No full-text available
To read the full-text of this research,
you can request a copy directly from the author.
Effect of low-level laser therapy on cholesterol and triglyceride serum levels in ICU patients: A controlled, randomized study
Abstract
Introduction: igh cholesterol serum levels increases risk of coronary artery disease. To reduce this risk, statins, which is not devoid of side effects in ICU patients, have been prescribed to inhibit the enzyme responsible for cholesterol synthesis. It was proposed that Low-level laser therapy (LLLT) may reduce cholesterol and triglyceride serum levels. This randomized, controlled study investigates the influence of LLLT on the noninvasive reduction of cholesterol and triglyceride serum levels in ICU. Materials and Methods: Twenty ICU patients, 10 in each group, were enrolled in the study. The study group used ilipo LLLT device with 4 laser pads strapped around patient abdomen emitting 650-660 nm (red) laser light. The control group received sham laser. The laser therapy sessions were done for 55 minutes, twice weekly for two successive weeks with 3 days between sessions. Blood samples were drawn prior to the laser administration. A standard lipid panel was studied before the procedure to establish a baseline and at the end of the second procedure week. The serum triglyceride and total cholesterol and low and high density lipoproteins levels before and after the LLLT were compared. Results: The total cholesterol and serum triglycerides levels in the study group revealed a statistically significant mean change of −15.43 and −13.7 respectively between study baseline and endpoint (P <0.05).
... In a similar, but this time-controlled and randomized study, Rushdi [30] showed that LLLT (four laser pads with 38 diodes laser at each pad, 650-660 nm and 1.3 W) of total energy applied on the abdomen, for 55 min, two times per week for 2 weeks, could reduce cholesterol and triglyceride Fig. 4 The summary of key findings related to kind of diet and training. The blue arrows showed the comparisons control groups× trained and the red arrows the comparisons with trained groups× trained and laser groups. ...
... The hypothesis proposed by authors [30,31] was that the LLLT could alter the mitochondrial membrane potential and the intracellular redox state with a resultant increase in ADP-ATP exchange rate. These mitochondrial changes may suppress cholesterologenesis by altering the transcription factors responsible for the expression of essential genes involved in the biosynthetic process. ...
... Results of lipid profile can be changed by alteration in dietary habits and when patients perform exercise training. However, the studies discussed [30,31] did not measure the aerobic fitness and dietary variables. In this context, our study is important because there was control of both diet and training. ...
... Their results showed a significant reduction in cholesterol and triglyceride levels. In a similar, but this time-controlled and randomized study, Rushdi [30] showed that LLLT (four laser pads with 38 diodes laser at each pad, 650–660 nm and 1.3 W) of total energy applied on the abdomen, for 55 min, two times per week for 2 weeks, could reduce cholesterol and triglycerideFig. 4 The summary of key findings related to kind of diet and training. ...
... The red arrow includes the variables cholesterol, and tryacylglicerol as the blue arrow includes all variables levels as well as reduce LDL levels while preserving HDL levels. The hypothesis proposed by authors [30, 31] was that the LLLT could alter the mitochondrial membrane potential and the intracellular redox state with a resultant increase in ADP-ATP exchange rate. These mitochondrial changes may suppress cholesterologenesis by altering the transcription factors responsible for the expression of essential genes involved in the biosynthetic process. ...
... Results of lipid profile can be changed by alteration in dietary habits and when patients perform exercise training. However, the studies discussed [30, 31] did not measure the aerobic fitness and dietary variables. In this context, our study is important because there was control of both diet and training. ...
