Effects of a Custom-Made Pillow on Sleep and Blood Pressure Circadian Rhythm

Our contemporary 24-hour (h) society influences circadian rhythms and impairs the quality of life, resulting in tiredness, emotional instability, poor judgment, etc. These adverse effects are important factors related to sleep andpsychiatric disorders. Moreover, short sleep duration and bad sleep quality are closely associated with life stylerelated diseases. Various products for obtaining good-quality sleep have been developed with the increasing recognition of the importance of getting comfortable sleep.

Sleep problems and the blood pressure (BP) circadian rhythm are closely related. A short duration of sleep is linked to a higher 24-h BP and nighttime BP in the younger generation. Increased nighttime activity has been found to influence the daytime BP rhythm, causing a smaller reduction in nighttime BP. Moreover, disturbance of the BP circadian rhythm is a risk factor for cardiovascular diseases such as cerebral infarction and hemorrhage. Poor sleep quality, defined as Pittsburgh sleep quality index (PSQI) ≥ 6, was significantly associated with resistance to treatment in hypertensive women, independent of cardiovascular and psychiatric confounders. Read more....................

Dual Blocking of the Renin Angiotensin System

The renin angiotensin system (RAS) plays an all-encompassing role in cardiovascular regulation. Indeed, the early notion defining its function as vasoconstrictive was expanded to a much broader physiological spectrum, including sodium regulation and structural cardiovascular changes. Moreover, many studies have shown the synthesis and release of various components of the RAS in a number of organs.Further research revealed disparate RAS effects on vascular tone and sodiumexcretion. That is, RAS can induce vasoconstriction or vasodilatation, natriuresis or sodium retention, hypertrophy or decreased proliferation, all depending on a diversity of angiotensin peptides that can bind to different receptors. The complexity of this system explains the multiplicity of its effects.

Predictably, inhibition of RAS at various levels potentially could yield multiple benefits. Indeed, treatments with either angiotensin converting enzyme inhibitors (ACEi), or angiotensin II receptor blockers (ARB’s) have shown important beneficial effects, many of which are independent from hypertension control. Actually, RAS inhibition is effective not only in treating essential hypertension, but also in renovascular hypertension, heart failure, diabetic nephropathy, various kidney diseases, (particularly when associated to heavy proteinuria), atherosclerosis, acute coronary syndrome, vasculitis, ventricular hypertrophy, atrial fibrillation, insulin resistance, multiple sclerosis and others. Progression in most of these conditions is linked to RAS pathobiological effects. Read more......................

Thoracic Aortic Aneurysm

An arterial aneurysm is a localized pathological dilation of the artery with a diameter of 1.5 times that of the normal artery . The histopathology of some aortic aneurysms includes medial degeneration with elastic fiber loss from the medial layer, loss of vascular smooth muscle cells, and proteoglycan deposition. Dissection of the thoracic aorta involves disruption of the medial layer with intramural hemorrhage causing propagation and tracking of blood within the media.

The DeBakey classification system states that a type I dissection originates in the ascending aorta and propagates distally to the aortic arch and typically to the descending aorta with surgery usually recommended. Type II dissection originates in and is confined to the ascending aorta with surgery usually recommended. Type III dissection originates in the descending thoracic aorta and propagates most often distally with nonsurgical treatment usually recommended. The Stanford classification system is divided into type A dissections which involve the ascending aorta and type B dissections which do not involve the ascending aorta. Surgery is usually recommended for all dissections involving the ascending aorta. Surgery is usually not recommended for dissections that do not involve the ascending aorta.  Read more.............

Glycosaminoglycans (GAGs) in Cardiovascular Disease: Searching for the Sweet Spot

One of the seminal discoveries in biology was the discovery of the structure of deoxyribonucleic acid, DNA, by James Watson, Francis Crick and Rosalind Franklin that led to the later deciphering of the genetic code by a series of exceptional researchers. Without Rosalind Franklin’s X ray crystallography work on the hydrated form of DNA, Watson and Crick would not have been able to decipher the double helix. It is this underlying structure that allows DNA to direct the transcription of RNA and later translation of the genetic code into proteins. In simple terms without understanding the structure, the geneticfunction of DNA was not evident. 

