpoint trial, 19 084 hypertensive patients (10 614 men/8470 women, 60.5 ± 13.7 years of age) were assigned (1:1) to ingest the entire daily dose of ≥1 hypertension medications at bedtime (n  = 9552) or all of them upon awakening (n  = 9532). At inclusion and at every scheduled clinic visit (at least annually) throughout follow-up, ambulatory blood pressure (ABP) monitoring was performed for 48 h. During the 6.3-year median patient follow-up, 1752 participants experienced the primary CVD outcome (CVD death, myocardial infarction, coronary revascularization, heart failure, or stroke). Patients of the bedtime, compared with the upon-waking, treatment-time regimen showed significantly lower hazard ratio—adjusted for significant influential characteristics of age, sex, type 2 diabetes, chronic kidney disease, smoking, HDL cholesterol, asleep systolic blood pressure (BP) mean, sleep-time relative systolic BP decline, and previous CVD event—of the primary CVD outcome [0.55 (95% CI 0.50–0.61), P  < 0.001] and each of its single components (P  < 0.001 in all cases), i.e. CVD death [0.44 (0.34–0.56)], myocardial infarction [0.66 (0.52–0.84)], coronary revascularization [0.60 (0.47–0.75)], heart failure [0.58 (0.49–0.70)], and stroke [0.51 (0.41–0.63)]. Conclusion Routine ingestion by hypertensive patients of ≥1 prescribed BP-lowering medications at bedtime, as opposed to upon waking, results in improved ABP control (significantly enhanced decrease in asleep BP and increased sleep-time relative BP decline, i.e. BP dipping) and, most importantly, markedly diminished occurrence of major CVD events. Trial registration ClinicalTrials.gov, number NCT00741585.   Open in new tab Download slide Open in new tab Download slide [ABSTRACT FROM AUTHOR]

Objective: To observe the clinical effect of Banxia Atractylodes macrocephala Tianma decoction in the treatment of hypertension. Methods: A total of 100 patients with hypertension were selected from our hospital (April 2016 to July 2019) and divided into 2 groups by random digital method. The control group was given routine symptomatic treatment of western medicine, and the observation group was given Banxia Atractylodes Gastrodia decoction on the basis of the control group. the levels of syndrome score and adiponectin (apn), cysc (cysc), uric acid (ua), c-reactive protein (crp), superoxide dismutase (sod), malondialdehyde (mda),8- hydroxydeoxyguanylic acid (8-ohdg) were recorded before and after treatment in group 2, and the total effective rate of clinical treatment was counted in group 2. Results: After treatment, the total effective rate (92.00%) in the observation group was higher than that in the control group (74.00%), and the difference was statistically significant (P<0.05). The APNSOD level of the observation group was higher than that of the control group after treatment, and the CysCUACRPMDA8-OHdG level and TCM symptom score were lower than those of the control group (P<0.05). Conclusion: Rhizoma Pinelliae and Rhizoma Gastrodiae decoction for treating hypertension can relieve oxidative stress injury, adjust the expression level of APN, CysC, CRP and UA, and improve the symptoms and improve the curative effect. [ABSTRACT FROM AUTHOR]

Tanshinone ⅡA Sodium Sulfonate (DS-201), a derivative of traditional Chinese medicinal herb Danshen, has been clinically used for various cardiovascular diseases. Previous studies showed that DS-201 induced vascular relaxation partly due to the activation of the large conductance Ca2+-activated potassium (BK Ca) channels. However, the efficacy of DS-201 on the resistant vessels in hypertension remains unknown. Mesentery arteries obtained from spontaneously hypertensive rats (SHR) and hypertension patients were used in this study. The endothelium-denuded mesenteric arteries were prepared to measure the artery tension and evaluate the vasodilatory effect of DS-201. The results showed that DS-201 had a vasodilatory effect on the mesenteric artery rings pre-contracted with either phenylephrine (PE) or thromboxane mimetic U46619 in a concentration-dependent manner. However, the vasodilatory effect of DS-201 significantly decreased in hypertension than in control arteries due to a decrease in protein level of BK Ca β1subunit. A BK Ca channel blocker IbTX (200 nM) significantly inhibited the relaxant effect of DS-201 on non-hypertensive arteries, whereas the BK Ca channel specific agonist NS1619 rescued the vasodilating effects of DS-201 on hypertensive vessels. These results indicate that the vasodilating effect of DS-201 is BK Ca -dependent. This study demonstrated that DS-201 alone may not be effective for treating hypertension, but it may be considered as therapy combined with BK Ca -agonists or methods rescuing BK Ca functions. [ABSTRACT FROM AUTHOR]

Abstract: The use of implants made out of metallic materials can cause some negative effects that reduce the effectiveness of treatment of various diseases of the human circulatory system. These include, above all, blood clotting on the surface and insufficient hemocompatibility [1]. To reduce these negative effects, the formation of physical and chemical properties of the surface layer of the implants are indicated [2]. The paper proposes the use of the atomic layer deposition method to form a surface layer with participation of a suitable silicon morphology. One of the basic criteria of hemocompatibility of implants is their corrosion resistance. Therefore, in assessing the SiO2 layer, a detailed test for resistance to corrosion by potentiodynamic and impedance studies were conducted, including the process of steam sterilization under pressure. The chemical structure of the surface layer was also evaluated. The results clearly demonstrated that the applied layer of SiO2 has better corrosion resistance when compared to the steel substrate. This reduces excessive transfer of iron, chromium, nickel and molybdenum into the blood. On the other hand, studies of the chemical composition of the depth profile showed a diffuse SiO2 layer which results in a better adhesion to the substrate. [ABSTRACT FROM AUTHOR]

In view of the blood circulation network model that reflects the system performance with difficulty. According to blood circulation network branch flowquantity and pressure mutual influence hemodynamic characteristic, utilize Kirchhoff's current and voltage laws, graph theoretic concepts and hemodynamic equations of individual branches, establishes the multivariable nonlinear minimal model. Decentralized and adaptive controller design based on the minimal model, we solve a decentralized and adaptive nonlinear control problem where actuator valves and flowrate sensors are collocated in individual branches and do not exchange information. We solve the tracking (time varying reference signals) problems. Through cerebral circulation network simulation, it can realize the control process from pathology to normal, provides the basic theories to treatment and method of the diseases about the cerebral circulation. [ABSTRACT FROM AUTHOR]

Despite advancements in hypertensive therapies, the prevalence of hypertension and associated morbidities are still immense. Physicians are in great need for updated information on novel and effective antihypertensive therapies. Therefore, the study objective was to provide comprehensive information on the efficacy of available antihypertensive therapies. Antihypertensive therapies were divided into four general approaches: diet, nutritional supplements, lifestyle modification, and conventional antihypertensive medications. A search of PubMed and Google Scholar resulted in an analysis of 30 antihypertensive therapies from meta-analyses and randomized-controlled trials (RCTs). The studies were analyzed using the American Heart Association/American College of Cardiology classification system. Calculated average blood pressure reductions were: (systolic/diastolic) 6/4 mmHg, 4/2 mmHg, 5/3 mmHg, and 9/5 mmHg for dietary, nutritional supplements, lifestyle, and medications, respectively. The results demonstrate that dietary, nutritional supplement and lifestyle strategies have a solid level of evidence to support their efficacy as antihypertensive strategies. These strategies can be as effective as medications and, in some cases, even more effective. Dissemination of this information to physicians/dietitians can help facilitate an important shift in hypertension management. [ABSTRACT FROM AUTHOR]