Obesity and associated dyslipidemia is the fastest growing health problem throughout the world. The combination of exercise and low-level laser therapy (LLLT) could be a new approach to the treatment of obesity and associated disease. In this work, the effects of LLLT associated with exercises on the lipid metabolism in regular and high-fat diet rats were verified. We used 64 rats divided in eight groups with eight rats each, designed: SC, sedentary chow diet; SCL, sedentary chow diet laser, TC, trained chow diet; TCL, trained chow diet laser; SH, sedentary high-fat diet; SHL, sedentary high-fat diet laser; TH, trained high-fat diet; and THL, trained high-fat diet laser. The exercise used was swimming during 8 weeks/90 min daily and LLLT (GA-Al-As, 830 nm) dose of 4.7 J/point and total energy 9.4 J per animal, applied to both gastrocnemius muscles after exercise. We analyzed biochemical parameters, percentage of fat, hepatic and muscular glycogen and relative mass of tissue, and weight percentage gain. The statistical test used was ANOVA, with post hoc Tukey-Kramer for multiple analysis between groups, and the significant level was p < 0.001, p < 0.01, and p < 0.05. LLLT decreased the total cholesterol (p < 0.05), triglycerides (p < 0.01), low-density lipoprotein cholesterol (p < 0.05), and relative mass of fat tissue (p < 0.05), suggesting increased metabolic activity and altered lipid pathways. The combination of exercise and LLLT increased the benefits of exercise alone. However, LLLT without exercise tended to increase body weight and fat content. LLLT may be a valuable addition to a regimen of diet and exercise for weight reduction and dyslipidemic control.
... Said and Elnhas came to the conclusion that LLLT applied to the abdomen has reported a substantial drop in TG, TC, and LDL with percentages of improvement (decrease) 13.26%, 7.28%, and 6.79%, respectively, and nonsignificant effect on HDL (28) and are therefore in keeping with prior results (19,(29)(30)(31)(32)(33). This somewhat matches our findings, however we observed a higher percentage of improvement, and HDL levels greatly improved, correlating with previous studies that also showed a considerable rise in HDL (34)(35)(36). ...
... It might be accounted for by the possibility that the LLLT could modify the intracellular redox state and the potential of the mitochondria membrane, leading to an increase in the rate of ADP-ATP exchange. By modifying the transcription factors necessary for the expression of crucial genes involved in the biosynthetic pathway, these mitochondrial alterations may decrease cholesterol genesis (19,29). ...
Objective: to investigate the low level laser therapy (LLLT) efficiency by using laser watch as an adjunctive therapy of dyslipidemia in type 2 diabetes mellitus (T2DM) patients. Methods: The study included sixty adult patients with diabetic dyslipidemia of both gender. They were split into two groups. Study group received anti diabetic drugs along with laser watch therapy (3 sessions /week for 12 weeks), while control group received only anti diabetic drugs. Blood sugar (FBS, 2HPP and HbA1C) and lipid panel (TG, TC, LDL and HDL) were measured before and at completion of the study. Results: A significant improvement in blood sugar and serum lipid profile was seen in both groups (P < 0.001), the study group, however, displayed more significant outcomes (P < 0.001). Conclusion: LLLT using laser watch can be used as a complementary treatment for dyslipidemia in T2DM patients to improve blood lipid profile and blood sugar.
... Figure 2 shows the cell signaling and downstream effects caused by photon absorption in the mitochondria. In this article we will mainly focus on several studies that have been reported on LLLT's use in liposuction [20,[23][24][25], noninvasive body contouring and fat reduction [26][27][28][29][30][31][32][33], reduction of cellulites [26,27,31], and reduction in serum cholesterol and triglyceride levels [34,35]. ...
... Although it had been hypothesized that fat released following LLLT treatment may appear in the bloodstream where it might adversely affect the lipid profile, a nonrandomized, uncontrolled pilot study demonstrated an actual reduction in serum cholesterol and leptin levels following LLLT [56]. Two other studies by Rushdi [35] and Jackson et al. [34] demonstrated similar effects in blood lipid profiles following LLLT treatments using i-lipo (Chromogenex, South Wales, United Kingdom) and Erchonia Zerona (Erchonia Medical, Inc.) devices, respectively. ...
Background and objective:
Low-level laser (light) therapy (LLLT) is a noninvasive, nonthermal approach to disorders requiring reduction of pain and inflammation and stimulation of healing and tissue regeneration. Within the last decade, LLLT started being investigated as an adjuvant to liposuction, for noninvasive body contouring, reduction of cellulite, and improvement of blood lipid profile. LLLT may also aid autologous fat transfer procedures by enhancing the viability of adipocytes. However the underlying mechanism of actions for such effects still seems to be unclear. It is important, therefore, to understand the potential efficacy and proposed mechanism of actions of this new procedure for fat reduction.
