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As these are complex processes they may result from different mechanisms and causes discount 10 mg zocor with amex. Consequently generic 20 mg zocor, there are many theories trying to ex plain the aging process, each from its own perspective, and none of the theories can explain all details of aging. The aging theories are not mutually exclusive, especially, when oxida tive stress is considered . Mild oxidative stress is the result of normal metabolism; the resulting biomolecular damage cannot be totally repaired or removed by cellular degradation systems, like lysosomes, pro teasomes, and cytosolic and mitochondrial proteases. Since extensive research on the relation between polymorphisms likely to accelerate/decelerate the common mechanisms of aging and resistance to the oxidative stress has been neglected in almost all scientific stud ies, the data do not allow us to conclude that the oxidative theory supports the theory of programmed aging so far . However, the most recent studies support the idea that oxida tive stress is a significant marker of senescence in different species. Resistance to oxidative stress is a common trait of long-lived genetic variations in mammals and lower organisms [5, 12]. Free radical theory, oxidative stress theory and mitochondrial theory of aging Denham Harman was first to propose the free radical theory of aging in the 1950s, and ex tended the idea to implicate mitochondrial production of reactive oxygen species in 1970s, . According to this theory, enhanced and unopposed metabolism-driven oxidative stress has a major role in diverse chronic age-related diseases [13, 14, 7]. Harman first proposed that normal aging results from random deleterious damage to tissues by free radicals  and subsequently focused on mitochon dria as generators of free radicals . Halliwell and Gutteridge later suggested to rename this free radical theory of aging as the oxidative damage theory of aging , since aging and diseases are caused not only by free radicals, but also by other reactive oxygen and ni trogen species. Increases in mitochondrial energy production at the cellular level might have beneficial and/or deleterious effects . On the other hand, enhanced mitochondrial activity may increase the pro duction of superoxide, thereby aggravating the oxidative stress and further burdening the antioxidant defence system. The mitochondria are the major source of toxic oxidants, which have the potential of reacting with and destroying cell constituents and which accumulate with age. The result of this destructive activity is lowererd energy production and a body that more readily displays signs of age (e. Damaged mitochondria can cause the energy crisis in the cell, leading to senescence and aging of tissue. The gradual loss of energy experienced with age is paralleled by a decrease in a number of mitochondria per cell, as well as energy- producing efficiency of remaining mitochondria. How 334 Oxidative Stress and Chronic Degenerative Diseases - A Role for Antioxidants ever, whether this damage affects mitochondrial function or significantly modulates the physiology of aging has remained controversial [27, 28]. As already mentioned, free radicals can damage the mitochondrial inner membrane, creating a positive feedback-loop for in creased free-radical creation. Oxidative stress from endogenous or exogenous sources can trigger the chain reaction, which leads to accel erated aging process of cells and organisms. But the efficiency of autophagy to consume mal functioning mitochondria also declines with age, resulting in more mitochondria producing higher levels of superoxide . Mitochondria of older organisms are fewer in number, larg er in size and less efficient (produce less energy and more superoxide). Free radicals could also be involved in signalling responses, which subsequently stimu late pathways related to cell senescence and death, and in pro-inflammatory gene expres sion. Other theories of aging Apart from the free radical theory, the aging is explained by many other theories: The Telomere shortening hypothesis (also described as "replicative senescence," the "Hay flick phenomenon" or Hayflick limit) is based on the fact that telomeres shorten with each successive cell division. The telomere shortening hypothesis cannot explain the aging of the non-dividing cells, e. The Reproductive-cell cycle theory states that aging is regulated by reproductive hor mones, which act in an antagonistic pleiotropic manner through cell cycle signaling. This promotes growth and development early in life in order to achieve reproduction, howev er later in life, in a futile attempt to maintain reproduction, become dysregulated and drive senescence . The Wear and tear theory of aging is based on the idea that changes associated with aging result from damage by chance that accumulates over time . The wear-and-tear theories describe aging as an accumulation of damage and garbage that eventually overwhelms our ability to function. Similar are Error accumulation and Accumulative waste theories; Error accumulation theory explains aging as the results from chance events that escape proofread ing mechanisms of genetic code , according to Accumulative waste theory the aging re sults from build-up of cell waste products in time because of defective repair-removal processes. Terman,  believes that the process of aging derives from imperfect clearance of oxidatively damaged, relatively indigestible material, the accumulation of which further hinders cellular catabolic and anabolic functions (e. It describes beneficial ac tions resulting from the response of an organism to a low-intensity stressor. It has been known since the 1930s that restricting calories while maintaining adequate amounts of other nutrients can extend the lifespan in laboratory animals.
