Farr A Curlin, MD

• Professor of Medicine
• Professor of Medical Humanities

https://medicine.duke.edu/faculty/farr-curlin-md

There are significant levels of ascorbic acid in the seminal plasma cholesterol lowering foods eggs lipitor 10 mg order line, as there is twice as much compared to uric acid and three times as much compared to thiols in semen samples from fertile men [49] cholesterol levels ranges discount lipitor 20 mg on-line. While lycopene has been localized in the prostate [34] cholesterol test results mmol/l cheap lipitor on line, it may not be secreted as analysis of seminal plasma did not detect its presence [49] cholesterol enhancing foods cheap 40 mg lipitor free shipping. Within the cellular environment cholesterol levels and stroke risk quality lipitor 10 mg, reductive stress from glutathione may trigger mitochondrial oxidation and cytotoxicity [50]. At greater oxidative potentials, there was an Causes of Reductive Stress in Male Reproduction Chapter 1. The emerging clinical impact of reductive stress has been demonstrated by animal studies of the cardiovascular system [53,54]. Heat-shock protein 27 was used as a cardiac-specific antioxidant expressed at varying levels in transgenic mice. This reduced state recapitulated the development of cardiomyopathy as these mice demonstrated decreased cardiac function and an overall lower survival rate [53]. The potential impact of reductive stress has also been demonstrated in studies of the nervous system [55e57]. High concentrations of antioxidants have not conferred protection to the nervous system and may even be detrimental to neurons [55]. In an animal study, endothelial cells from mouse brains were incubated and exposed to various concentrations of antioxidants sourced from fermented rooibos tea. Furthermore, there was also decreased permeability across the bloodebrain barrier associated with antioxidant exposure [56]. Fisher and Mentor attributed these changes to reductive stress from excess antioxidant exposure [57]. They suggested that reductive stress could limit the ability of the brain microenvironment to repair capillaries and respond to injury through suppression of cellular proliferation, membrane transport, and mitochondrial function [57]. Within the setting of the male reproductive system, antioxidant supplementation may impact physiologic reactions through the loss of oxidative mechanisms. As previously discussed, cellular functions, such as protein folding and disulfide bridge formation, can be altered with ascorbic acid supplementation [8]. Seminal concentrations of ascorbic acid respond to dietary depletion or repletion of this reducing agent [58]. However, dietary ascorbic acid depletion in the semen may not necessarily impact spermatic function in healthy fertile men [58]. Furthermore, high-dose supplementation with 1000 mg of daily ascorbic acid and 800 mg of daily tocopherol does not improve semen parameters or sperm survival in patients with asthenozoospermia or reduced sperm concentration [59]. Ascorbic acid may actually act as a prooxidant that can promote cellular damage [60e62]. The role of ascorbic acid as an antioxidant or a prooxidant may be influenced by its dosing. Male subjects supplemented with various doses of ascorbic acid ranging from 50 to 4000 mmol underwent semen analysis for sperm motility, sperm viability, and lipid peroxidation. Dosing below 1000 mmol resulted in a dose-dependent improvement in motility and viability as well as a decrease in lipid peroxidation [63]. In addition to dosing levels, the protective versus damaging effect of ascorbic acid may also depend on the timing of its administration within the setting of oxidative damage. In a study evaluating the role of antioxidant supplementation in oxidative stress, ascorbic acid was protective if administered before the initiation of cellular injury [62]. However, if ascorbic acid was administered after damaged cells had already released free transition metal ions, it generated a more reductive state that worsened the extent of injury [62]. Other reducing agents used for antioxidant supplementation may also act through the antioxidant paradox and cause additional harm. These studies demonstrate that antioxidant supplementation is not without its risks. In an attempt to treat oxidative stress in male infertility, antioxidants can result in an imbalance to the other extreme and can lead to paradoxical injury through reductive stress. As there is a lack of dosing guidelines or regulations for antioxidant treatment, there is potential for oversupplementation. As our understanding of oxidative and reductive reactions affecting male fertility continues to develop, more studies are needed to elucidate the phenomenon of reductive stress and its effect on male reproduction. White blood cells cause oxidative damage to the fatty acid composition of phospholipids of human spermatozoa. Yeast flavin-containing monooxygenase generates oxidizing equivalents that control protein folding in the endoplasmic reticulum. Evidence for an essential role of reactive oxygen species in the genesis of late preconditioning against myocardial stunning in conscious pigs. Formation of hydrogen peroxide by spermatozoa and its inhibitory effect of respiration. Capacitation and acrosome reactions in human spermatozoa monitored by a chlortetracycline fluorescence assay. Involvement of reactive oxygen species in human sperm acrosome reaction induced by A23187, lysophosphatidylcholine, and biological fluid ultrafiltrates. Relationship between seminal antioxidant enzymes and the phospholipid and fatty acid composition of spermatozoa. Protective role of superoxide dismutase in human sperm motility: superoxide dismutase activity and lipid peroxide in human seminal plasma and spermatozoa. Cloning of the mouse