Materials and methods:
A review of the literature associated with applications of LLLT related to fat layer reduction was performed to evaluate the findings from pre-clinical and clinical studies with respect to the mechanism of action, efficacy, and safety.
Results:
The studies as of today suggest that LLLT has a potential to be used in fat and cellulite reduction as well as in improvement of blood lipid profile without any significant side effects. One of the main proposed mechanism of actions is based upon production of transient pores in adipocytes, allowing lipids to leak out. Another is through activation of the complement cascade which could cause induction of adipocyte apoptosis and subsequent release of lipids.
Conclusion:
Although the present studies have demonstrated safety and efficacy of LLLT in fat layer reduction, studies demonstrating the efficacy of LLLT as a stand-alone procedure are still inadequate. Moreover, further studies are necessary to identify the mechanism of action.
... It might be explained by the likelihood that NILT alters the potential of the mitochondrial membrane and the intracellular redox state, which would raise the rate of ADP-ATP exchange. These modifications to the mitochondria may reduce cholesterol synthesis by altering the transcription factors required to express important genes involved in the biosynthesis pathway [17]. The study of Ahrabi B. et al. [7] agrees with our study as it has demonstrated that lasers can be useful in lowering ROS levels, fibrosis factors, and inflammatory reactions. ...
INTRODUCTION. Metabolic syndrome (MetS) represents an assortment of interconnected metabolic risk factors, particularly central obesity, dyslipidemia, and hyperglycemia. These variables have a detrimental impact on renal function and contribute to increased mortality. This timeline necessitates a prompt approach that enables the deployment of safe and non-intrusive therapeutic equipment in conjunction with therapy for MetS patients. Accordingly, we aim to investigate whether using a low-level laser (LLL) watch device as a non-invasive instrument enhances multiple metabolic parameters, so it may be a practical therapeutic approach for managing metabolic disorders. AIM. To investigate the effect of non-invasive laser therapy on parameters of lipid profile and renal function in patients with metabolic syndrome. MATERIALS AND METHODS. This study enrolled 40 MetS patients of both genders aged 45–65 years. The study group received a 12-week treatment consisting of oral hypoglycemic medication and LLL therapy (LLLT), which involved three weekly sessions performed in the morning, targeting the wrist area using a continual output diode laser (skin contact mode, maximum power: 0.005 W, beam spot area: 0.03 cm2, energy density: 288 J/cm3, and radiation time: 1800 s). The control group only received hypoglycemia medications. Laboratory lipid profile and renal function measurements were conducted prior to and following the trial. RESULTS. Following a 12-week laser watch therapy, the results revealed a significant decline in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein (LDL) levels and an increase in high-density lipoprotein (HDL) levels, which was slightly improved in the control (p 0.00). Moreover, glomerular filtration rate (GFR) and creatinine levels were significantly improved, while the control group did not experience any significant improvement (p 0.5). DISCUSSION. Combining non-invasive laser therapy with hypoglycemic medications significantly improved the lipid profile in patients with MetS; however, kidney function, like GFR and creatinine levels, was enhanced. Furthermore, lower TC and TG levels might be due to the reduction of glycation and promoted LDL receptors which increased LDL catabolism. CONCLUSION. Non-invasive laser therapy enhances lipid profile and renal function in MetS patients. Furthermore, the control group had a minimal effect on the lipid profile and no effect on renal function.
... The therapies were reported be effective in clinical practice, such as laser therapy [4][5][6], hypolipidemic 30 drugs [7]. Low-level laser therapy (LLLT) has been found to modulate various biological processes with- 31 out side effects. ...
Background:
Laser therapy is reported to be clinically effective for improving microcirculation, rheological properties and blood lipid profiles despite the lack of certainty on the mechanism.
Objective:
This study intends to provide methods to drop blood lipid level of hyperlipidemia samples by low-intensity laser irradiation therapy and provide reasoning of mechanism.