Intra-articular glucocorticosteroid injections of involved joints are beneficial in preventing or reducing localized growth disturbances (32 34 discount 40 mg zocor fast delivery,76 buy 40mg zocor,77). This was also supported by the fact that almost one- third of the patients in that study was below the third percentile for height at the time of diagnosis (66). Several studies have suggested a decline in linear height during periods of active arthritis. The final height of affected patients is closely dependent on the severity of growth suppression during active disease and on subsequent linear growth achieved after remission (66,68,89). This study also suggested that a younger age and five or more active joints are factors that correlate with a lower body mass index (91). Anemia of chronic disease is often difficult to distinguish from iron-deficiency anemia and both forms may sometimes coexist (82,97 99). Overall, the mean dietary intake for calories and essential nutrients reported by patients was found to be adequate with few exceptions for all subtypes. The pauciarticular group (12 patients) most closely matched normal expectations for dietary intake. The systemic disease group (8 patients) was found to be short for age and above average in the weight for height index. There was a less than the recommended caloric intake for age and low circulating levels of albumin, retinol binding protein, vitamin C, and zinc. Many children in the polyarticular group (14 patients) were short for age with accompanying deficiencies in vitamin A, C, and E levels and lowered zinc levels. Influence of chronic inflammation on these findings is not fully understood and discrepancies between intake and certain nutrient levels may reflect alterations in the requirements, absorption, or utilization of these nutrients in the presence of chronic inflammation (100). Also, the mean daily intake of zinc and copper did not differ between patients with active or inactive disease. As an example, flexion contractures of the lower extremities make accurate height measurement difficult to obtain, which will then affect the weight-to-height index. Of these patients, 18% had height at or below the fifth percentile for age, 15% had weight at or below the fifth percentile for age, and 9% had weight for height at or below the fifth percentile. It was undetermined whether these findings were the result of undernutrition or disease activity. Truncal obesity occurs in iatrogenic Cushing s syndrome as a result of the redis- tribution of fat predominantly to subcutaneous tissues of the abdomen, upper back (buffalo hump), and the face (moon facies). Limiting salt intake while observing a healthy diet may help to reduce weight gain but in reality this is often difficult to achieve. Combined with characteristic purple striae, hirsutism and acne, the body appearance changes dramat- ically and these cosmetic changes often become a major issue, particularly in the adolescent. Osteopenia is defined as low bone mass for skeletal age and stage of sexual maturation. Osteoporosis is the parallel loss of bone mineral content and matrix and is defined in young adults as a bone mineral density less than 2. However, there are no accepted definitions for osteopenia and osteoporosis in childhood (74,75). Localized osteopenia is commonly identified with plain X-ray studies early in the disease process, whereas generalized osteopenia and osteoporosis develop later as disease progresses and results in an increased risk for the development of pathological fractures in the vertebrae and long bones (29,74,75). Adequate vitamin D and calcium intake and weight-bearing physical activities reduce the risk for developing both conditions, whereas active inflammatory disease and chronic glucocorticosteroid use increase the risk, particularly in children with early-onset disease. Occasionally, a nasogastric tube is needed for enteral feeding of the malnourished child or total parenteral nutrition for the medically unstable patient. Other factors that need to be considered in patients with decreased intake include depression, eating disorders, neglect and abuse, and socioeconomic factors. Parents often implement unconventional dietary regimens without consulting a physician. Not only do such practices cause an economic burden, they also may be injurious and interfere with standard therapy (82,109). Sometimes, parents implement such regimens in combination with conventional therapy, but on occasion these remedies are the only therapy provided to the child, and then lead to significant adverse effects (109). Other than scattered case reports, there are no published population-based studies that estimate the prevalence of food-related chronic arthritis in the pediatric age group (82). The efficacy and safety of bispho- sphonates in children are unknown and require further evaluation with randomized, controlled, long-term trials. Muscu- loskeletal adverse effects include transient skeletal pain, epiphyseal and metaphyseal radiologic sclerosis in growing bones, and mandibular osteonecrosis. Other supplements that provide clear benefits include multivitamins and folic acid. Patients receiving methotrexate require folic acid supplementation to minimize the occurrence of oral ulcers. Control of underlying chronic inflammation usually corrects the anemia of chronic disease, however, iron supplementation may be beneficial if iron-deficiency anemia coexists (i). Occasionally, recombinant human erythropoietin is considered for the treatment of anemia in rheumatic diseases (116).
