Electromagnetic fields in the treatment of chronic lower back pain in patients with degenerative disc disease.

AIM: To examine the effects of low-amplitude, low frequency electromagnetic field therapy (EMF) therapy in patients with persistent chronic lower back pain associated with degenerative disc disease. DESIGN: Double-blind, randomized and placebo controlled. INTERVENTION: EMF using a medical device resonator; control group underwent same procedures, except the device was turned off. OUTCOME MEASURES: Pain reduction and mobility. RESULTS: Improvements in overall physical health, social functioning and reduction in bodily pain were observed in the EMF group. The pain relief rating scale showed a higher level of pain relief at the target area in the EMF group. An increase in left lateral mobility was seen only in the EMF group. CONCLUSION: EMF treatment may be of benefit to patients with chronic nonresponsive lower back pain associated with degenerative disc disease.

Functional outcomes of patients with amputation receiving chronic dialysis for end-stage renal disease.

OBJECTIVE: The aim of this study was to compare the rehabilitation length of stay and functional outcome of patients with amputation on chronic dialysis with a similar group of patients not on dialysis. DESIGN: This was a retrospective cohort study. Twenty-five patients with amputations on chronic dialysis and 25 nonrenal controls with amputation were included in the two groups. Primary outcome measures were Functional Independence Measure scores through discharge and follow-up, the percentage of patients fitted with a prosthesis, the number of patients able to ambulate independently indoors or outdoors or operate a wheelchair, and acute and rehabilitation length of stay for inpatients. Comorbidities and complications in end-stage renal disease (ESRD) patients with amputation on chronic dialysis vs. those without renal disease were also evaluated. RESULTS: Eleven women and 14 men were included in each group. The study group patients were younger than non-ESRD controls (54 ± 12 and 61 ± 11 yrs, respectively; P = 0.05). No significant differences were found between the groups in sex, race, amputation etiology, or comorbidities, except minor amputations of toes and fingers, which were performed more often in the ESRD group compared with the non-ESRD group (14 and 2, respectively; P = 0.0003). Functional Independence Measure score was higher in the non-ESRD group on discharge (112.1 ± 7.6 vs. 107.5 ± 7.7; P = 0.04) and follow-up (111.3 ± 10.7 vs. 104.4 ± 8.7; P = 0.02). The number of patients able to ambulate indoors and outdoors or operate wheelchair independently on discharge was not statistically different between the groups. Length of stay was higher in the ESRD group (153 ± 67 vs. 105 ± 42 days; P = 0.04). CONCLUSIONS: Patients with limb amputations on chronic dialysis had significantly longer length of stay and lower Functional Independence Measure scores compared with the non-ESRD group. It is suggested that current practices may need to be adjusted to accommodate the complex rehabilitation needs of the ESRD patient population.

The potential health benefits of taurine in cardiovascular disease.

Taurine (2-aminoethanesulphonic acid), a sulphur-containing amino acid, is found in most mammalian tissues. Although it can be synthesized endogenously, the major source of taurine is from the diet. Taurine was found to exhibit diverse biological actions, including protection against ischemia-reperfusion injury, modulation of intracellular calcium concentration, and antioxidant, antiatherogenic and blood pressure-lowering effects. The present review will address the potential beneficial actions of taurine in congestive heart failure, hypertension, ischemic heart disease, atherosclerosis and diabetic cardiomyopathy. There is a wealth of experimental information and some clinical evidence available in the literature suggesting that taurine could be of benefit in cardiovascular disease of different etiologies. However, double-blind long-term clinical trials need to be conducted before taurine can be unequivocally recommended as a nutritional intervention for the prevention and/or treatment of cardiovascular disease.

Targeting platelets for prevention and treatment of cardiovascular disease.

Platelets play an important role in the development of thrombosis, atherosclerosis, hypertension, heart attack and stroke. As a result, pharmacologic interventions that influence platelet functions, such as adhesion, aggregation and the release of different factors, are considered useful for the prevention and treatment of cardiovascular disease. Although classical anti-platelet agents have proven beneficial effects for the treatment of some specific cardiovascular diseases, there are limitations for their use as these drugs target platelet function directly. In contrast, newly developed anti-platelet agents have broad applications for the treatment of cardiovascular disease as they not only influence platelet function but are also considered to affect cardiac and vascular smooth muscle cell functions. Natural food products and nutraceutical agents also appear to modify cardiovascular abnormalities by affecting various platelet functions; however, the mechanisms of their actions remain to be investigated. Accordingly, this article is focused to discuss emerging pharmacologic, nutritional and nutraceutical interventions that may influence the prevention or progression of a broad range of cardiovascular diseases.