Methods:
Twenty whole blood samples of high level of lipids profile are irradiated by 405 nm low-intensity laser at 12 J/cm2 twice a day for 3 days and compared with normal lipids profile group. Then whole blood sample are centrifuged to obtain result of erythrocyte for further interpretation. Multi-scan spectrum microplate reader is used to measure absorption spectrum and data is analyzed by software SPSS 14.0.
Results:
Results show that after 405 nm low-intensity laser irradiation, whole blood samples of high lipid level statistically have higher absorbance peak value than normal samples while erythrocyte samples have lower absorbance peak value.
Conclusions:
From the divergence of absorption peak value change after low-intensity laser irradiation for whole blood sample and erythrocyte, we suspect that low level laser irradiation affects the enzymes activity of lipid metabolism, improves the cholesterol balance of plasma and cytoplasm in erythrocyte, and decreases aggregation of the erythrocyte.
... Alternatively, released lipids may be transported via the lymphatic system to the liver where they undergo normal fatty acid oxidation. Clinically, the use of PBM has been associated with decreased plasma triglycerides and cholesterol (Jackson et al., 2010;Maloney et al., 2010;Rushdi et al, 2010). Importantly, PBM does not result in necrosis; preserves the endocrine functions of adipose tissue (Poulos and Hausman, 2010) and prevents inflammatory of high-intensity focused ultrasound (Biermann et al., 2010;Burks et al., 2011) and cryolipolysis (Avram and Harry, 2009). ...
Research into photobiomodulation reveals beneficial effects of light therapy for a rapidly expanding list of medical conditions and illnesses. Although it has become more widely accepted by the mainstream medicine, the effects and mechanisms of action appear to be poorly understood. The therapeutic benefits of photobiomodulation using low-energy red lasers extend far beyond superficial applications, with a well-described physics allowing an understanding of how red lasers of certain optimum intensities may cross the cranium. We now have a model for explaining potential therapeusis for applications in functional neurology that include stroke, traumatic brain injury, and neurodegenerative conditions in addition to the currently approved functions in lipolysis, in onychomycosis treatment, and in pain management.
... Reduction in cholesterol and leptin levels are other significant clinical benefits of LLLT which were reported in several studies. 11,12 US Food and Drug Administration (FDA) approved the clinically tested LLL ZERONA ® device as a "non-invasive dermatological aesthetic treatment for the circumferential reduction of hips, waist, and thighs. " Laser irradiation mechanism of action on non-invasive body contouring and cellulite reduction remains somewhat controversial. ...
Introduction: The objective of this study was to assess the efficacy of a combination of 3 wavelengths (including red, infra-red, and blue) of low-level laser (LLL) as a non-invasive therapeutic method to reduce abdominal girth. To achieve biochemical activity on adipocytes, a red laser was used in our selective laser combination. Near-infrared laser was used to increase depth of penetration. Nitrosyl complexes of hemoglobin (NO-Hb) are sensitive to blue light, thereby leading to increase in release of biologically active nitric oxide (NO), which can affect tissue perfusion. Thus, a blue LED was added to the laser combination. Methods: Eighteen females participated in the study. Twelve sessions of laser therapy were performed, 2 sessions per week for each subject. Continuous wave diode lasers, including red (630 nm), infra-red (808 nm), and a blue LED (450 nm) were applied and were all designed by the Canadian Optic and Laser Center. Results: Statistical analyses revealed that upper abdomen size significantly decreased from pre- (91.86 ± 11.16) to post- (87.41 ± 10.52) low-level laser therapy (LLLT) (P<0.001). Middle abdomen size showed significant reduction from pre- (97.02 ± 8.82) to post- (91.97 ± 8.49) LLLT (P<0.001). Lower abdomen size significantly decreased from pre- (100.36 ± 9.45) to post- (95.80 ± 8.52) LLLT (P<0.001). Conclusion: Based on this case series pilot investigation, the combination of 3 different wavelengths of LLL was effective for abdominal girth reduction in 100% of our subjects (P<0.001), without any side effects. Future studies will assess the long-term benefits of this laser combination for reduction of subcutaneous fat deposits.