Pathophysiology The exact pathophysiology is unknown buy zocor 10mg amex, but it is clear that Group A purchase zocor 20mg with visa, beta-hemo- lytic streptococcal infections of the pharynx stimulate T-cell and B-cell lympho- cytes to produce antibodies presumably against some antigenic component of the bacteria that cross-react with an antigen on myocytes or cardiac valve tissue. There is a latent period of 2 4 weeks between the acute illness (sore throat and fever) and the development of carditis and cardiac valve damage. The mitral valve is most commonly affected, followed by the aortic valve, and damage caused by the cross-reactive antibodies leads to valvular insufficiency and later stenosis. Clinical Manifestations The Jones Criteria have been revised numerous times and are designed to be guide- lines for diagnosis. Major criteria in order of occurrence are: Arthritis: Migratory polyarthritis involving large joints, such as the knees, ankles, and elbows. The mitral regurgitation murmur is a holosystolic murmur best heard at the apex with short mid-diastolic apical murmur secondary to increased flow across the mitral valve (functional mitral stenosis). Congestive heart failure may develop in a small number of patients presenting with rheumatic carditis. The chorea is less common in adolescents and not seen in adults with rheumatic fever and almost never present simultaneously with arthritis. The presence of Sydenham s chorea is sufficient to make the diagnosis of rheumatic fever even if it is the only manifestation noted. These nodules develop at sites of trauma to the bony surfaces in patients who have active disease. Chest Radiography Chest radiography findings vary according to the clinical presentation. Cardiomegaly and increased broncho-vascular markings reflecting pulmonary venous congestion may be noted. Occasionally, intermittent 2:1 atrioventricular block or rarely complete heart block may be seen. Echocardiography Transthoracic echocardiography is a valuable tool for assessing the degree of valve regurgitation and for follow-up of rheumatic valvular lesions. It is of great value in diagnosis and grading of pericardial effusion, and if needed, pericardiocentesis may be performed at the bedside under echocardiography guidance. Color Doppler is used to assess the extent of mitral regurgitation, which is initially the result of mitral valve leaflet disease. However, in moderate to severe mitral regurgitation, the left ventricle and atrium dilate over time resulting in mitral valve annulus dilation and worsening mitral regurgitation. Mitral stenosis is a late manifestation of rheumatic fever and not seen during the acute phase of illness. The aortic valve may be involved, and echocardiography would demonstrate thickening of aortic valve cusps with regurgitation. Unlike the mitral valve, aortic valve stenosis is not noted as a complication of rheumatic fever. Cardiac Catheterization Cardiac catheterization is seldom needed in the diagnosis of cases of rheumatic heart disease. Aspirin 100 mg/kg/day divided Q4 hours for 1 week, then reduce to 75 mg/kg/day for 4 weeks, then taper over 2 weeks. In significant carditis (significant valve pathology, congestive heart failure), use steroids (prednisone 2 mg/kg/day) instead of aspirin for 2 weeks, then taper steroids over 2 weeks. Treatment of Congestive Heart Failure: most cases of mild heart failure respond well to steroid therapy and bed rest. If the patient has moderate to severe congestive heart failure, digoxin Lasix and afterload reducing agents may be needed for treatment. Treatment of Sydenham Chorea: long-term antimicrobial prophylaxis and halo- peridol treatment. Length of prophylaxis may be one of the following: Ten years after the last episode of rheumatic fever or to adulthood, whichever is longer. Case Scenarios Case 1 History: A 16-year-old female presented to her primary care physician with history of sore throat for the past few days. The patient initially described diffuse joint pain, but after careful questioning, she states that there was severe bilateral knee pain and she was unable to stand. A grade 2/6 systolic murmur at the left upper sternal border was detected by auscultation with no radiation. Management: Rheumatic fever was suspected; therefore, penicillin was prescribed to eradicate acute infection and was advised to start long-term prophylaxis for rheumatic fever. Evaluation by the pediatric cardiologist revealed similar findings through history and physical examination. Echocardiography revealed normal cardiac structure and function with no evidence of mitral or aortic valve disease. Discussion: History and physical examination in this patient do not support rheu- matic fever. The heart murmur noted in this patient is consistent with an innocent heart murmur rather than a pathological murmur.