gene encoding plasma glutathione peroxidase: organization, sequence and chromosomal localization. Lycopene, an antioxidant carotenoid, attenuates testicular injury caused by ischemia/ reperfusion in rats. Tissue distribution of lycopene in ferrets and rats after lycopene supplementation. Investigation of detoxification capacity of rat testicular germ cells and Sertoli cells. Reactive oxygen species in semen of infertile patients: levels of superoxide dismutase- and catalase-like activities in seminal plasma and spermatozoa. Distribution and possible novel role of phospholipid hydroperoxide glutathione peroxidase in rat epididymal spermatozoa. A review of the physical and chemical properties of human semen and the formulation of a semen simulant. Reactive oxygen species production by the spermatozoa of patients with idiopathic infertility: relationship to seminal plasma antioxidants. Studies on the origin of redox enzymes in seminal plasma and their relationship with results of in-vitro fertilization. Comparison of individual antioxidants of sperm and seminal plasma in fertile and infertile men. Glutathione-dependent reductive stress triggers mitochondrial oxidation and cytotoxicity. Increased reactive oxygen species production during reductive stress: the roles of mitochondrial glutathione and thioredoxin reductases. Involvement of reductive stress in the cardiomyopathy in transgenic mice with cardiac-specific overexpression of heat shock protein 27. Human alpha B-crystallin mutation causes oxido-reductive stress and protein aggregation cardiomyopathy in mice. Aggressive antioxidant reductive stress impairs brain endothelial cell angiogenesis and blood brain barrier function. Antioxidant-induced reductive stress has untoward consequences on the brain microvasculature. Antioxidant treatment of patients with asthenozoospermia or moderate oligoasthenozoospermia with high-dose vitamin C and vitamin E: a randomized, placebo-controlled, double-blind study. In vivo dual effects of vitamin C on paraquat-induced lung damage: dependence on released metals from the damaged tissue. Human sperm motility and lipid peroxidation in different ascorbic acid concentrations: an in vitro analysis. They are made up of one or more electrons with unpaired valence electron(s) in the outer shell [1]. In physiological amounts, they have an active involvement in the majority of normal functions of living organisms. At minimal concentrations, it exerts a key physiological role in activating the intracellular signaling pathways involved in spermatozoa maturation and function. Male infertility affects 15 out of every 100 couples within the reproductive age group, with the male factor being the cause for half of these cases [5]. There is increasing evidence that oxidative stress is a chief causative factor that leads to male infertility [6,7]. Second, spermatozoa, being almost devoid of cytoplasm, contain very low concentrations of scavenging enzymes [9]. Thus the sperm relies heavily on the antioxidant enzymes present in the seminal plasma to help protect the plasma membrane surrounding the acrosome and tail. It is a typical by-product of oxidative phosphorylation during cellular respiration in the mitochondria. Superoxide anion reacts with itself in a dismutation reaction to produce hydrogen peroxide and oxygen molecule, O2. Superoxide anion can produce the hydroxyl radical through the metal-catalyzed Haber-Weiss reaction or the Fenton reaction, whereby ferrous ions act as reducing agents in the generation of the hydroxyl radical from hydrogen peroxide [11]. The highly reactive hydroxyl radical is responsible for the initiation of the lipid peroxidation cascade, which consequently leads to a detrimental loss of sperm function [13]. Among the factors that can activate leukocytes are infection and inflammation [17]. During the normal sperm differentiation and maturation process, excess cytoplasm is extruded into a residual body. Nitric oxide reacts with superoxide anion to form the highly toxic peroxynitrite anion [25]. The maturation process of spermatozoa involves highly organized physiological development along with morphological alterations leading up to sperm activation. During spermatogenesis, the spermatogonia undergo mitosis either to provide a renewing stem cell population or to produce primary spermatocytes. Mitosis functions to proliferate and maintain a pool of spermatogonia cells, whose genetic contents are identical to its parent cell. Throughout the entire meiotic phase, homologous chromosomes pair up, cross over, and exchange genetic material to produce an entirely new genome, ensuring genetic diversity [30]. Next spermiogenesis takes place where haploid spermatids undergo morphological changes to form highly specialized spermatozoa with remodeled and fully compacted chromatin. Human sperm go through eight different stages as it matures from spermatid to spermatozoa. Morphological changes noted include progressive condensation of the nuclear chromatin and inactivation of the genome, as well as formation of the axoneme, acrosome cap, and flagellum [31]. Toward the end of spermiogenesis, the surrounding Sertoli cells extrude and phagocytose most of the sperm cytoplasm, producing residual bodies [32]. The remnant portion of Sertoli cell cytoplasm becomes the cytoplasmic droplet present around the midpiece of the spermatozoa after spermiogenesis [20]. Along with the various steps that occur during sperm maturation, cytoplasmic extrusion is a critical step in attaining the sperm-zona binding capacity and sperm fertilization potential [34]. Following spermiogenesis, the mature but immotile spermatozoa travel from the Sertoli cell into the lumen of the seminiferous tubules. Spermatozoa then pass from the testis to the epididymis where posttesticular