While the genetic code directs all protein synthesis, it is also true that in many instances understanding what genes are expressed and translated does not inform the actual final functions, the end result of protein expression and activity.The mere presence of a protein or enzyme also does not translate directly into an outcome in activity. Function is a much more complex process. Thus the genetic code can direct amino acid sequence and structure, but structure and location can also modify ultimate function. With this editorial we discuss the effects of one structural component, the glycosaminoglycans (GAGs), on the functional activities of other molecules, cells and organs. GAGs represent one of the silent engineers of cellular and tissue structures.  Read more.................

Coexistent Membranous Nephropathy with Doubly ANCA-Associated Crescentic Glomerulonephritis

Membranous nephropathy (MN) is the most common cause of primary nephrotic syndrome in nondiabetic, Caucasian adults, accounting for more than one third of cases. Most of patients with MN have preserved renal function at the time of presentation. Renal failure usually develops gradually in patients with MN and only rarely is complicated by acute kidney injury.

Pauci-immune necrotizing and crescentic glomerulonephritis (PNCGN) typically present with rapidly progressive glomerulonephritis (RPGN). Coexistent MN and PNCGN is a rare occurrence. We report a case of both MPO- and PR3-ANCA associated NCGN with membranous nephropathy that presented as rapidly progressiveglomerulonephritis.

Case Presentation: 

A 46-year-old Caucasian woman presented to emergency department with nausea, vomiting and weight loss. Medical history was remarkable for gastroesophageal reflux disease (GERD), fibromyalgia and depression. She noticed poor appetite and 40-pound weight loss over 2 months. Patient denied any recent history of upper respiratory tract infection, or skin infection. She was taking 4,800 mg of ibuprofen per day and no other medications. Read more.....................

Drugs and Orthostatic Hypotension

Orthostatic hypotension is defined as the reduction of systolic blood pressure of at least 20 mmHg or the dropping of diastolic blood pressure of at least 10 mmHg within 3 minutes of standing compared to baseline values. Recent studies suggest a change in reference values to 30 mmHg in diabetic patients and hypertensive subjects with clinostatic systolic blood pressure higher than 160 mmHg, as this would more accurately estimate the probability of autonomic neuropathy in those populations. Multiple system atrophy is a neurodegenerative disorder characterised by parkinsonian features, cerebellar ataxia, and autonomic failure.

In a recent consensus, reference values for the diagnosis of orthostatic hypotension in multiple system atrophy have been upgraded to 30 mmHg in systolic blood pressure or 15 mmHg in diastolic blood pressure, within 3 minutes of standing. Orthostatic hypotension can be divided into neurogenic and non neurogenic forms. Neurogenic forms are caused by a primitive damage to autonomic nervous system. Non neurogenic forms involve organs or systems regulating metabolic homeostasis and hemodynamics of the organism; in other instances, they may also be determined by external factors, such as the use of drugs, alcohol and other substances. Read more............

How Low should the Blood Pressure be reduced in Patients with Hypertension and High Risk for Coronary Artery Disease?

The more aggressive control of blood pressure among patients at high risk for coronary artery disease such as those with coronary artery disease, a 10-year Framingham risk score ≥10%, diabetes mellitus, chronic kidney disease, or other coronary artery risk equivalent with maintenance of the blood pressure below 130/80 mm Hg and below 120/80 mm Hg in patients with left ventricular dysfunction recommended by the American Heart Association (AHA) Task Force scientific statement in 2007 was based upon expert medical opinion at that time, not on prospective, randomized, adequately controlled trial data.

The Pravastatin or Atorvastatin Evaluation and Infection Therapy- Thrombolysis in Myocardial Infarction (PROVE IT-TIMI) 22 trial enrolled 4,162 patients with an acutecoronary syndrome (acute myocardial infarction with or without ST-segment elevation or highrisk unstable angina pectoris).The lowest incidence of cardiovascular events occurred with a systolic blood pressure between 130 to 140 mm Hg and a diastolic blood pressure between 80 to 90 mm Hg with a nadir of 136/85 mm. Read more....................