Recently, we have established a model of severe stepwise normovolemic hemodilution to a hematocrit of 10 % in rats employing three different colloidal volume replacement solutions (Voluven, Volulyte and Gelafundin) that are routinely used in clinical practice at present. We did not see severe dilutional acidosis as to be expected, but a decline in urinary pH. We here looked on further mechanisms of renal acid excretion during normovolemic hemodilution. Bicarbonate, which had been removed during normovolemic hemodilution, was calculated with the help of the Henderson-Hasselbalch equation. The urinary amount of ammonium as well as phosphate was determined in residual probes. The absolute amount of free protons in urine was obtained from the pH of the respective samples. The amount of protons generated during normovolemic hemodilution was approximately 0.6 mmol. During experimental time (5.5 h), distinct urinary ammonium excretion occurred (Voluven 0.52 mmol, Volulyte 0.39 mmol and Gelafundin 0.77 mmol). Proton excretion via the phosphate buffer constituted 0.04 mmol in every experimental group. Excretion of free protons was in the range of 10-6 mmol. The present data prove that the prompt rise in urinary ammonium excretion is also valid for acute metabolic acidosis originating from severe normovolemic hemodilution. [ABSTRACT FROM AUTHOR]

Traditional Chinese medicine has been used to treat a variety of human diseases for many centuries. Zanthoxylum nitidum var. tomentosum is used as an adjuvant to promote blood circulation and remove stasis. However, the mechanisms of improving circulation and other biological activities of Z. nitidum var. tomentosum are still unclear. Plasminogen activator inhibitor-1 (PAI-1) regulates the plasminogen activation system through inhibition of tissue-type and urokinase-type plasminogen activators (tPA and uPA). PAI-1 has been linked to fibrin deposition that evolves into organ fibrosis and atherosclerosis. In the present study, we showed that ethanol extract prepared from Z. nitidum var. tomentosum exhibited PAI-1 inhibitory activity, and identified toddalolactone as the main active component that inhibited the activity of recombinant human PAI-1 with IC50 value of 37.31 ± 3.23 µM, as determined by chromogenic assay, and the effect was further confirmed by clot lysis assay. In vitro study showed that toddalolactone inhibited the binding between PAI-1 and uPA, and therefore prevented the formation of the PAI-1/uPA complex. Intraperitoneal injection of toddalolactone in mice significantly prolonged tail bleeding and reduced arterial thrombus weight in a FeCl3-induced thrombosis model. In addition, the hydroxyproline level in the plasma and the degree of liver fibrosis in mice were decreased after intraperitoneal injection of toddalolactone in CCl4-induced mouse liver fibrosis model. Taken together, PAI-1 inhibition exerted by toddalolactone may represent a novel molecular mechanism by which Z. nitidum var. tomentosum manifests its effect in the treatment of thrombosis and fibrosis. [ABSTRACT FROM AUTHOR]

Background: Anticoagulants have been used in the treatment of several circulatory diseases and thrombotic disorders, and in the blood sampling for hematologic analysis. Sulfated polysaccharides (SP), which have anticoagulant properties, are found in most seaweeds, including Caulerpa spp. Objective: The study generally aimed to evaluate the potential anticoagulant property of Caulerpa lentillifera. Methodology: The whole plant of fresh C. lentillifera was washed thoroughly with distilled water and manually expressed to obtain the extract. C. lentillifera extract was tested in two phases. Phase one utilized nine male albino rabbits, which were randomly and equally allocated into three groups: (1) negative control (oral distilled water and subsequent in vitro mixing of extracted blood with normal saline solution), (2) positive control (oral aspirin and subsequent in vitro mixing of extracted blood with normal saline solution), and (3) experimental group (oral distilled water and in vitro mixing of extracted blood with C. lentillifera extract). Blood coagulation was evaluated by measuring the clotting time using the slide and tube methods. In phase two, peripheral blood from three apparently healthy adult dogs were used. Blood collection was performed thrice. In each collection, the sample was divided into five aliquots: (1) negative control (normal saline solution), (2) positive control (ethylenediaminetetraacetic acid [EDTA]), and (3-5) experimental treatments at 0.1, 0.15, and 0.2 ml of C. lentillifera extract. Coagulation was evaluated by measuring the clotting time using the tube method. Results: Phase one results revealed significant differences on the clotting time between the negative and the positive and experimental groups (P < 0.05), and no significant differences on the clotting time between the positive and the experimental groups (P > 0.05). In phase two, all blood samples mixed with EDTA did not clot, while the negative control had an average clotting time of 2.01 min. Blood mixed with 0.2 ml of C. lentillifera extract had the longest coagulation time (15.49 min). Simple linear regression revealed a positive significant correlation (multiple R = 0.9450, R2 = 0.8931, P = 0.02) implying dose-dependent anticoagulant potential. The study showed that C. lentillifera extract may have a potential anticoagulant property due to its component SP. [ABSTRACT FROM AUTHOR]

Chronic wounds, especially in diabetic patients, represent a challenging health issue. Since standard treatment protocols often do not provide satisfactory results, additional treatment methods-like phototherapy using low-level light therapy-are being investigated. The aim of our study was to evaluate the effect of phototherapy with light-emitting diodes on chronic wound treatment in diabetic and non-diabetic patients. Since a sufficient blood supply is mandatory for wound healing, the evaluation of microcirculation in the healthy skin at a wound's edge was the main outcome measure. Forty non-diabetic patients and 39 diabetics with lower limb chronic wounds who were referred to the University Medical Center Ljubljana between October 2012 and June 2014 were randomized to the treated and control groups. The treated group received phototherapy with LED 2.4 J/cm2 (wavelengths 625, 660, 850 nm) three times a week for 8 weeks, and the control group received phototherapy with broadband 580-900 nm and power density 0.72 J/cm2. Microcirculation was measured using laser Doppler. A significant increase in blood flow was noted in the treated group of diabetic and non-diabetic patients (p = 0.040 and p = 0.033), while there was no difference in the control groups. Additional Falanga wound bed score evaluation showed a significant improvement in both treated groups as compared to the control group. According to our results, phototherapy with LED was shown to be an effective additional treatment method for chronic wounds in diabetic and non-diabetic patients. [ABSTRACT FROM AUTHOR]

Purpose: Up to 53% of cardiac surgery patients experience postoperative neurocognitive decline. Cerebral oximetry is designed to detect changes in cerebral tissue saturation and therefore may be useful to predict which patients are at risk of developing neurocognitive decline.Methods: This is a retrospective analysis of a prospective study originally designed to determine if treatment of cerebral oximetry desaturation is associated with improvement in postoperative cognitive dysfunction in patients undergoing aortic reconstruction under deep hypothermic circulatory arrest. Cognitive function was measured, preoperatively and 3 months postoperatively, with 15 neuropsychologic tests administered by a psychologist; the individual test scores were summed and normalized. Bilateral cerebral oximetry data were stored and analyzed using measures of entropy. Cognitive decline was defined as any decrease in the summed normalized score from baseline to 3 months.Results: Seven of 17 (41%) patients suffered cognitive decline. There was no association between baseline cerebral oximetry and postoperative cognitive dysfunction. Nor were changes in oximetry values associated with cognitive decline. However, cognitive decline was associated with loss of forbidden word entropy (FwEn) (correlation: Rho ρ = 0.51, P = 0.037 for left cerebral oximetry FwEn and ρ = 0.54, P = 0.025 for right cerebral oximetry FwEn).Conclusion: Postoperative cognitive decline was associated with loss of complexity of the time series as shown by a decrease in FwEn from beginning to end of the case. This suggests that regulation of cerebral oximetry is different between those who do and those who do not develop cognitive decline. [ABSTRACT FROM AUTHOR]