concentration, maturation, and temporary storage of spermatozoa take place. During the passage through the epididymis, spermatozoa attain their full maturity, ability to fertilize, and motility [35]. However, it is only in the postejaculatory phase that spermatozoa are able to move under their own control. During sperm maturation in the epididymis, sperm plasma membrane is altered based on removal, as well as addition and rearrangement of novel sperm surface proteins [36]. Not only does the spermatozoa undergo membrane, nuclear, and enzyme-related remodeling during its time in the epididymis, the signal transduction mechanism required for the subsequent capacitation and hyperactivation events are also put in place [36,37]. During the protamination of sperm chromatin, histones are initially replaced by transition proteins, and then subsequently by protamines [38]. Protamination facilitates the condensation of sperm chromatin, which helps protect the paternal genome from damage. Approximately 85% of histones are substituted with protamines during the protamination process, while the remaining 15% are carried over by the mature spermatozoa [40]. Shortly after fertilization, the protamines in the sperm chromatin are replaced by histones from the oocyte. This decondensation of the sperm nucleus then leads to the formation of a male pronucleus [41]. Protamines, which contain an abundance of cysteine residues, are phosphorylated immediately upon its synthesis. As spermatozoa move from the caput to caudal epididymis, strong disulfide bonds are formed between the cysteine residues of the protamines (by oxidation of the thiol groups of cysteine residues), which contribute to the stability of the chromatin [45]. The sperm mitochondrial capsule encases the outer membrane of the mitochondria of mammalian spermatozoa. The process of spermatogenesis requires a high amount of testosterone within the testis. Prolactin along with inhibin, which is secreted by the Sertoli cells, both take part in the regulation of normal sperm development [53]. Release of these hormones that are involved in testicular function is regulated via a feedback mechanism along the hypothalamic-pituitary-testicular axis. In one study, males with two or more past in vitro fertilization or intracytoplasmic sperm injection failures were given a daily oral antioxidant regime comprising vitamins C and E, b-carotene, zinc, and selenium for 90 days to encompass a complete spermatogenesis cycle [58].

Diseases

• Jancar syndrome
• TNF receptor associated periodic syndrome (TRAPS)
• Chromosome 1, trisomy 1q32 qter
• Hypobetalipoproteinaemia ataxia hearing loss
• Blaichman syndrome
• Lysosomal alpha-D-mannosidase deficiency
• McDonough syndrome

While the study found significant differences between groups test cholesterol gratuit quebec 10 mg lipitor order otc, a double-blind trial conducted in 2004 failed to replicate these findings and found no difference between control and riboflavin rats cholesterol check up fasting generic lipitor 5 mg online. While riboflavin has shown potential for preventing headache cholesterol on natural hair buy generic lipitor on-line, in the case of acute migraine headache cholesterol medication and high blood pressure discount lipitor 40 mg online, administration of magnesium via intravenous means can work as an abortive agent cholesterol test large small lipitor 40 mg order visa. Grown throughout the United States and Europe, Tanacetum parthenium (feverfew) is a plant that produces parthenolide, a compound believed to inhibit proinflammatory agents. This potential to prevent inflammation has resulted in studies to assess whether it can attenuate or prevent headaches, but results so far have been mixed. Another plant of interest in headache treatment is Petasites hybridus root (butterbur). In 2004 two studies were conducted looking at different doses of butterbur (one looking at daily 50 or 75 mg doses, the other using 50 mg doses twice a day) versus placebos, and both found significant reductions in headache frequency following butterbur treatment for 12 weeks for daily 75 mg and two daily 50 mg doses. Opioids-valerian root, kava, chamomile 20 To what scientific standard should complementary or alternative medicine therapies be held It is worth considering that there are many current, mainstream medical practices that have never undergone truly rigorous scientific examination: the best practices for preventing stroke other than lowering blood pressure are still being tinkered with, the use of epidural steroid injections for pain relief is still not fully accepted, and much of the work with lower back surgeries has been conducted without properly randomized trials. Just because something is currently the standard does not necessarily make it correct or the best, and what is standard in one area may be an alternative treatment in another. Practitioners should also inquire about the confidence of others who utilize the particular treatment modality. Due to the potential for a drug-herb/supplement interaction having potential deleterious consequences, it is crucial that practitioners, both mainstream and alternative, conduct thorough medication history checks in order to prevent such interactions. Acupuncture as a prophylactic treatment of migraine without aura: a comparison with flunarizine. Potential physical malpractice liability associated with complementary and integrative medical therapies. Emerging credentialing practices, malpractice liability policies, and guidelines governing complementary and alternative practices and dietary supplement recommendations. A critical review of randomized controlled trials of static magnets for pain relief. Petasites hybridus root (butterbur) is an effective preventative treatment for migraine. A combination of