Statins as a Primary Prevention: Which One is Most Effective? A Systematic Review and Meta-Analysis

The metabolic pathway that produces cholesterol and other isoprenoids is known as the mevalonate pathway. The rate-controlling enzyme of this pathway is 3-hydroxy-3-methyl-glutaryl-CoA reductase or HMG-CoA reductase (HMGCR). This rate-controlling step in the biosynthesis of isoprenoids and sterols can berestricted by the use of statins.

This step involves the four-electron reductive deacylation of HMGCoA to CoA and mevalonate. It is catalyzed by HMGR in a reaction that proceeds as follows:

(S) HMG CoA + 2 NADPH + 2 H+ ⇒ (R)

Mevalonate + 2 NADP+ + CoASH

Where NADP+ is the oxidized form of nicotinamide adenine dinucelotide, NADPH is the reduced form of NADP+, and CoASH is the reduced form of CoA. One specific intervention for the use of HMG-CoA reductase inhibitors or statins is the potent effect on cholesterol.  Read more...............

Pharmacokinetics and Bioavailability of Annatto δ-tocotrienol in Healthy Fed Subjects

Several studies have reported the antioxidant, anti-inflammatory, anticancer, hypocholesterolemic and neuroprotective properties of tocotrienols in different cell lines, animal models, and in humans. However, question on the bioavailability of pure tocotrienols remained unanswered. Therefore, it is important to understand the absorption and bioavailability mechanism of tocotrienols before carrying out investigations into the therapeutic efficacy in humans. The bioavailability of naturally-occurring tocotrienols differ considerably in their absorption, therfore therapeutic uses of tocotrienols remain controversial.

It was reported that after feeding rats mixed tocotrienols, the oral bioavailability of α-tocotrienol was 28% compared to 9% of γ-tocotrienol and δ-tocotrienol. Tocotrienols in humans were detected in postprandial plasma, and they were found enriched in triacylglycerol-rich particles, HDL, and LDL after administration of palm tocotrienol-rich fraction (mixture of 68% tocotrienol + 32% α-tocopherol). The key parameter of bioavailability determination, the total area under the concentration-time curve (AUC0 - ∞, h) for plasma α-tocotrienol, was 60% larger than for γ-tocotrienol.   Read more..............

Role of Uremic Compounds in Organ Injury

In health, the renal glomerular filter cleanses the body of molecules with weights up to 58 kDa. In renal failure the reduced glomerular filtration or renal metabolism and the damage to non-renal organs comprise a variety of compounds specifically related to the metabolic processes and function of different cell types and organs. Inadequate removal of a large number of potentially toxic organic metabolites from the vascular bed into the urine in the course of acute kidneyinjury (AKI) and chronic kidney disease (CKD) is associated with various clinical symptoms which are often difficult to interpret.

It is of considerable importance to identify which of the uremic retention solutes are actually uremic toxins and what pathomechanisms are involved in their damaging effect on the kidneys and other organs. This would allow better documented confirmation of the suspected association between the clinical symptoms and uremic retention solute/ toxin concentrations in biological materials, possible discovery of any missing pathophysiological links between progressive renal failure and loss of function in organs other than the kidneys, and identification of diagnosis-and organ-specific biomarkers for use in clinical practice. Uremic retention solutes are referred to as uremic toxins when they interact with normal biological functions. Read more..............

Resistant Hypertension

Hypertension (HTN) is the most common cardiovascular disease and remains a major risk factor for coronary heart disease, cerebrovascular disease, heart failure and renal failure. Fewer than half of patients with HTN in the United States reach their Blood Pressure (BP) goals despite availability of numerous inexpensive generic Antihypertensive Drugs (AHDs) . Approximately 5-10% (up to 20-30%) of patientswith inadequately-controlled HTN have resistant HTN, defined as BP that remains above goal despite optimal doses of 3 AHDs including a diuretic. Resistant HTN includes patients whose BP is controlled on ≥ 4 AHDs but excludes patients whose BP is uncontrolled on a suboptimal AHD regimen or <3 AHDs.