Objectives: Stroke volume variation and pulse pressure variation do not reliably predict fluid responsiveness during low tidal volume ventilation. We hypothesized that with transient increase in tidal volume from 6 to 8 mL/kg predicted body weight, that is, "tidal volume challenge," the changes in pulse pressure variation and stroke volume variation will predict fluid responsiveness.Design: Prospective, single-arm study.Setting: Medical-surgical ICU in a university hospital.Patients: Adult patients with acute circulatory failure, having continuous cardiac output monitoring, and receiving controlled low tidal volume ventilation.Interventions: The pulse pressure variation, stroke volume variation, and cardiac index were recorded at tidal volume 6 mL/kg predicted body weight and 1 minute after the "tidal volume challenge." The tidal volume was reduced back to 6 mL/kg predicted body weight, and a fluid bolus was given to identify fluid responders (increase in cardiac index > 15%). The end-expiratory occlusion test was performed at tidal volumes 6 and 8 mL/kg predicted body weight and after reducing tidal volume back to 6 mL/kg predicted body weight.Results: Thirty measurements were obtained in 20 patients. The absolute change in pulse pressure variation and stroke volume variation after increasing tidal volume from 6 to 8 mL/kg predicted body weight predicted fluid responsiveness with areas under the receiver operating characteristic curves (with 95% CIs) being 0.99 (0.98-1.00) and 0.97 (0.92-1.00), respectively. The best cutoff values of the absolute change in pulse pressure variation and stroke volume variation after increasing tidal volume from 6 to 8 mL/kg predicted body weight were 3.5% and 2.5%, respectively. The pulse pressure variation, stroke volume variation, central venous pressure, and end-expiratory occlusion test obtained during tidal volume 6 mL/kg predicted body weight did not predict fluid responsiveness.Conclusions: The changes in pulse pressure variation or stroke volume variation obtained by transiently increasing tidal volume (tidal volume challenge) are superior to pulse pressure variation and stroke volume variation in predicting fluid responsiveness during low tidal volume ventilation. [ABSTRACT FROM AUTHOR]

Percutaneous therapies for peripheral artery disease continue to evolve with new techniques and devices. Although guidelines-recommended therapies have impacted cardiovascular morbidity and mortality, endovascular interventions have been shown to reduce limb pain, improve quality of life, and prolong walking distance for those with claudication and to reduce amputation rates among those with critical limb ischemia. Novel devices such as drug-eluting stents and drug-coated balloons have improved patency for moderate-length lesions, whereas others allow treatment of heavily calcified and tortuous segments. New adjunctive devices to cross lesions and reduce or modify associated plaque have also been developed, although level 1 data regarding their efficacy are sparse. There has also been a better mechanistic understanding of lower extremity endovascular treatment using tools such as intravascular ultrasound. This information has highlighted the need for better stent size selection for the femoropopliteal arterial segments and larger balloon diameters for the tibial arteries. Moreover, a wound perfusion approach with direct in-line flow, the so-called angiosome approach, and reconstruction of the pedal loop have been advocated for improved wound healing. Technical advances such as the tibiopedal access and reentry methods have allowed crossing of lesions that were considered no option for the endovascular approach in the past. Collectively, there has been increased awareness, interest, and commitment by various specialty societies and organizations to advance the treatment of peripheral artery disease and critical limb ischemia. This is also evident by the recent coalition of 7 professional societies and organizations that represented >150 000 allied health professionals and millions of patients with peripheral artery disease at the 2015 Centers for Medicaid and Medicare Services Medicare Evidence Development and Coverage Analysis Committee meeting. The percutaneous therapies for peripheral artery disease continue to evolve with longer follow-up with randomized data and larger prospective registries. In the future, it is hopeful that we will treat the lower extremity arteries according to segments, taking into account plaque morphology, luminal versus subintimal crossing, location, and stenotic versus occlusive disease. Until then, we must identify the most cost-effective, efficacious, and safe treatment for each patient. The goal of this article is to aid the practicing vascular specialist consider the optimal choices for the management of patients with vascular disease. [ABSTRACT FROM AUTHOR]

Background: Large-volume total paracentesis may result in paracentesis-induced circulatory dysfunction, which is associated with poor outcomes.Aims: To explore the short- and long-term effects of paracentesis-induced circulatory dysfunction on systemic hemodynamics, renal function and other cirrhosis-related complications in patients with refractory ascites, following subtotal large-volume paracentesis.Methods: Patients with cirrhosis and refractory ascites without renal dysfunction had systemic hemodynamics, renal function, and neurohormones (plasma active renin, aldosterone, norepinephrine and angiotensin II) measured pre- and 6 days post-paracentesis. Paracentesis was limited to ≤8 L with 6-8 g of albumin per liter ascites drained. Patients were followed up until transjugular intrahepatic portosystemic shunt insertion, liver transplantation, or death. Paracentesis-induced circulatory dysfunction was defined as >50 % increase in plasma active renin 6 days post-paracentesis.Results: Fifty-seven patients (mean age 59.0 ± 9.4 years) had mean 6.8 ± 1.8 L of ascites removed with 9 ± 3 g of albumin given/L of ascites drained. Patients were followed up for 715 ± 104 days. Twenty-three patients (40.4 %) developed paracentesis-induced circulatory dysfunction with unchanged serum creatinine on day six, despite worsening of hemodynamics (mean arterial pressure 90 ± 10 mmHg at baseline vs. 84 ± 8 mmHg on day six, p < 0.05). Similar hemodynamic changes were observed among patients without paracentesis-induced circulatory dysfunction. There was no significant difference in the long-term renal function or cirrhosis-related complications between the groups.Conclusion: The occurrence of paracentesis-induced circulatory dysfunction, as defined by plasma active renin, may not have a significant short- and long-term impact on renal function or cirrhosis-related complications in patients with refractory ascites who undergo subtotal paracentesis with albumin infusion. [ABSTRACT FROM AUTHOR]

Background Several methods have been postulated for the treatment of acute on chronic lower limb ischemia; among them, the hybrid procedure (combined open thrombectomy and angioplasty) is gaining popularity. It is aimed at clearing the vessel and treating the underlying vessel lesion in one step. Patients and methods A total of 23 patients admitted to the vascular department were eligible for inclusion in this study. They were subjected to thromboembolectomy, followed by endovascular balloon dilatation with or without stenting. Data regarding the risk factors, procedure success, and complications were recorded. Results Hybrid procedures showed 83% immediate technical success and 74% primary limb salvage rate up to 1 month with no early complications. Infrapopliteal lesions were the most difficult to treat and the leading cause of limb loss. Conclusion The hybrid procedure provides an accepted outcome in treating immediately limbthreatening acute on chronic lower limb ischemia. [ABSTRACT FROM AUTHOR]

The article presents the study that investigates the changes in oral anticoagulants (OACs) in atrial fibrillation-diagnosed patients in Taiwan. The topics discussed include the effectiveness of warfarin and OAC combination in preventing stroke, the comparison between nonvitamin K antagonist OAC and warfarin, and the statistics showing the estimated number of patients who are at risk of the ischemic stroke.