... Cellulite grading scale: [10] and [11] (as shown in Table 1) Therapeutic Procedures: Before treatment, all patients received full explanation to the purpose of the treatment, the therapeutic and physiological benefits of this method of treatment. Each patient informed by the date and the time of her session. ...
... Several strategies have been developed to reduce MetS and CVD risk factors, for example, medication use [42], diet programs [43], physical exercise program [44] and phototherapeutic technologies such as treatments using laser [45] or light-emitting diodes (LED) [46]. The limitations of this study were: we only used anthropometric parameters and electrical bioimpedance to measure body composition and these do not distinguish between accumulations of visceral and subcutaneous abdominal fat. ...
The aim of this study was to investigate the anthropometric, metabolic, cardiovascular and symptomatic profile in gynoid and android postmenopausal women. Forty five postmenopausal women aged 50 to 60 years were divided into two groups according to fat distribution [waist-to-hip ratio (WHR)]: gynoid group (WHR between 0.68 and 0.8; N = 13) and android group (WHR > 0.8; N = 32). Body composition, skinfold thickness, serum/plasma estradiol, creatinine, urea, lipid profile, glucose and insulin, maximal exercise testing and menopause rating scale (MRS) were evaluated. The android group when compared to the gynoid group showed (P VLDL) and insulin levels with lower insulin sensitivity (%S) and greater insulin resistance (%IR) index; (iii) higher blood pressure (BP) during rest and lower maximal heart rate (HRmax) during maximal exercise testing and; (iv) higher scores of the somatic and urogenital-sexual symptoms. This study suggests that android postmenopausal women develop features that can lead to metabolic syndrome (MetS) and future cardiovascular disease (CVD), and these women may present higher scores of somatic and urogenital-sexual symptoms.
A cluster of metabolic abnormalities are markedly higher among postmenopausal women. The present study evaluated the effects of infrared-light-emitting diode (LED) during treadmill training on multiple metabolic markers, body fat, dietary habits and quality of life in postmenopausal women. Forty five postmenopausal women aged 50 to 60 years were randomly assigned to one of three groups; thirty women successfully completed the full study. The three groups were: (i) the LED group, which performed treadmill training associated with phototherapy (n=10); (ii) the exercise group, which carried out treadmill training only (n=10) and; (iii) the sedentary group, which neither performed physical training nor underwent phototherapy (n=10). Training was performed over a period of 6 months, twice a week for 45 minutes per session at 85% to 90% of maximal heart rate (HRmax), which was obtained during a progressive exercise testing. The average HR and velocity during treadmill training was 144±9 bpm and 5.8±1.3 Km/h for both trained groups. The irradiation parameters were 100 mW, 39 mW/cm² and 108 J/cm² for 45 minutes. Anthropometric data, skinfolds, biochemical exams (lipid profile, glucose and insulin), dietary habits and Women’s Health Questionnaire (WHQ) were performed. The sum of skinfolds significantly improved in the exercise and sedentary groups (p<0.05). Additionally, there was an improvement in lipid profile, particularly, total cholesterol and low-density lipoprotein (LDL) which reduced significantly for all groups (p˂0.05). However, saturated fat intake was significantly reduced in the sedentary group only (p<0.05). Quality of life improved in the LED group only, with a significant reduction in the total WHQ score (p<0.05). Physical training with or without phototherapy may improve metabolic profile. In addition, phototherapy together with treadmill training prevented an increase in subcutaneous fat and facilitated improved quality of life in postmenopausal women.
Background: Non-thermal laser therapy in dermatology, is a growing medical technology by which therapeutic effects are achieved by exposing tissues to specific wavelengths of light. Objectives: The purpose of this review was to gain a better understanding of the science behind non-thermal laser and the evidence supporting its use in dermatology.
Methods: A group of dermatologists and surgeons recently convened to review the evidence supporting the use of non-thermal laser for body sculpting, improving the appearance of cellulite, and treating onychomycosis.