riboflavin, magnesium feverfew for migraine prophylaxis: a randomized controlled trial. Electromyographical ischemic test and intracellular and extracellular magnesium concentration in migraine and tension type headache patients. The effect of acupuncture on the acute withdrawal symptoms from rapid detoxification. The effectiveness of electroacupuncture in the management of chronic low back pain. Statistical reanalysis of four recent randomized trials of acupuncture for pain using analysis of covariance. Index Page numbers followed by "f" indicate figures, "t" indicate tables, and "b" indicate boxes. This was the first piece of evidence that sperm cells did have active mitochondria, or, as better phrased by MacLeod, that within the samples he was measuring there was evidence for an "active cytochrome" system. We can only presume that at that time, MacLeod also (reasonably) assumed that other cytochrome systems within the mitochondria could also be responsible. Therefore, MacLeod furthered his work by looking at the impact that high oxygen levels had on sperm cells. However, when these conditions were repeated in the presence of catalase, an enzyme that converts hydrogen peroxide into water and oxygen, cells were able to retain their motility [2]. The notion here is that when forced to use oxidative phosphorylation, a toxic by-product is created in the form of hydrogen peroxide. We can assume that MacLeod reasoned that either the sperm mitochondria made hydrogen peroxide directly, or (as we understand today) that two molecules of superoxide anion reacted with each other (dismutation) to form hydrogen peroxide, which breaks down into oxygen radicals that are consequently detrimental to sperm. However, in a repeat of the experiment, Whittington and Ford decided to investigate the contribution of leukocyte contamination with the MacLeod experiment [10]. The majority of men have leukocytes present in their semen, something MacLeod may not have known at that time. Whittington and Ford also used Percoll gradients to isolate sperm populations free of both precursor germ cells, and more importantly, leukocytes [10]. However, the enzyme is so active that spermatozoa can be immobilized by as little as 6 Â 105 stimulated leukocytes [12]. Thus in the original experiment by MacLeod it appears that leukocytes were the main contributor. Arguably, Thaddeus Mann was one of the first to realize the potential clinical significance of this association, in a landmark paper with Roy Jones and Dick Sherins published in 1979 [13]. These suspensions were then added to sperm in the presence of ascorbate and ferrous sulphate. The consequence of this would be a loss of protein function, leading to sperm immobilization [19]. Much of the earlier work involved the use of ascorbate plus ferrous ion [13,20,21], which initiates a cascade of reactions that produces superoxide anion radical, hydrogen peroxide, and hydroxyl radicals. The pathway by which this occurs is the same pathway Jones investigated earlier, where an unsaturated fatty acid becomes oxidized upon interaction with an oxygen radical, leading to aldehyde formation. Yet, while it is clear that external addition of these compounds are detrimental to sperm, what remains a challenge to the field is the in vivo significance, or spontaneous lipid peroxidation. Of particular interest is that over this same time period, a loss in total progressive motility from 43. Strikingly in the horse, both glutathione transferase and aldehyde dehydrogenase appear to play a role in detoxifying any aldehyde build up [31]. However, in both rabbit and mouse, studies have shown that this process is slow and takes place at a rate equivalent to the lifetime of the sperm cell [32]. The same has been shown to be true for human spermatozoa, even though the lifetime of a human sperm inside the female reproductive tract can be several days [18,19]. Interestingly, by putting human sperm cells in a high Naþ medium, motility within different ejaculates can be lost from 1 to 11 h [33]. This strongly suggests that peroxidation involving superoxide anion plays not just a significant role, but perhaps the major role when it comes to loss of sperm motility over time. Questions that deserve consideration in this context ask why is this the case and why are spermatozoa vulnerable in this regard Data on leukocyte numbers in semen are always hard to interpret because we have no idea when the leukocytes entered the seminal compartment, whether they were activated, when they were activated, and how they were activated. In all probability, the first time that spermatozoa see large numbers of leukocytes is at the moment of ejaculation because significant numbers of leukocytes are rarely seen in the lumina of the seminiferous or epididymal tubules. At the moment of ejaculation, spermatozoa will be protected by the antioxidants present in seminal plasma [58]. Of course, as soon as the seminal plasma is removed, the leukocytes are able to attack the spermatozoa with impunity; it is for this reason that strong associations exist between the presence of leukocytes in washed sperm preparations and fertilization rates in an in vitro fertilization setting [59]. First, the addition of the ionophore A23187 to oligozoospermic samples produced a luminol-dependent chemiluminescent signal [61]. Yet probably for all these reports, they were simply looking at the presence of cytochrome B5/P450reductases. However, a formal role in the process of either sperm maturation (capacitation) and/or male-factor infertility is yet to be documented. Unfortunately, like many of their predecessors, this same group also failed to purify the sperm cells and simply used washed ejaculates. As such, the contribution of leukocytes to their assay cannot be ruled out [10,68]. To explain