An intravascular axial flow pump is being developed as a mechanical cavopulmonary assist device for adolescent and adult patients with dysfunctional Fontan physiology. Coupling computational modeling with experimental evaluation of prototypic designs, this study examined the hydraulic performance of 11 impeller prototypes with blade stagger or twist angles varying from 100 to 600 degrees. A refined range of twisted blade angles between 300 and 400 degrees with 20-degree increments was then selected, and four additional geometries were constructed and hydraulically evaluated. The prototypes met performance expectations and produced 3-31 mm Hg for flow rates of 1-5 L/min for 6000-8000 rpm. A regression analysis was completed with all characteristic coefficients contributing significantly ( P < 0.0001). This analysis revealed that the impeller with 400 degrees of blade twist outperformed the other designs. The findings of the numerical model for 300-degree twisted case and the experimental results deviated within approximately 20%. In an effort to simplify the impeller geometry, this work advanced the design of this intravascular cavopulmonary assist device closer to preclinical animal testing. [ABSTRACT FROM AUTHOR]

Several techniques for surgical treatment of acute or subacute left ventricular free wall rupture (LVFWR) have been described using a sutured or sutureless patch with different currently available materials. We present a case report of a 50-year-old male with acute LVFWR, who was treated with a simple surgical technique using an 'off-pump' epicardially sutured LV patch consisting of an acellular xenogeneic extracellular matrix (ECM). ECM patches are structurally more surgeon-friendly and have shown to be bioactive, and capable of activating remodelling and even tissue regeneration. Compared with conventional pericardial patches, the advantage of this material is excellent pliability and very easy stitching owing to the thin composition of the material. In addition, and most importantly, in case of complex structural reconstructions, the patch is highly tear-proof. [ABSTRACT FROM AUTHOR]

OBJECTIVES: Remote ischaemic preconditioning (RIPC) is a non-invasive and virtually cost-free strategy for protecting the heart against acute ischaemia-reperfusion injury (IRI). We have recently shown that the inhibition of extracellular RNA (eRNA) using non-toxic RNase1 protected the heart against acute IRI, reduced myocardial infarct (MI) size and preserved left ventricular systolic function in rodent animal MI models. Based on this previous work in animals, the role of the eRNA/RNase1 system in cardiac RIPC in humans should be defined. METHODS: Fourteen patients underwent cardiac surgery without RIPC; from each patient, six separate 5 ml blood specimens from radial artery and two blood specimens from coronary sinus at different time points during heart surgery were taken. Six healthy donors received RIPC (4 × 5 min upper limb ischaemia); blood parameters were quantified before and after RIPC. Twelve patients underwent cardiac surgery of which 6 received RIPC, whereas the remaining 6 were exposed to sham procedure. Circulating eRNA was quantified in plasma from arterial and coronary sinus blood obtained from patients undergoing cardiac by standard procedures. Tumour necrosis factor-α (TNF-α) production by heart tissue was assessed by enzyme-linked immuno-sorbent assay; RNase activity was quantified by an enzymatic assay. RESULTS: Before surgery, eRNA levels were similar in both groups (14 ± 6 vs 13 ± 5 ng/ml; P = 0.9967). In patients without RIPC, arterial eRNA levels rose during surgery (87 ± 12 ng/ml) and peaked after (127 ± 11 ng/ml) aortic declamping; accordingly, eRNA levels in coronary sinus blood were significantly higher (206 ± 32 ng/ml; P = 0.0129) than that in radial artery. Moreover, significant elevation of TNF-α (36 ± 6 ng/ml; P = 0.0059) particularly in coronary sinus blood after opening of the aortic clamping was observed. Interestingly, applying a RIPC protocol significantly increased levels of plasma endogenous vascular RNase1 by >7-fold, and the levels of arterial (31 ± 7 ng/ml; P = 0.0024) and coronary sinus (37 ± 9 ng/ml; P < 0.0001) circulating eRNA, as well as circulating TNF-α (20 ± 4 ng/ml; P = 0.0050) levels were significantly reduced. CONCLUSIONS: Upon RIPC, the level of cardioprotective RNase1 increased, while the concentration of damaging eRNA and TNF-α decreased. The present findings imply a significant contribution of the RIPC-dependent (endothelial) RNase1 for improving the outcome of cardiac surgery. However, the exact mechanism of RNase1-induced cardioprotection still remains to be explored. [ABSTRACT FROM AUTHOR]

BACKGROUND: Only half of hypertensive adults achieve blood pressure (BP) control in the United States, and it is unclear how BP control rates may be improved most effectively and efficiently at the population level. OBJECTIVE: We sought to compare the potential effects of system-wide isolated improvements in medication adherence, visit frequency, and higher physician prescription rate on achieving BP control at 52 weeks. DESIGN: We developed a Markov microsimulation model of patient-level, physician-level, and system-level processes involved in controlling hypertension with medications. The model is informed by data from national surveys, cohort studies and trials, and was validated against two multicenter clinical trials (ALLHAT and VALUE). SUBJECTS: We studied a simulated, nationally representative cohort of patients with diagnosed but uncontrolled hypertension with a usual source of care. INTERVENTIONS: We simulated a base case and improvements of 10 and 50 %, and an ideal scenario for three modifiable parameters: visit frequency, treatment intensification, and medication adherence. Ideal scenarios were defined as 100 % for treatment intensification and adherence, and return visits occurring within 4 weeks of an elevated office systolic BP. MAIN OUTCOME: BP control at 52 weeks of follow-up was examined. RESULTS: Among 25,000 hypothetical adult patients with uncontrolled hypertension (systolic BP ≥ 140 mmHg), only 18 % achieved BP control after 52 weeks using base-case assumptions. With 10/50 %/idealized enhancements in each isolated parameter, enhanced treatment intensification achieved the greatest BP control (19/23/71 %), compared with enhanced visit frequency (19/21/35 %) and medication adherence (19/23/26 %). When all three processes were idealized, the model predicted a BP control rate of 95 % at 52 weeks. CONCLUSION: Substantial improvements in BP control can only be achieved through major improvements in processes of care. Healthcare systems may achieve greater success by increasing the frequency of clinical encounters and improving physicians' prescribing behavior than by attempting to improve patient adherence to medications. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Can bilateral renal denervation, an effective antihypertensive treatment in clinical and experimental studies, improve cardiac β-adrenoceptor responsiveness in a diabetic model with underlying hypertension?, What is the main finding and its importance? Bilateral renal denervation did not affect β-adrenergic responsiveness in the diabetic hypertensive rat heart, but denervation reduced the hypertension-induced concentric hypertrophic remodelling. This suggests that the positive haemodynamic changes induced by renal denervation are most likely to reflect an attenuation of sympathetic effects on the systemic vasculature and/or the renal function rather than direct sympathetic modulation of the heart., Bilateral renal denervation (BRD) has been shown to normalise blood pressure in clinical and experimental studies of hypertension by reducing systemic sympathetic output. This study determined the effect of BRD on cardiac β-adrenoceptor (AR) responsiveness in a diabetic model with underlying hypertension using the transgenic (mRen-2)27 rats. Bilateral renal denervation or sham surgeries were conducted repeatedly at 3, 6 and 9 weeks in Ren-2 rats with or without streptozotocin (STZ)-induced diabetes (4 × n = 7); Sprague-Dawley rats ( n = 6) served as control animals. Cardiac function was determined in isolated hearts at 18 weeks of age. Normalised left ventricular developed pressure and relaxation was recorded in response to incremental concentrations of the β-AR agonist isoprenaline (from 10−10 to 10−7 m) or the β3-AR agonist BRL37344 (from 10−13 to 10−6 m). Expression levels of β1-AR were determined by Western blot. Both inotropic and lusitropic β-AR responsiveness was reduced in the hypertensive diabetic hearts, but these responses were unaltered after BRD. Expression levels of β1-AR were increased after BRD (Sham, 0.85 ± 0.11 versus 1.01 ± 0.05 a.u.; BRD, 1.45 ± 0.11 versus 1.46 ± 0.07 a.u.; Ren-2 versus Ren-2 STZ, P < 0.05 versus Sham). No effect of β3-AR agonist stimulation with BRL37344 was observed. Interestingly, BRD increased left ventricular diastolic volume in both the Ren-2 and the Ren-2 STZ groups. Bilateral renal denervation did not restore the attenuated cardiac β-AR responsiveness in the diabetic hypertensive rats, but it reduced the extent of hypertension-induced concentric hypertrophic remodelling. Thus, the haemodynamic protection offered by renal denervation appears to reflect an attenuated sympathetic innervation of the systemic vasculature and/or kidney rather than a direct cardiac effect. [ABSTRACT FROM AUTHOR]