Results: The use of non-thermal laser for body sculpting is supported by three randomized, double-blind, sham-controlled studies (N=161), one prospective open-label study (N=54), and two retrospective studies (N=775). Non-thermal laser application for improving the appearance of cellulite is supported by one randomized, double-blind, sham-controlled study (N=38). The use of non-thermal laser for the treatment of onychomycosis is supported by an analysis of three non-randomized, open-label studies demonstrating clinical improvement of nails (N=292).
Conclusions: Non-thermal laser is steadily moving into mainstream medical practice, such as for dermatology. Although the present studies have demonstrated safety and efficacy of non-thermal laser for body-sculpting, cellulite reduction and onychomycosis treatment, studies demonstrating the efficacy of non-thermal laser as a stand-alone procedure are still inadequate.
Low level light (or laser) therapy (LLLT) is a rapidly growing modality used in physical therapy, chiropractic, sports medicine and increasingly in mainstream medicine. LLLT is used to increase wound healing and tissue regeneration, to relieve pain and inflammation, to prevent tissue death, to mitigate degeneration in many neurological indications. While some agreement has emerged on the best wavelengths of light and a range of acceptable dosages to be used (irradiance and fluence), there is no agreement on whether continuous wave or pulsed light is best and on what factors govern the pulse parameters to be chosen.
The published peer-reviewed literature was reviewed between 1970 and 2010.
The basic molecular and cellular mechanisms of LLLT are discussed. The type of pulsed light sources available and the parameters that govern their pulse structure are outlined. Studies that have compared continuous wave and pulsed light in both animals and patients are reviewed. Frequencies used in other pulsed modalities used in physical therapy and biomedicine are compared to those used in LLLT.
There is some evidence that pulsed light does have effects that are different from those of continuous wave light. However further work is needed to define these effects for different disease conditions and pulse structures.
The use of low levels of visible or near infrared light for reducing pain, inflammation and edema, promoting healing of wounds, deeper tissues and nerves, and preventing cell death and tissue damage has been known for over forty years since the invention of lasers. Despite many reports of positive findings from experiments conducted in vitro, in animal models and in randomized controlled clinical trials, LLLT remains controversial in mainstream medicine. The biochemical mechanisms underlying the positive effects are incompletely understood, and the complexity of rationally choosing amongst a large number of illumination parameters such as wavelength, fluence, power density, pulse structure and treatment timing has led to the publication of a number of negative studies as well as many positive ones. A biphasic dose response has been frequently observed where low levels of light have a much better effect on stimulating and repairing tissues than higher levels of light. The so-called Arndt-Schulz curve is frequently used to describe this biphasic dose response. This review will cover the molecular and cellular mechanisms in LLLT, and describe some of our recent results in vitro and in vivo that provide scientific explanations for this biphasic dose response.
Lowering the blood cholesterol level may reduce the risk of coronary heart disease. This double-blind study was designed to determine whether the administration of pravastatin to men with hypercholesterolemia and no history of myocardial infarction reduced the combined incidence of nonfatal myocardial infarction and death from coronary heart disease.
We randomly assigned 6595 men, 45 to 64 years of age, with a mean (+/- SD) plasma cholesterol level of 272 +/- 23 mg per deciliter (7.0 +/- 0.6 mmol per liter) to receive pravastatin (40 mg each evening) or placebo. The average follow-up period was 4.9 years. Medical records, electrocardiographic recordings, and the national death registry were used to determine the clinical end points.
Pravastatin lowered plasma cholesterol levels by 20 percent and low-density-lipoprotein cholesterol levels by 26 percent, whereas there was no change with placebo. There were 248 definite coronary events (specified as nonfatal myocardial infarction or death from coronary heart disease) in the placebo group, and 174 in the pravastatin group (relative reduction in risk with pravastatin, 31 percent; 95 percent confidence interval, 17 to 43 percent; P < 0.001). There were similar reductions in the risk of definite nonfatal myocardial infarctions (31 percent reduction, P < 0.001), death from coronary heart disease (definite cases alone: 28 percent reduction, P = 0.13; definite plus suspected cases: 33 percent reduction, P = 0.042), and death from all cardiovascular causes (32 percent reduction, P = 0.033). There was no excess of deaths from noncardiovascular causes in the pravastatin group. We observed a 22 percent reduction in the risk of death from any cause in the pravastatin group (95 percent confidence interval, 0 to 40 percent; P = 0.051).