this, the authors speculate that an alternate-splicing isoform was found by the antibody, yet to date, no further ratification of this idea has come forward [76]. In complex I, superoxide anion is produced on the matrix side by the oxidation of reduced flavin or flavin semiquinone [81]. A second site within the cytochrome bc1 complex of mitochondria has also been shown to produce superoxide anion, albeit this would be produced within the intermembrane space [82]. Although in his original publication, MacLeod makes note that by using traditional biochemistry he could not detect mitochondrial function in spermatozoa, this does not mean they are not active. An ideal probe would be one that is highly reactive, specific, and without other reactivity. Unfortunately, currently, no such probe exists and as such, potentially false conclusions are being drawn. Several warnings have appeared in the literature on the use of this probe for measurement of oxygen radicals. For example, "Luminol is known to elicit chemiluminescence under almost an unlimited variety of conditions" [85], or "luminoldependent chemiluminescence used in biological systems is prone to many interferences, which are difficult to control" [85], and finally, "luminol. The main area of concern is that luminol cannot react directly with superoxide anion, but must first be converted into a radical. While this luminol radical is capable of reacting with superoxide anion, it will also react with many compounds capable of donating an electron. This principle is demonstrated around the world on a daily basis when luminol-dependent immunoblotting is performed. Thus there are many compounds that the luminol-radical may interact with in a cellular environment. Therefore, trying to ascertain the contribution of superoxide anion from the other reacting compounds cannot be achieved. Despite this, many authors assume that all the fluorescence is contributed by the superoxideemediated product 2-hydroxyethidium. Using High Performance Liquid chromatography and a reversed phase column, the ethidium and 2-hydroxyethidium peaks can be separated and resolved [93]. In this manner, the contribution of superoxide anion to the overall signal can be deciphered. However, if this is the case, such oxidative stress is occurring well before the production of a sperm cell and unfortunately can be used only as an endpoint of spermatogenesis. In looking forward in this field, there are a few lessons that we need take into account. Their presence will always cast doubt as to the true interpretation of the data as clearly evidenced from the work of John MacLeod. Pharmacology of free radicals and the impact of reactive oxygen species on the testis. Human spermatozoa quantitative proteomic signature classifies normo- and asthenozoospermia. Reactive oxygen species generation and human spermatozoa: the balance of benefit and risk. The effect of incubation periods under 95% oxygen on the stimulated acrosome reaction and motility of human spermatozoa. Reactive oxygen species generated by human neutrophils inhibit sperm motility: protective effect of seminal plasma and scavengers. Comparison of methods for determining fatty acid oxidation produced by ultraviolet irradiation. Chemistry and biochemistry of 4-hydroxynonenal, malonaldehyde and related aldehydes. A-kinase anchoring protein 4 binding proteins in the fibrous sheath of the sperm flagellum. Human glyceraldehyde 3-phosphate dehydrogenase-2 gene is expressed specifically in spermatogenic cells. Defining the mechanism by which the reactive oxygen species by-product, 4-hydroxynonenal, affects human sperm cell function. The effect of reactive oxygen species on equine sperm motility, viability, acrosomal integrity, mitochondrial membrane potential, and membrane lipid peroxidation. Aldehyde dehydrogenase plays a pivotal role in the maintenance of stallion sperm motility. Spontaneous lipid peroxidation in rabbit epididymal spermatozoa: its effect on sperm motility. Spontaneous lipid peroxidation and production of hydrogen peroxide and superoxide in human spermatozoa Superoxide dismutase as major enzyme protectant against oxygen toxicity. Superoxide dismutase in human sperm suspensions: relationship with cellular composition, oxidative stress, and sperm function. Role of reactive oxygen species and antioxidants on pathophysiology of male reproduction. Depletion of intracellular thiols and increased production of 4-hydroxynonenal that occur during cryopreservation of stallion spermatozoa lead to caspase activation, loss of motility, and cell death. Sperm motility is lost in vitro as a consequence of mitochondrial free radical production and the generation of electrophilic aldehydes but can be significantly rescued by the presence of nucleophilic thiols. Sperm oxidative stress and the effect of an oral vitamin E and selenium supplement on semen quality in infertile men. Lipid peroxidation in human spermatozoa as related to midpiece abnormalities and motility. Malondialdehyde levels in sperm and seminal plasma of asthenozoospermic and its relationship with semen parameters. Docosahexaenoic acid supplementation fully restores fertility and spermatogenesis in male delta-6 desaturase-null mice. Immature germ cells in semenecorrelation with total sperm count and sperm motility. Does leukocytospermia associate with poor semen parameters and sperm functions in male infertility Seminal leucocyte subpopulations and sperm function in fertile and infertile Chinese men. Oxidative stress, spermatozoa and leukocytic infiltration: relationships forged by the opposing forces of microbial invasion and the search for perfection. Stimulation of oxidant generation by human sperm suspensions using phorbol esters and formyl peptides: relationships with motility and fertilization in vitro.