Pharmacological basis of different targets for the treatment of atherosclerosis.

The development of atherosclerotic plaque is a highly regulated and complex process which occurs as a result of structural and functional alterations in endothelial cells, smooth muscle cells (SMCs), monocytes/macrophages, T-lymphocytes and platelets. The plaque formation in the coronary arteries or rupture of the plaque in the peripheral vasculature in latter stages of atherosclerosis triggers the onset of acute ischemic events involving myocardium. Although lipid lowering with statins has been established as an important therapy for the treatment of atherosclerosis, partially beneficial effects of statins beyond decreasing lipid levels has shifted the focus to develop newer drugs that can affect directly the process of atherosclerosis. Blockade of renin angiotensin system, augmentation of nitric oxide availability, reduction of Ca(2+) influx, prevention of oxidative stress as well as attenuation of inflammation, platelet activation and SMC proliferation have been recognized as targets for drug treatment to control the development, progression and management of atherosclerosis. A major challenge for future drug development is to formulate a combination therapy affecting different targets to improve the treatment of atherosclerosis.

Disability and quality of life in Canadian aboriginal and non-aboriginal diabetic lower-extremity amputees.

OBJECTIVE: To compare and contrast disability and quality of life (QOL) in Aboriginal and non-Aboriginal subjects with diabetes who had lower-extremity amputation (LEA) and were living in urban and rural communities in Canada. DESIGN: Descriptive study using an interviewer-administered questionnaire and hospital medical record review. SETTING: Tertiary care center. PARTICIPANTS: Forty-four diabetic subjects (minimum age, 18 y) not receiving dialysis, including 21 Aboriginal (8 urban, 13 rural) and 23 non-Aboriginal (16 urban, 7 rural) subjects. Subjects were living in their current residence and had undergone LEA above the level of the ankle 6 months or more before interview. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Qualitative and quantitative data about symptoms, impairment, and QOL. RESULTS: Aboriginal subjects were younger than non-Aboriginal subjects at the time of diabetes diagnosis (Aboriginal, 42+/-10 y; non-Aboriginal, 52+/-14 y; P<.005) and first major LEA (Aboriginal, 57+/-7 y; non-Aboriginal, 64+/-11 y; P<.015). All subjects received rehabilitation after amputation. More rural non-Aboriginal subjects (83%) used their prosthesis both in and outside the home for all movements than other subjects (P<.048). Rural non-Aboriginal subjects had the lowest and urban non-Aboriginal subjects had the highest frequency of walking-aid use outside the home. Assistance with personal care was required by a minority of subjects, but assistance with daily housework was required by the majority of subjects. Qualitative analysis revealed that participants were, in most cases, comfortable with their postamputation life. CONCLUSIONS: Although the majority of participants in this study generally felt satisfied with their current status, major functional changes were noted after LEA that had a large negative impact on QOL.

Changes in skeletal muscle SR Ca2+ pump in congestive heart failure due to myocardial infarction are prevented by angiotensin II blockade.

In order to understand the mechanisms of exercise intolerance and muscle fatigue, which are commonly observed in congestive heart failure, we studied sarcoplasmic reticulum (SR) Ca(2+)-transport in the hind-leg skeletal muscle of rats subjected to myocardial infarction (MI). Sham-operated animals were used for comparison. On one hand, the maximal velocities (Vmax) for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities in skeletal muscle of rats at 8 weeks of MI were higher than those of controls. On the other hand, the Vmax values for both SR Ca(2+)-uptake and Ca(2+)-stimulated ATPase activities were decreased significantly at 16 weeks of MI when compared with controls. These alterations in Ca(2+)-transport activities were not associated with any change in the affinity (1/Ka) of the SR Ca(2+)-pump for Ca2+. Furthermore, the stimulation of SR Ca(2+)-stimulated ATPase activity by cyclic AMP-dependent protein kinase was not altered at 8 or 16 weeks of MI when compared with the respective control values. Treatment of 3-week infarcted animals with angiotensin-converting enzyme (ACE) inhibitors such as captopril, imidapril, and enalapril or an angiotensin receptor (AT1R) antagonist, losartan, for a period of 13 weeks not only attenuated changes in left ventricular function but also prevented defects in SR Ca(2+)-pump in skeletal muscle. These results indicate that the skeletal muscle SR Ca(2+)-transport is altered in a biphasic manner in heart failure due to MI. It is suggested that the initial increase in SR Ca(2+)-pump activity in skeletal muscle may be compensatory whereas the depression at late stages of MI may play a role in exercise intolerance and muscle fatigue in congestive heart failure. Furthermore, the improvements in the skeletal muscle SR Ca(2+)-transport by ACE inhibitors may be due to the decreased activity of renin-angiotensin system in congestive heart failure.