Objective: The objective was to investigate the endothelial nitric oxide synthase (eNOS/NO) pathway is involved or not in the protective effects of glycyrrhizic, ferulic, paeoniflorin, cinnamic (GFPC) in myocardial ischemia-reperfusion injury Sprague-Dawley rats. Materials and Methods: Ischemia-reperfusion (I/R) model was made by ligating the left anterior descending branch of the coronary artery for 30 min and releasing for 120 min, then the left ventricular apical was fixed and sliced, morphological changes of myocardial microvascular endothelial cell (MMVEC) was observed by electron microscopy, apoptosis index of MMVEC was observed by means of TUNEL, serum NO was tested by methods of nitrate reduction, lactate dehydrogenase (LDH), creatine kinase MB (CK-MB) was detected by automatic biochemical analyzer; Phosphorylated eNOS (PeNOS) and inducible NOS (iNOS) protein were measured by means of western blot. Results: In positive product control group, the serum levels of NO, LDH, CK-MB significantly increased (P < 0.05); MMVEC apoptosis was significantly decreased (P < 0.05); incidence of area at risk decreased significantly (P < 0.05); PeNOS protein increased (P < 0.05); iNOS protein decreased significantly (P < 0.05). Conclusion: Ischemic preconditioning of GFPC from GFPC plays a protective role in I/R heart through regulating the eNOS/NO signal pathway by increasing the PeNOS protein expression and decreasing the expression of iNOS protein. [ABSTRACT FROM AUTHOR]

Antiplatelet therapy (AT) is indicated in hypertensive patients with increased cardiovascular risk. The literature about the adequate or inadequate prescription of AT is scarce. We conducted a prospective descriptive study to quantify therapeutic inertia and non-guideline-recommended prescription (NGRP) of AT (aspirinor clopidogrel or both), and to assess associated factors, calculating the adjusted odds ratios (ORs) from multivariate models. In 2007-2009, 712 primary health-care hypertensive patients in a Spanish region were enrolled. Inertia was defined as the lack of an AT prescription, despite being indicated by guidelines, whereas NGRP was defined as AT prescription when there was no guideline recommendation. We also recorded cardiovascular variables. Inertia and NGRP were quantified for primary and secondary prevention. Of 108 patients in secondary prevention, 53 had inertia (49.1%, 95% confidence interval (CI): 39.6-58.5%). Associated profile: female (OR=0.460, P=0.091), no dyslipidemia (OR=0.393, P=0.048), no coronary heart disease (OR=0.215, P=0.001) and high diastolic blood pressure (OR=1.076, P=0.016). In primary prevention, NGRP was present in 69 of 595 patients (11.6%, 95% CI: 9.0-14.2%). Associated profile: male (OR=1.610, P=0.089), smoking (OR=2.055, P=0.045), dyslipidemia (OR=3.227, P<0.001) and diabetes (OR=2.795, P<0.001). Although certain factors were clearly associated with these phenomena much still remains to be learnt. [ABSTRACT FROM AUTHOR]

Randomized trials have shown significant blood pressure (BP) reductions after increased protein compared with carbohydrate intake, but the effect on BP maintenance after initial weight loss is unclear. We examined the effect of a high-protein diet on the maintenance of reduced BP after weight loss in 420 overweight adults from the Diet, Obesity and Genes study. After an 8-week weight-loss period (>8% BW), subjects (42±6 years) were randomized to either a high-protein diet (23-28 en% protein) or a lower-protein control diet (10-15 en% protein) for 26 weeks. BMI after weight loss was 30.3±4.3 kg m−2, BP was 118/73 mm Hg and 28 subjects (6.5%) used antihypertensive agents. Systolic BP during 26 weeks of weight maintenance dietary intervention increased in both treatment groups, but it was 2.2 mm Hg less (95% CI: −4.6 to 0.2 mm Hg, P=0.08) in the high-protein group than in the lower-protein control group. In 191 (pre)hypertensive subjects (baseline systolic BP⩾120 mm Hg), a larger difference was observed (−4.2 mm Hg (−7.7, −0.7), P=0.02). The effect was attenuated after adjustment for initial BP (−3.4 mm Hg (−6.9, −0.03), P=0.048), and after additional adjustment for weight change (−2.7 mm Hg (−6.1, 0.4), P=0.11). Adjustment for 24-h urinary excretion of sodium and potassium did not change the results. Diastolic BP yielded similar results. These findings suggest that a BP reduction after weight loss is better maintained when the intake of protein is increased at the expense of carbohydrates. This effect is partly mediated by body weight. [ABSTRACT FROM AUTHOR]

Peptidyl arginine deiminase (PAD)4 is a nuclear enzyme that catalyzes the posttranslational conversion of arginine residues to citrulline. Posttranslational protein citrullination has been implicated in several inflammatory autoimmune diseases, including rheumatoid arthritis, colitis, and multiple sclerosis. Here, we tested the hypothesis that PAD4 contributes to ischemic acute kidney injury (AKI) by exacerbating the inflammatory response after renal ischemia-reperfusion (I/R). Renal I/R injury in mice increased PAD4 activity as well as PAD4 expression in the mouse kidney. After 30 min of renal I/R, vehicle-treated mice developed severe AKI with large increases in plasma creatinine. In contrast, mice pretreated with PAD4 inhibitors (2-chloroamidine or streptonigrin) had significantly reduced renal I/R injury. Further supporting a critical role for PAD4 in generating ischemic AKI, mice pretreated with recombinant human PAD4 (rPAD4) protein and subjected to mild (20 min) renal I/R developed exacerbated ischemic AKI. Consistent with the hypothesis that PAD4 regulates renal tubular inflammation after I/R, mice treated with a PAD4 inhibitor had significantly reduced renal neutrophil chemotactic cytokine (macrophage inflammatory protein-2 and keratinocyte-derived cytokine) expression and had decreased neutrophil infiltration. Furthermore, mice treated with rPAD4 had significantly increased renal tubular macrophage inflammatory protein-2 and keratinocytederived cytokine expression as well as increased neutrophil infiltration and necrosis. Finally, cultured mouse kidney proximal tubules treated with rPAD4 had significantly increased proinflammatory chemokine expression compared with vehicle-treated cells. Taken together, our results suggest that PAD4 plays a critical role in renal I/R injury by increasing renal tubular inflammatory responses and neutrophil infiltration after renal I/R. [ABSTRACT FROM AUTHOR]