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Additionally cholesterol definition quizlet lipitor 5 mg buy line, bed rest is important to reduce metabolic needs and cardiac workload average cholesterol daily cheap lipitor 10 mg mastercard. A pericardiocentesis may be performed to withdraw excess fluid from pericardium cholesterol levels vitamin d generic lipitor 10 mg, or a pericardiectomy (a surgical procedure in which a window is created in the pericardium) may be performed to release constriction and allow excess fluid to drain into the pleural cavity cholesterol test machine lipitor 20 mg on-line. Infective Endocarditis Infective endocarditis (previously called bacterial endocarditis) is an infection of the endocardium (inner layers of the heart) or heart valves cholesterol levels test results lipitor 5 mg line. The pathogenesis of this condition involves endothelial damage, which attracts platelets and stimulates thrombus formation. With each heart contraction, some of this vegetation is dislodged and ejected from the heart. These small thrombi move throughout the body, collecting in the microcirculation and creating microhemorrhages. The thrombi can also travel to other locations, in which case they are known as embolisms, and become lodged there. These emboli can cause serious and often life-threatening complications such as myocardial infarction, stroke, seizures, and pulmonary embolism. Walker/Science Source · Antipyretics · Surgical repair of cardiac valves · Prosthetic valve replacement Myocarditis Myocarditis is an inflammation of the myocardium, or heart muscle. This uncommon condition is poorly understood because at least several weeks (in some cases a decade) elapse between exposure of the causative agent and the development of symptoms. Other causes may include allergic reactions, chemical exposure, radiation, or inflammatory disorders. Penetration of organisms, blood cells, toxins, and immune substances into the myocardium can result in muscle fiber dysfunction and degeneration that can impair contractility and conduction. Most cases of myocarditis are benign, but some result in heart failure, cardiomyopathy, dysrhythmias, and thrombi development. The patient may be asymptomatic, but when present, clinical manifestations of myocarditis include the following: · Flulike symptoms. Antipyretics, anticoagulants, antidysrhythmics, diuretics, and immunosuppressants. Increasing bed rest, restricting activity, and limiting fluids can reduce cardiac workload. The following risk factors render patients more vulnerable to development of infective endocarditis: · Intravenous drug use or presence of an intravenous catheter for an extended period · Valvular disorders · Prosthetic heart valves · Implanted cardiac devices. Infective endocarditis often requires long-term anti-infective therapy (a minimum of 4 weeks). Other treatments are initiated to maintain cardiac function and treat other symptoms: · Bed rest · Oxygen therapy application to practice Mrs. Fulcher is a 58-year-old married homemaker who was recently discharged from the hospital because of recurrent infective endocarditis. Her most recent episodes were a Staphylococcus aureus infection of the mitral valve 12 months ago and a Streptococcus mutans infection of the aortic valve 1 month ago. During her most recent hospitalization, an echocardiogram showed aortic stenosis, moderate aortic insufficiency, chronic valvular vegetation, and moderate atrial enlargement. She reports chills, fever, fatigue, joint pain, malaise, and a headache for the last 24 hours. Other routine medications ordered included furosemide (Lasix), amlodipine (Norvasc), and metoprolol (Lopressor). Additional assessment findings included a murmur; 2+ pitting tibial edema; no peripheral cyanosis; lungs sounds clear bilateral; orientation to person, place, and time but drowsiness; hematuria; and multiple petechiae on the skin of her arms, legs, and chest. What is the significance of the orthostatic hypotension, the wide pulse pressure, and tachycardia Valvular Disorders Valvular disorders cause disruption of normal blood flow through the heart. These disorders are distinguished based one the valve affected and the type of alteration. When the valves are stenosed, blood moving through the valve is reduced, causing blood to back up in the chamber just before the valve. Atresia refers to a lack of the valve opening that would otherwise allow blood flow. Pressures in the overfilled chambers increase to pump against the resistance of the stenosed valve. Because the heart (specifically the chamber) is working harder, hypertrophy of the chambers develops. Decreased cardiac output diminishes blood delivery to the coronary arteries that supply the heart. Regurgitation, also called insufficiency or incompetence, occurs when the valve leaflets do not completely close. Normally, heart valves allow blood to flow in one direction; incompetent valves, however, allow blood to flow in both directions. This regurgitation of blood increases the amount of blood that must be pumped and, in turn, the cardiac workload. The increased