Role of cholesterol in cardiovascular dysfunction.

BACKGROUND: Hypercholesterolemia, which is characterized by high levels of lipoprotein-containing cholesterol in plasma, is generally accepted as a major risk factor for the development of atherosclerosis and subsequent myocardial ischemia. The cardiovascular effects of elevated serum cholesterol are predominantly attributed to atherosclerotic lesions in coronary arteries; however, the role of cholesterol in causing heart dysfunction without the occurrence of atherosclerosis is not fully appreciated. OBSERVATIONS: Each type of biological membrane has a specific amount of cholesterol, which is required for proper functioning of the membrane-bound enzymes and cation transporters. High levels of cholesterol have been demonstrated to cause changes in membrane structure and function independent of atherosclerosis. Particularly, alterations in membrane cholesterol content have been shown to affect myocardial contractility, excitability and conduction properties. The activities of cardiac sarcolemmal enzymes such as Na+-K+ ATPase, Mg2+ ATPase and Ca2+ pump ATPase as well as Ca2+-dependent K+ channels and Na+-Ca2+ exchanger are altered as a consequence of changes in the membrane cholesterol content. Furthermore, high levels of cholesterol are known to cause endothelial dysfunction and smooth muscle abnormalities, which occur without visible atherosclerosis lesion development. On the other hand, indirect effects of cholesterol on the cardiovascular system are evident on its oxidative modification and subsequent development of visible atherosclerotic lesions and myocardial ischemia. CONCLUSIONS: Hypercholesterolemia has been shown to cause cardiovascular dysfunction due to direct action on membrane fluidity, enzyme activities and cation transporters in the endothelial cells, vascular smooth muscle cells and cardiomyocytes. On the other hand, development of atherosclerosis by high levels of cholesterol is associated with the oxidation products of cholesterol and is thus considered to affect the cardiovascular system indirectly as a consequence of ischemic heart disease.

Therapeutic potentials of sarpogrelate in cardiovascular disease.

In view of the pivotal role of serotonin (5-HT) in a wide variety of cardiovascular disorders, extensive effort has been made to develop different types of 5-HT receptor antagonists for therapeutic use. On the basis of experimental studies, this article is focused on the potentials of sarpogrelate, a specific 5-HT2A receptor antagonist as an antiplatelet, antithrombotic, antiatherosclerotic and antianginal agent. The major effects of sarpogrelate are due to the inhibition of 5-HT-induced platelet aggregation and smooth muscle cell proliferation. This agent was found to attenuate the 5-HT-mediated increase in intracellular Ca2+ and ischemia-reperfusion injury in the heart. Sarpogrelate has been found to have beneficial effects in peripheral vascular disease, restenosis after coronary stenting, pulmonary hypertension, acute and chronic myocardial infarction.

Therapeutic potentials of pentoxifylline for treatment of cardiovascular diseases.

BACKGROUND: Cardiovascular diseases are life-threatening conditions and, thus, have received a great deal of attention over the years. Several mechanisms, including hemorheology changes and inflammatory effects, are considered to be involved in the pathogenesis of these diseases. Because cardiovascular dysfunction is also known to worsen hemorheology changes and influence vital symptoms, it has become critical to formulate effective therapeutic strategies to combat the deleterious effects of cardiovascular diseases. Although a wide variety of drugs have been developed for the treatment of cardiovascular diseases, the effectiveness of any agent for therapy of a given disease cannot be indicated with certainty. OBJECTIVES AND OBSERVATIONS: Pentoxifylline (PTXF), a phosphodiesterase inhibitor, has been investigated for close to two decades because of its primary pharmacological actions on hemorheology and other anti-inflammatory effects. Several studies have been conducted to investigate the effects and mechanisms of PTXF in ischemic injury, peripheral vascular disease and heart failure. The present article is intended to emphasize the therapeutic potentials of PTXF in different types of cardiovascular diseases, focusing on the mechanisms of its pharmacological actions.