Recent studies suggest that the prevalence of resistant HTN may be increasing over time. Predictors of inadequately-controlled BP that characterize resistant HTN patients include older age, obesity, higher systolic BP, diabetes, Left Ventricular Hypertrophy (LVH), and Chronic Kidney Disease (CKD). Patients with resistant HTN are at elevated risk for adverse cardiovascular outcomes, particularly stroke and hospitalization for heart failure. In this review, we discuss the evaluation and medical management of resistant HTN and describe investigational device-based techniques for management of resistant HTN. Read more...................

Attenuation of Hindlimb Ischemia after Associated Autologous Transplantation of Bone Marrow Mononuclear Cells and Platelet Rich Plasma

Obstructive peripheral arterial occlusive disease (PAOD) of the inferior members is a worldwide health problem and its prevalence is estimated in 27 million of people in Europe and North America. PAOD development is a multifactorial process with a variety of severe manifestations as ischemic rest pain, ulcerations, and gangrene increasing the risk of claudication, poor wound healing, limb amputation, and stroke. The therapy for PAOD has increased in thelast decades with the introduction of regenerative therapy.

The use of stem-cells, vascular endothelial growth factor (VEGF), and fibroblast growth factor FGF significantly improved symptoms and hemodynamics variables in the treated limbs, as reported in the literature. Bone marrow mononuclear cells (BMCs) or platelet rich plasma (PRP) therapies are delivered locally into affected tissues and can contribute to the regeneration of ischemic tissues and enhance the neovascularization of ischemic hindlimbs through both, cellular and paracrine mechanisms. Read more...................

Combination Therapy with Olmesartan/Hydrochlorothiazide to Improve Blood Pressure Control

High blood pressure (BP) is a major risk factor for cardiovascular disease, contributing to the premature death of millions of patients worldwide each year. In the most recent 2013 Guidelines of the European Society of Hypertension (ESH)/European Society of Cardiology (ESC) for the management of arterial hypertension, high blood pressure is defined, based on results of randomized controlled trials (RCTs), as a systolic blood pressure (SBP) ≥ 140 mmHg and/or a diastolic blood pressure (DBP) ≥ 90 mmHg. According to recent epidemiological surveys, the overall prevalence of hypertension in the general population ranges from 30 to 45%, and increases markedly with age.

Increased mean BP values correlate with the development of cardiovascular disease (CVD) morbidity/mortality in a linear relationship; consequently, the greater the reduction in blood pressure, the greater the reduction in the risk. ESC/ESH Guidelines point out that the initial choice of antihypertensive medication should be based on the magnitude of BP elevation, as well as on the concomitant level of total cardiovascular (CV) risk. Read more..............

Is percutaneous coronary intervention really effective for cardiac arrest?

Cardiac arrest accounts for more than 11% of total deaths in the world. Recently a survey was conducted to find out the success rate of percutaneous coronary intervention (PCI) in cardiac arrest patients. This survey showcased that PCI has improved survival rate ofpatients with cardiac arrest irrespective of cause of the stroke.

Nationwide inpatient sample database (NIS) from 2008-2012 was used to select the study cohort. NIS is a subset of the “Healthcare Cost and Utilization Project” (HCUP) sponsored by the agency for healthcare research and quality. The NIS is the largest publicly available all-payer inpatient care database in the United states (US), including data on approximately 7 to 8 million discharges per year, and is a stratified sample designed to approximate a 20% sample of US community (nonfederal, short-term, general, and specialty) hospitals . National estimates are produced using sampling weights provided by the sponsor.  Read more..............................

Nutritional Epidemiological Tools for Sodium Intake

Cardio metabolic diseases (metabolic syndrome and diabetes mellitus 2), are associated to cardiovascular risk factors such as dyslipidemia, abdominal obesity, insulin resistance, and high blood pressure or hypertension, which increase the risk of cardiovascular diseases (CVD), with high global prevalence.

Hypertension as a risk factor of CVD results from an interaction between genetic susceptibility and environmental factors. Diet, and specifically dietary sodium, is a determinant of blood pressure. The relation between salt and blood pressure has been studied for many decades. Dietary intake of sodium, or salt, is strongly associated with blood pressure due its central role in determining blood volume. Modern diets provide excessive amounts of salt, and in developed and developing countries the intake of processed foods with high salt levels is increasing.  Read more...............