workload contributes to hypertrophy developing in the affected chambers. Additionally, the increased blood volume in the heart causes the chambers to dilate to accommodate the larger volume. Additional strategies may include the following measures: · Oxygen therapy · Low-sodium diet · Surgical valve repair. Anatomy and Physiology 85 Cardiomyopathy Cardiomyopathy generally refers to a group of conditions that weaken and enlarge the myocardium. Usually this condition starts in the left ventricle and eventually affects the right ventricle. Risk for developing dilated cardiomyopathy increases with age, and this condition is more common in African American men. Consequently, myocardial contractility is decreased, resulting in impaired systolic function and decreased cardiac output. The following clinical manifestations of dilated cardiomyopathy often develop insidiously: · · · · · · · · · · · · · · · · · · · · · Dyspnea Fatigue Nonproductive cough Orthopnea (difficulty breathing while lying down) Paroxysmal nocturnal dyspnea (difficulty breathing at night) Dysrhythmias Angina (cardiac chest pain that often occurs with exertion) Dizziness Activity intolerance Blood pressure changes Tachycardia Murmurs Abnormal lung sounds. Other management strategies include an implantable cardiac defibrillator, cardioversion, pacemaker, valvular repair, and heart transplant. Additionally, lifestyle modification includes a low-fat, low-sodium diet, tobacco cessation, physical activity, and abstinence from alcohol. Unlike dilated cardiomyopathy, which affects only systolic function, hypertrophic cardiomyopathy affects both systolic and diastolic function. This condition is more common in those persons who have a more sedentary lifestyle, and it appears to have an autosomal dominant genetic base. Hypertension, obstructive valvular disease, and thyroid disease increase the risk for developing hypertrophic cardiomyopathy. The hypertrophied ventricle wall becomes stiff and unable to relax during ventricular filling. With a reduction in ventricular filling, cardiac output decreases while atrial and pulmonary pressures increase. Hypertrophic cardiomyopathy is a common cause of sudden cardiac death in young people, especially young athletes. Treatment is mainly supportive, focusing on relieving heart failure symptoms by decreasing afterload and enhancing contractility. Treatment goals include reducing ventricular stiffness, improving ventricular filling, and enhancing cardiac output. Betaadrenergic blockers and calcium-channel blockers are often included in the medication regimen. Surgical removal of excess myocardium may be necessary for those patients who do not respond well to medications. Restrictive cardiomyopathy is the least common of the cardiomyopathies, but it is Anatomy and Physiology 87 endemic in parts of South and Central America, India, Asia, and Africa. This type of cardiomyopathy is characterized by rigidity of the ventricles, leading to diastolic dysfunction. Some general manifestations of dysrhythmias include the following signs and symptoms: · · · · · · · · Palpitations Fluttering sensation Skipped beats Fatigue Confusion Syncope Dyspnea Abnormal heart rate Diagnostic procedures include those for the two previously discussed cardiomyopathies. Management focuses on treating the underlying cause, dysrhythmias, and heart failure. The prognosis with restrictive cardiomyopathy is generally poor, with death often occurring from heart failure. Normal electric conduction is referred to as sinus rhythm, whereas deviations from normal are referred to as dysrhythmias or arrhythmias. Other interventions may include an internal cardiac defibrillator, pacemaker, cardioversion, defibrillation, and ablation. Avoiding triggers such as caffeine, tobacco, and stress can decrease the occurrence and severity of some dysrhythmias. This pump inadequacy epitomizes the nursing diagnosis of decreased cardiac output, and it leads to decreased cardiac output, increased preload, and increased afterload. Reproduced from Arrhythmia recognition: the art of interpretation, courtesy of Tomas B. These mechanisms increase cardiac output in the beginning, but eventually they lead to excessive preload and afterload. Initially, the efforts to bail the water are able to keep the ship afloat, but eventually the flood of incoming water is more than can be removed. Declining cardiac output also leads to decreased renal perfusion, which activates the renin­angiotensin­aldosterone system. Ventricular hypertrophy is another compensatory mechanism, but the enlarged myocardium eventually exceeds the oxygen supply and decreases contractility. All of these compensatory mechanisms are helpful at first, but in the end they create a vicious cycle that perpetuates the heart failure. Heart failure can be categorized in several ways-systolic dysfunction, diastolic dysfunction, and mixed. Systolic dysfunction is characterized by decreased cardiac output due to decreased contractility. The causes of this decreased contractility include chronic ischemia from coronary artery disease (most common), dysrhythmias, dilated