A novel multiscale mathematical and computational model of the pulmonary circulation is presented and used to analyse both arterial and venous pressure and flow. This work is a major advance over previous studies by Olufsen et al. (Ann Biomed Eng 28:1281-1299, ) which only considered the arterial circulation. For the first three generations of vessels within the pulmonary circulation, geometry is specified from patient-specific measurements obtained using magnetic resonance imaging (MRI). Blood flow and pressure in the larger arteries and veins are predicted using a nonlinear, cross-sectional-area-averaged system of equations for a Newtonian fluid in an elastic tube. Inflow into the main pulmonary artery is obtained from MRI measurements, while pressure entering the left atrium from the main pulmonary vein is kept constant at the normal mean value of 2 mmHg. Each terminal vessel in the network of 'large' arteries is connected to its corresponding terminal vein via a network of vessels representing the vascular bed of smaller arteries and veins. We develop and implement an algorithm to calculate the admittance of each vascular bed, using bifurcating structured trees and recursion. The structured-tree models take into account the geometry and material properties of the 'smaller' arteries and veins of radii $$\ge $$ 50 $$\upmu $$ m. We study the effects on flow and pressure associated with three classes of pulmonary hypertension expressed via stiffening of larger and smaller vessels, and vascular rarefaction. The results of simulating these pathological conditions are in agreement with clinical observations, showing that the model has potential for assisting with diagnosis and treatment for circulatory diseases within the lung. [ABSTRACT FROM AUTHOR]

The author reflects on the study conducted by G. M. Nardi et al on the important role of nitric oxide synthases (NOS1) in the pathogenesis of circulatory dysfunction in patients with sepsis. An overview on the research study on polymicrobial bacterial peritonitis in septic rats experiment is discussed. Also mentions on the development agents to ameliorate circulatory dysfunction in patients with septic shock.

BACKGROUND: The phenomenon of slow coronary flow (SCF) in the presence of normal coronary arteries may indicate endothelial dysfunction, which is characteristic of an early stage in the development of atherosclerosis. Measurement of the Carotid Intima-Media Thickness (CIMT) allows identification of early stages of atherosclerosis. CIMT might offer a non-invasive method of diagnosing SCF patients. Previous studies demonstrated conflicting results regarding the relationship between these two phenomena. In the present study, we examined the association between coronary flow velocity and the degree of CIMT in patients with angiographically normal coronary arteries. METHODS: Coronary arterial blood flow velocity was measured using two methods - Corrected Thrombolysis in Myocardial Infarction (TIMI) Frame Count (CTFC) and Coronary Clearance Frame Count (CCFC). In addition, we measured the level of the CIMT using a special automated computerized software. RESULTS: Seventy Five consecutive patients were prospectively recruited. No correlation was found between CIMT and mean CTFC (r = -0.08, p = NS) or mean CCFC (r = -0.07, p = NS). In addition, CIMT values did not differ between the SCF and the Normal coronary flow (NCF) groups (0.796 mm vs. 0.805 mm, respectively, p = 0.733). Patients with SCF had higher levels of hematocrit (39.9% vs. 36.1%, p < 0.001), LDL cholesterol (101.1 mg/dl vs. 85.8 mg/dl, p = 0.01) and higher rate of current smokers (28.9% vs. 10.8%, p = 0.05). CONCLUSIONS: Patients with angiographically normal coronary arteries and SCF do not have increased CIMT values. However, current smoking, higher LDL cholesterol and hematocrit levels are all related to slower coronary blood flow. [ABSTRACT FROM AUTHOR]

Fixed-dose combination of telmisartan and hydrochlorothiazide is another contemporary option of effective treatment of hypertension. It is a combination of an angiotensin II receptor blocker, telmisartan and thiazide diuretic, hydrochlorothiazide. Telmisartan reduces cardiovascular risk not only by reducing blood pressure (BP), but also by reducing other metabolic parameters that have a positive effect on cardiovascular diseases, especially selective modulation of PPAR-γ. Hydrochlorothiazide has an effect on the renal tubular mechanisms of electrolyte reabsorption, directly increasing excretion of sodium and chloride in approximately equal amounts. Different combinations of telmisartan and hydrochlorothiazide (40/12,5; 80/12,5 and 80/25 mg) are used in the treatment of hypertension in adults whose BP is not well controlled by using telmisartan alone or in patients who have been previously stabilized by telmisartan and hydrochlo-rothiazide administered separately. [ABSTRACT FROM AUTHOR]

Background: During acellular replacement of an acute blood loss, hyperoxic ventilation (HV) increases the amount of O2 physically dissolved in the plasma and thereby improves O2 supply to the tissues. While this effect could be demonstrated for HV with inspiratory O2 fraction (FiO2) 0.6, it was unclear whether HV with pure oxygen (FiO2 1.0) would have an additional effect on the physiological limit of acute normovolemic anemia. Methods: Seven anesthetized domestic pigs were ventilated with FiO2 1.0 and subjected to an isovolemic hemodilution protocol. Blood was drawn and replaced by a 6% hydroxyethyl starch (HES) solution (130/0.4) until a sudden decrease of total body O2 consumption (VO2) indicated the onset of O2 supply dependency (primary endpoint). The corresponding hemoglobin (Hb) concentration was defined as 'critical Hb' (Hbcrit). Secondary endpoints were parameters of myocardial function, central hemodynamics, O2 transport and tissue oxygenation. Results: HV with FiO2 1.0 enabled a large blood-for-HES exchange (156 ± 28% of the circulating blood volume) until Hbcrit was met at 1.3 ± 0.3 g/dl. After termination of the hemodilution protocol, the contribution of O2 physically dissolved in the plasma to O2 delivery and VO2 had significantly increased from 11.7 ± 2 to 44.2 ± 9.7% and from 29.1 ± 4.2 to 66.2 ± 11.7%, respectively. However, at Hbcrit, cardiovascular performance was found to have severely deteriorated. Conclusion: HV with FiO2 1.0 maintains O2 supply to tissues during extensive blood-for-HES exchange. In acute situations, where profound anemia must be tolerated (e.g. bridging an acute blood loss until red blood cells become available for transfusion), O2 physically dissolved in the plasma becomes an essential source of oxygen. However, compromised cardiovascular performance might require additional treatment. © 2013 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Systemic hypertension is characterized by high and sustained levels of blood pressure, frequently associated with functional and / or structural changes of target organs and increased risk of cardiovascular events. In Brazil there was an increase in the number of cases and prevalence, and estimated that about a quarter of Brazil's population suffers from hypertension. The diagnosis is made according to the guidelines of the VI Brazilian Guidelines for Hypertension. The indications for treatment are well established, yet still professional difficulties encountram to address and control the evolution of the disease and the onset of complications. The treatment is based on two main axes: the change in lifestyle and pharmacological treatment. One of the key aspects in successful treatment and control of hypertension is patient adherence to both drug treatment, such as non-medication. [ABSTRACT FROM AUTHOR]

The article offers information on the pathogenesis, diagnosis, management, mitigation and prevention of transfusion associated circulatory overload (TACO). It discusses the symptoms of TACO, which is diagnosed with the help of chest radiographs and invasive cardiovascular monitoring devices. It discusses risk factors, assessment of TACO in blood banks and the use of diuretic medications in treatment.