Mechanisms of lysophosphatidic acid-induced DNA synthesis in vascular smooth muscle cells.

In order to investigate the signal transduction mechanisms of lysophosphatidic acid (LPA)-induced vascular smooth muscle (VSM) DNA synthesis, rat aortic A10 cells were used as an experimental model and [ H]-thymidine incorporation was used as an index of DNA synthesis. LPA caused dose- and time-dependent increase in DNA synthesis in A10 VSM cells. LPA (10 microM) also stimulated the activity of casein kinase II (CKII) in a time-dependent manner. The inhibitors of CKII, daidzein and 5,6-dichlorobenzimidazole riboside, diminished the LPA-induced increase in CKII activity and DNA synthesis. The LPA-stimulated activities of extracellularly regulated kinases (ERK) and p38 kinases as well as the stimulatory effects of LPA on DNA synthesis were blocked by ERK inhibitor, PD98059, and p38 kinase inhibitor, SB203580. The LPA-induced increase in intracellular free Ca and the LPA-induced DNA synthesis were not affected by Ca channel blockers, verapamil and diltiazem, as well as a Ca -dependent protein phosphatase (calcineurin) inhibitor, cyclosporine A. These data suggest that the LPA-induced DNA synthesis in VSM cells may be mediated by a signal transduction mechanism involving CKII, ERK, and p38 K.

Potential role of lysophosphatidic acid in hypertension and atherosclerosis.

BACKGROUND: Lysophosphatidic acid (LPA) is present in both serum and cytosol. Serum LPA is mainly released from platelets whereas cytosolic LPA is the metabolite of phosphatidic acid due to the action of phopholipase A2. Because platelet function and phospholipase A2 activity are upregulated in hypertensive and coronary heart disease patients, respectively, plasma and cytosolic LPA levels are expected to be higher in these pathological conditions. OBSERVATIONS: LPA is known to cause platelet aggregation and thus release more LPA as well as platelet-derived growth factor; this positive feedback circuit leads to the continuous growth of vascular smooth muscle cells (VSMCs). LPA also increases the intracellular concentration of free calcium in VSMCs and elevates the blood pressure. LPA content in the atherosclerotic plaque is elevated about 13 times in comparison with normal tissues because oxidized low-density lipoproteins promote the production of LPA. On the other hand, LPA has been shown to protect the heart from ischemia and reperfusion-induced damage due to its antiapoptosis effect. Because LPA has been reported to stimulate mitogen-activated protein kinase, phosphatidylinositide-3-kinase and protein kinase C, this bioactive phospholipid may be involved in the signal transduction mechanisms during the process of cardiac hypertrophy. CONCLUSIONS: Due to its ability to increase intracellular Ca2+ and proliferation of VSMCs, LPA may play an important role in the development of hypertension and atherosclerosis. It is therefore suggested that LPA antagonists may prove useful in the treatment of both hypertension and atherosclerosis.

Pathogenesis of atherosclerosis: A multifactorial process.

Atherosclerosis is a leading cause of mortality and morbidity in the western world. It has been recognized for over a century, and the understanding of its pathogenesis has undergone many changes. Pathophysiological studies have unravelled the interactions of molecular and cellular elements involved in atherogenesis. The focus has shifted to the novel risk factors as well as characteristics and stability of atherosclerotic plaque; the genetic predisposition has further broadened the pathogenetic mechanisms. This review focuses on the molecular mechanisms involved in the evolution of the atherosclerotic plaque that may pave the way for selecting optimal therapies and preventing plaque complications. Atherosclerosis is no longer a disease attributed mainly to the high lipid content of the body. New insight into the disease pathology has shown it to be a disease of much greater ramifications. Endothelial damage and reactive oxygen species (and other free radicals) have predominantly emerged as factors in virtually all pathways leading to the development of atherosclerosis due to hyperlipidemia, diabetes, hypertension or smoking. Novel risk factors such as hyperhomocysteinemia, infections and systemic lupus erythematosus have emerged. Atherosclerosis has come to be regarded as a chronic inflammatory disease with an autoimmune component. The genetic basis of the disease assumes significance as candidate genes are identified and gene therapy becomes a promising new addition to the existing, less substantial conventional therapies.