cardiomyopathy, chronic alcohol abuse, and myocarditis. Diastolic dysfunction is characterized by decreased ventricular filling from abnormal myocardial relaxation and increased left ventricular pressure. Most patients have a combination of systolic and diastolic dysfunction, known as mixed dysfunction. Leftsided heart failure is a result of ineffective left ventricular contractility. Pulmonary congestion, dyspnea, and activity intolerance develop as blood backs up in the lungs. If blood continues to accumulate, pulmonary edema and rightsided heart failure will develop. Common causes of left-sided heart failure include left ventricular infarction, hypertension, and aortic and mitral valve stenosis. Right-sided heart failure is a result of ineffective right ventricular contractility. As a consequence of this condition, blood does not move appropriately out of the right ventricle. Blood backs up first in the right atrium and then in the peripheral circulation, causing increased pressures in the peripheral capillary bed. Tissue becomes edematous, as pressures in the capillaries push fluid out of the circulatory system. The most frequent cause of right-sided failure is increased pulmonary resistance because of respiratory disease (also known as cor pulmonale). Additionally, pulmonic and tricuspid valve stenosis can strain the right side of the heart. Acute heart failure may be related to a temporary condition and resolve with treatment of that condition. Chronic heart failure, in contrast, is a progressive condition that may have exacerbations, or an acute worsening, which will require additional treatment measures. The clinical manifestations of heart failure depend on the side affected and on the severity. Backup of blood blood flow stimulates into pulmonary renin-angiotensin and vein aldosterone secretion 5. They can vary from simple to complex and involve the myocardium, heart valves, and vessels near the heart. Examples of congenital heart defects include the following conditions: · Septal defects (holes in the wall that separates the heart chambers) · Patent ductus arteriosus (failure of the ductus arteriosus [the vessel between the aorta and the pulmonary artery] to close after birth) · Valve disorders. When present, manifestations may include the following symptoms: · · · · · · · Heart murmur Dyspnea Tachypnea Cyanosis Fatigue Chest pain or discomfort Difficulty gaining weight In addition, heart failure may develop due to the increased cardiac workload as a result of the defect. Strategies may include repair with a heart catheterization or surgery, heart transplant, and medications to manage symptoms and complications. This weakening happens much like a worn spot on a tire or a bulge in an old balloon. Just like the tire and the balloon, an aneurysm can rupture when the pressure builds inside the wall or when the wall becomes too thin. When it ruptures, blood spills out of the circulatory system, also known as exsanguination. The following factors increase the risk of developing aneurysm: · · · · · · · · · Congenital weakening of the arterial wall Atherosclerosis Hypertension Dyslipidemia Diabetes mellitus Tobacco usage Advanced age Trauma Infection. With a fusiform aneurysm, the aneurysm affects the entire circumference of the vessel. A false aneurysm, in contrast, does not affect all three layers of the vessel; an example of this type is a dissecting aneurysm. Some common locations for these defective areas include the abdominal aorta, the thoracic aorta, and the cerebral, femoral, and popliteal arteries. If present, symptoms may include a pulsating mass, pain, respiratory difficulty.

Cardui mariae fructus (Milk Thistle). Lipitor.

• What is Milk Thistle?
• Are there safety concerns?
• Upset stomach (dyspepsia), when a combination of milk thistle and several other herbs is used.
• What other names is Milk Thistle known by?
• Dosing considerations for Milk Thistle.
• How does Milk Thistle work?
• Diabetes. A compound in milk thistle called silymarin appears to decrease blood sugar in people with type 2 diabetes.
• Gallbladder problems, liver disease (cirrhosis, hepatitis and other liver conditions), liver damage caused by chemicals or poisonous mushrooms, spleen disorders, swelling of the lungs (pleurisy), malaria, menstrual problems, and other conditions.
• Are there any interactions with medications?

Source: http://www.rxlist.com/script/main/art.asp?articlekey=96178

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• Rosse C, Gaddum-Rosse P, eds. Hollinshead's Textbook of Anatomy Ear, Orbit, Nose. 5th ed. Philadelphia: Lippincott- Raven; 1982:730-739.
• Temkin NR, Dikmen SS, Wilensky AJ, Keihm J, Chabal S, Winn HR. A randomized, doubleblind study of phenytoin for the prevention of post-traumatic seizures. N Engl J Med. 1990;323: 497-502.
• Phi JH, Kim SK, Cho BK, et al. Long-term surgical outcomes of temporal lobe epilepsy associated with low-grade brain tumors. Cancer 2009; 115(24):5771-5779.
• Ross J Jr: Afterload mismatch in aortic and mitral valve disease: Implications for surgical therapy, J Am Coll Cardiol 5:811-826, 1985.