The article discusses renal sympathetic denervation (RSDN) therapy as treatment for hypertension. Topics discussed include the rationale for RSDN therapy, systemic effects of sympathetic nervous system hyperactivity and the use of RSDN therapy in clinical practice in Europe and Australia. Also mentioned is the utilization of sympathectomy before modern pharmacotherapy.

Background: Thoracic cerebrospinal fluid (CSF) hygroma is a rare and potentially devastating complication of the anterior thoracic approach to the spine. We present two cases in which this complication resulted in acute cranial nerve palsy and discuss the pathoanatomy and management options in this scenario. Case reports: Two male patients presented to our department with neurological deterioration due to a giant herniated thoracic disc. The extruded disc fragment was noted pre-operatively to be calcified in both patients. A durotomy was performed at primary disc prolapse resection in the first patient, whereas an incidental durotomy during the procedure caused complication in the second patient. These were repaired primarily or sealed with Tachosil. Both patients re-presented with acute diplopia. Imaging of both patients confirmed a massive thoracic cerebrospinal fluid hygroma and evidence of intracranial changes in keeping with intracranial hypotension, but no obvious brain stem shift. The hemithorax was re-explored and the dural repair was revised. The first patient made a full recovery within 3 months. The second patient was managed conservatively and took 5 months for improvement in his ophthalmic symptoms. Conclusions: The risk of CSF leakage post-dural repair into the thoracic cavity is raised due to local factors related to the chest cavity. Dural repairs can fail in the presence of an acute increase in CSF pressure, for example whilst sneezing. Intracranial hypotension can result in subsequent hygroma and possibly haematoma formation. The resultant cranial nerve palsy may be managed expectantly except in the setting of symptomatic subdural haematoma or compressive pneumocephaly. [ABSTRACT FROM AUTHOR]

Several retrospective studies have described the clinical manifestation of peripheral artery occlusive disease (PAOD) in patients receiving nilotinib. We thus prospectively screened for PAOD in patients with chronic phase chronic myeloid leukemia (CP CML) being treated with tyrosine kinase inhibitors (TKI), including imatinib and nilotinib. One hundred and fifty-nine consecutive patients were evaluated for clinical and biochemical risk factors for cardiovascular disease. Non-invasive assessment for PAOD included determination of the ankle-brachial index (ABI) and duplex ultrasonography. A second cohort consisted of patients with clinically manifest PAOD recruited from additional collaborating centers. Pathological ABI were significantly more frequent in patients on first-line nilotinib (7 of 27; 26%) and in patients on second-line nilotinib (10 of 28; 35.7%) as compared with patients on first-line imatinib (3 of 48; 6.3%). Clinically manifest PAOD was identified in five patients, all with current or previous nilotinib exposure only. Relative risk for PAOD determined by a pathological ABI in first-line nilotinib-treated patients as compared with first-line imatinib-treated patients was 10.3. PAOD is more frequently observed in patients receiving nilotinib as compared with imatinib. Owing to the severe nature of clinically manifest PAOD, longitudinal non-invasive monitoring and careful assessment of risk factors is warranted. [ABSTRACT FROM AUTHOR]

Purpose: Olprinone is a phosphodiesterase type III inhibitor that is often used to increase cardiac output after cardiopulmonary bypass (CPB). Hemodilution by CPB is likely to decrease total olprinone concentration, but it may also increase the free (unbound) concentration of olprinone due to reduced protein binding. The aim of this study was to investigate the effect of hemodilution on the protein binding of olprinone. Methods: Eleven patients scheduled for elective cardiac surgery with CPB were enrolled in our study. Olprinone was continuously infused at a rate of 0.2 μg/kg/min from the time of the first surgical incision until the patient arrived at the recovery unit. Protein binding was evaluated twice, just before the start of CPB and at the beginning of withdrawal from CPB. Olprinone concentration and protein binding were determined with high-performance liquid chromatography and ultrafiltration methods, respectively. Olprinone protein binding was also evaluated in vitro. Results: Olprinone protein binding to albumin was 63 % in vitro, but it did not bind to alpha-1 acid glycoprotein. Olprinone protein binding in patients before CPB was 81.5 ± 4.3 %, whereas protein binding at withdrawal from CPB was 63.3 ± 14.3 %. Conclusions: Unbound olprinone concentration increased by 20 % during CPB, which suggests that the pharmacological effects of olprinone might be enhanced during and after CPB. Close hemodynamic monitoring is necessary to control the effects of olprinone after CPB, because CPB alters olprinone's pharmacokinetics. [ABSTRACT FROM AUTHOR]

There are limited, reliable data on the prevalence of hypertension in East African populations. The aim of this study was to document the prevalence of hypertension in the rural Hai district of Tanzania. All consenting individuals aged 70 years and over who were living in 12 randomly-selected villages in the district underwent three consecutive sitting blood pressure (BP) measurements. An average of the last two measurements was taken. Prior diagnosis of, and treatment for, hypertension was recorded. Of the 2223 subjects, 1553 (69.9%, 95% CI 68.0-71.8) had hypertension (BP 140/90). Of those with hypertension 733 (47.2%) had isolated systolic hypertension. Only 586 (37.7%) hypertensives had been previously diagnosed, 94 (6.1%) were currently treated and 14 (0.9%) were adequately controlled. This is the first large-scale prevalence study of hypertension in the elderly in sub-Saharan Africa (SSA). Our results approximate to a 'rule of sixths'; 2/6 of hypertensives were previously detected, 1/6 of those previously detected were on treatment and 1/6 of those on treatment were adequately controlled. Hypertension is a large problem in the elderly population in SSA, and there are a growing number of elderly who are at risk of hypertensive sequelae owing to lack of detection and treatment. [ABSTRACT FROM AUTHOR]

Background. To investigate the effects of a single dose of metformin (MF) on endothelium-dependent vasodilatation and serum antioxidant and free fatty acid levels in patients with primary hypertension (PH) after an acute glucose load. Materials and methods. Patients with untreated PH were randomized to a no-metformin group (PH, n = 34) and a metformin group (PH+ MF, n = 28) who received a single dose of 500 mg metformin before testing. Healthy volunteers ( n = 31) served as a control group. Brachial artery endothelium-dependent flow-mediated vasodilatation (FMD) was determined at 0, 1, 2 and 3 h after glucose load. Levels of serum superoxide dismutase (SOD), total antioxidant capacity (T-AOC), anti-superoxide anion free radical (AntiO2) and free fatty acids (FFA) were measured. Results. The FMD in the PH group decreased significantly 1 h after glucose load (PH: 10.9 ± 2.9% vs 13.67 ± 3.42% before glucose load). Metformin inhibited the effects of glucose load on FMD. At 1 h after acute glucose load, the concentrations of SOD, T-AOC and AntiO2 in the PH group decreased significantly compared with their fasting levels, and metformin inhibited the acute glucose load-induced decline in SOD and T-AOC levels. Conclusions. Metformin can prevent transient endothelial dysfunction caused by acute glucose load in patients with PH. [ABSTRACT FROM AUTHOR]

A reprint of the article "Endovascular Treatment for Acute Ischemic Stroke: Still Unproven" that was published on February 8, 2013 at NEJM.org is presented. It comments on the development of intravenous lytic agents and endovascular devices to treat patients with acute ischemic stroke. It argues that a decision by Medicare to place a moratorium on reimbursement for endovascular treatment of acute ischemic stroke outside of randomized trials would facilitate recruitment in these trials.