C4d Glomerular Deposits and Disease Progression in Native Idiopathic Membranous Nephropathy

Increasing evidence from animal studies support the hypothesis that progression of renal failure in glomerular diseases is related by local complement activation. Interstitial vascular C4d vascular deposits have been described in acute and chronic antibody-mediated rejection (ABMR) . C4d is a surface-bound split product of inactive C4b obtained from classical or lectin complement pathways. To the date, receptor for C4d has not been identified and its biological function is unknown. C4d positive staining (C4d+) has also been reported in normal human kidneys, primary  and secondary nephropathies. 

The weak segmental C4d+ glomerular staining observed in normal kidney biopsies possibly results by local complement activation involved in the physiological clearance of IgM-containing immune complexes . A study on C4-deficient guinea-pig showed increased IgM glomerular deposits when compared to non C4ddeficient mammalian kidneys. Human diseases studies suggest that C4d+ mesangial staining in patients with IgA nephropathy (IgAN) could identify individuals with a worse long-term prognosis. Read more........................

Integrative Approach of Venous Return And Cardiac Output in the Context of Skeletal Muscle Atrophy

The main function of the cardiovascular system is to supply cells with nutrients and oxygen and to remove excretes from their metabolism. This function, along with the general constitution of the cardiovascular system, has been known since Harvey's findings in the 17th century. He demonstrated that the heart was the central organ of the cardiovascular system, and that it was responsible for propelling the blood to the arteries and veins and back to its starting point. This unidirectional blood flow was ensured by Harvey's description of valves in the venous system, which allows blood to flow toward the heart preventing itfrom going in the opposite direction.

In the 19th century, Bayliss and Starling broadly described function and control of the venous system. Afterward, in the 1950's, Guyton et al. further explored the venous system control and its relationship with right atrial pressure. Nevertheless, during the years, the venous side physiology has not been as appreciated as the arterial side; hence it being left out of the circulatory system physiology. Currently, the two basic known functions of the venous system are to return the blood from the periphery to the right atrium and to store large amounts of unneeded blood serving as a reservoir. Read more...............

FGF10 Signaling Enhances Epicardial Cell Expansion during Neonatal Mouse Heart Repair

In contrast to newt and zebrafish, adult mammalian hearts have a very limited capacity to regenerate. Ischemia in the mammalian heart causes significant tissue damage with the loss of many cardiac cells through apoptosis and necrosis, only to be replaced with nonfunctional fibrotic tissue and hypertrophy but not hyperplasia of the remaining cardiomyocytes. After an ischemic episode, the heart is permanently scarred and functionally impaired, leading to lifelong morbidity or ultimately death. 

Cardiovascular disease affects millions of people in the USA and is the leading cause of all mortality. Determining the precise mechanisms and initiators for regeneration may lead to possible therapeutic agents for human patients, decreasing mortality and morbidity from ischemic heart diseases. Recently, neonatal mouse hearts were shown to regenerate after ventricular resection in a similar fashion to adult zebrafish. Furthermore, it was demonstrated they can also regenerate after ischemia created by coronary artery ligation. Read more..............

Treatment of Severe Aortic Stenosis

Severe valvular aortic stenosis (AS) is an aortic valve area of less than 1.0 cm2. Angina pectoris, syncope or near syncope, and congestive heart failure (CHF) are the 3 classic manifestations of severe AS. Patients with symptomatic severe valvular AS have a poor prognosis. Ross and Braunwald found that the average survival rate was 3 years after the onset of angina pectoris in patients with severe AS. Ross and Braunwald reported that the average survival rate after the onset of syncope in patients with severe AS was 3 years. 

Ross and Braunwald showed that the average survival rate after the onset of CHF in patients with severe AS was 1.5 to 2 years. In a prospective study, at 19-month follow-up (range 2 to 36 months), 90% of 30 patients with CHF associated with unoperated severe AS and a normal left ventricular ejection fraction (LVEF) were dead. At 13-month follow-up (range 2 to 24 months), 100% of 18 patients with CHF associated with unoperated severe AS and an abnormal LVEF were dead. Read more..............