Ozone therapy or Ozonated Autohemotherapy (O3-AHT) has been meticulously used for more than a century to improve cellular function and for quicker healing of diseased tissues. It involves administration of ozone as gas or in liquid form to kill the microorganisms. Furthermore, body provides more energy using oxygen and can eliminate wastes efficiently. Ozone is used by different health organizations for its disinfectant, antiseptic, quick healing properties, circulatory disorders, geriatric conditions, cancer, skin healing, AIDS, rheumatism/arthritis and in water treatment plants etc. It was found to be consistent safe, with minimal and preventable side effects. It should be introduced into the body in large quantities so that the singlet oxygen molecule which is unattached and freely circulating will attack all immature, sick and deformed foreign cells. Availability of ozone in gaseous state further limits its use; hence some special techniques should be designed through strong R&D input which can make this technique widely accepted. Initially ozone was believed to have treacherous effects, yet researchers alleged that it may have therapeutic benefits which directed researchers to study and synchronize its use with the current medical practices. [ABSTRACT FROM AUTHOR]

Hypertension is a major independent risk factor for cardiovascular diseases. Management of hypertension is generally based on office blood pressure since it is easy to determine. Since casual blood pressure readings in the office are influenced by various factors, they do not represent basal blood pressure. Dipping of the blood pressure in the night is a normal physiological change that can be blunted by cardiovascular risk factors and the severity of hypertension. Nondipping pattern is associated with disease severity, left ventricular hypertrophy, increased proteinuria, secondary forms of hypertension, increased insulin resistance, and increased ibrinogen level. Long-term observational studies have documented increased cardiovascular events in patients with nondipping patterns. Nocturnal dipping can be improved by administering the antihypertensive medications in the night. Long-term clinical trials have shown that cardiovascular events can be reduced by achieving better dipping patterns by administering medications during the night. Identifying the dipping pattern is useful for decisions to investigate for secondary causes, initiating treatment, necessity of chronotherapy, withdrawal or reduction of unnecessary medications, and monitoring after treatment initiation. Use of this concept at the primary care level has been limited because 24-hour ambulatory blood pressure monitoring has been the only method for documenting dipping/nondipping status so far. This monitoring technique is expensive and inconvenient for routine usage. Simpler methods using home blood pressure monitoring systems are evolving to document basal blood pressure in the night, which would help in greater acceptance and use of the concept of dipper/nondipper in managing hypertension at the primary care level. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study is to compare the effects of deksmededetomidin and remifentanyl which are used to induce controlled hypotension, on peroperative haemodynamic chages, awakening, and recovery time and Aldrete sedation score in tympanoplasty- tympanomastoidectomy surgery. Methods: This randomized double blind study was conducted with 50 ASA I-II patients scheduled for tympanoplasty-tympanomastoidectomy surgery. The patients were randomly allocated to one of 2 groups: Group R and Group D. Group R received remifentanil HCL at the rate of 0.2 mg kg-1 min-1 and Group D received deksmedetomidin at the loading dose of 1 mg kg-1 within 10 minutes. The first haemodynamic parameters of the patients were recorded as basal values, after bolus infusion and intubation and during the perioperative period were recorded every fifteen minutes. At the end of surgery, before and after extubation, and also until 60th minute after extubation, parameters were recorded every 5 minutes. The number of minutes elapsed before patients had spontaneous inspiration after infusion was stopped, opened their eyes, were extubated and were able to obey commands were all recorded. Aldrete sedation score was evaluated at the postoperative 30th minute. Results: There were no differences between the two groups with respect to basal values and post-extubation heart rate and mean arterial pressure values, beginning of spontaneous inspiration, eye opening, obeying commands, extubation time and Aldrete Sedation Score levels. Conclusion: We concluded that there was no superiority of deksmedetomidine or remifentanilin to each other in inducing controlled hypotension and also, they can be safely used for this purpose. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The study of small-molecule metabolites may assist in cardiovascular risk monitoring during therapy. We assessed whether acute changes in the metabolome by lipoprotein apheresis are able to predict changes in microvascular function. Methods: We performed mass-spectrometry-based profiling of 186 metabolites in peripheral plasma of 21 hyperlipidemic patients before and after a single session of lipoprotein apheresis. To evaluate the capability of metabolites to predict microvascular outcome after apheresis, patients were stratified according to improvement and deterioration of retinal endothelial function. Endothelial function was assessed as the relative change in retinal vessel diameter in response to flicker light stimulation. Results: We observed pronounced but not uniform changes in the metabolome after a single session of lipoprotein apheresis. Improvements in microvascular function were associated with a decline in lysophosphatidylcholines C14:0, C16:0, C16:1, C18:0, C18:1, C18:2, C20:4, C28:0, C28:1; in the amino acid serine and the dicarboxyacylcarnitine C12-DC. A positive relationship was found for methionine and ornithine. Applying decision tree and receiver–operator characteristic curve analysis, a change in serine of smaller than 11% by lipoprotein apheresis predicted an improvement of microvascular function with high sensitivity. Conclusion: Lipoprotein apheresis elicits changes in the metabolome favoring an anti-atherosclerotic environment. Monitoring the serine profile may assist in risk management of patients undergoing regular lipoprotein apheresis. [Copyright &y& Elsevier]

The article presents a study that investigates the efficacy of iptakalim in ameliorating monocrotaline arterial pulmonary hypertension of rats in the U.S. Researchers injected single dose of monocrataline (MCT) on rats and iptakalim for 28 days. They discovered that iptakalim hinders induction of MCT pulmonary arterial hypertension (PAH).

Considering high prevalence and the need to look for alternative medicine, essential hypertension was screened in light of Vata--Pitta Pradhana Rakta Pradoshaja Vikara as mentioned by Acharya Charaka. Comparing the etiological factors, symptomatology, and complications with Rakta Pradoshaja Vikara with that of essential hypertension, a striking similarity was revealed. To prove the practical approach of management of Vata--Pitta Pradhana Rakta Pradoshaja Vikara, a randomized open clinical trial on 33 uncomplicated subjects of essential hypertension was conducted. The subjects were allotted in two groups, viz. (Group A) Virechana group having 16 cases who underwent Virechana Karma by Trivrita, Aragvadha, Eranda Taila, and Draksha Kwatha as Sahapana; and (Group B) Basti group consisting of 17 cases who were administered Dashmoola Kala Basti in which Niruha with Dashmoola Kwatha and Anuvasana with Dashmoola Taila was done. Patients of both the groups were followed by Shamana Chikitsa (Arjunadi Ghanavati). The overall effect of the therapies on systolic and diastolic blood pressure showed that Virechana proved better relief (43.75%) as compared to Basti (29.41%). The response was encouraging and has created scope for further studies. [ABSTRACT FROM AUTHOR]