Treatment with pravastatin significantly reduced the incidence of myocardial infarction and death from cardiovascular causes without adversely affecting the risk of death from noncardiovascular causes in men with moderate hypercholesterolemia and no history of myocardial infarction.
Irradiation of Escherichia coli cells with either coherent or non-coherent 632.8 nm light (4 J cm-2) causes a transient acceleration of cell proliferation, which is maximal about 60 min after the end of the phototreatment. The stimulatory effect is dose dependent and is especially evident in the case of defective E. coli strains which are in the logarithmic phase of growth, while it becomes less important when cells are exposed to non-coherent 600-700 nm light. Stimulated cells exhibit biochemical and morphological changes, such as an intensified synthesis of cytoplasmic membrane proteins, increased cell volume and ribosomal content, which are suggestive of an enhanced cell metabolism.
This review focuses on the regulation of transcription factors, many of which are DNA-binding proteins that recognize cis-regulatory elements of target genes and are the most direct regulators of gene transcription. Transcription factors serve as integration centres of the different signal-transduction pathways affecting a given gene. It is obvious that the regulation of these regulators themselves is of crucial importance for differential gene expression during development and in terminally differentiated cells. Transcription factors can be regulated at two, principally different, levels, namely concentration and activity, each of which can be modulated in a variety of ways. The concentrations of transcription factors, as of intracellular proteins in general, may be regulated at any of the steps leading from DNA to protein, including transcription, RNA processing, mRNA degradation and translation. The activity of a transcription factor is often regulated by (de) phosphorylation, which may affect different functions, e.g. nuclear localization DNA binding and trans-activation. Ligand binding is another mode of transcription-factor activation. It is typical for the large super-family of nuclear hormone receptors. Heterodimerization between transcription factors adds another dimension to the regulatory diversity and signal integration. Finally, non-DNA-binding (accessory) factors may mediate a diverse range of functions, e.g. serving as a bridge between the transcription factor and the basal transcription machinery, stabilizing the DNA-binding complex or changing the specificity of the target sequence recognition. The present review presents an overview of different modes of transcription-factor regulation, each illustrated by typical examples.
Although it is generally accepted that lowering elevated serum levels of low-density lipoprotein (LDL) cholesterol in patients with coronary heart disease is beneficial, there are few data to guide decisions about therapy for patients whose primary lipid abnormality is a low level of high-density lipoprotein (HDL) cholesterol.
We conducted a double-blind trial comparing gemfibrozil (1200 mg per day) with placebo in 2531 men with coronary heart disease, an HDL cholesterol level of 40 mg per deciliter (1.0 mmol per liter) or less, and an LDL cholesterol level of 140 mg per deciliter (3.6 mmol per liter) or less. The primary study outcome was nonfatal myocardial infarction or death from coronary causes.
The median follow-up was 5.1 years. At one year, the mean HDL cholesterol level was 6 percent higher, the mean triglyceride level was 31 percent lower, and the mean total cholesterol level was 4 percent lower in the gemfibrozil group than in the placebo group. LDL cholesterol levels did not differ significantly between the groups. A primary event occurred in 275 of the 1267 patients assigned to placebo (21.7 percent) and in 219 of the 1264 patients assigned to gemfibrozil (17.3 percent). The overall reduction in the risk of an event was 4.4 percentage points, and the reduction in relative risk was 22 percent (95 percent confidence interval, 7 to 35 percent; P=0.006). We observed a 24 percent reduction in the combined outcome of death from coronary heart disease, nonfatal myocardial infarction, and stroke (P< 0.001). There were no significant differences in the rates of coronary revascularization, hospitalization for unstable angina, death from any cause, and cancer.
Gemfibrozil therapy resulted in a significant reduction in the risk of major cardiovascular events in patients with coronary disease whose primary lipid abnormality was a low HDL cholesterol level. The findings suggest that the rate of coronary events is reduced by raising HDL cholesterol levels and lowering levels of triglycerides without lowering LDL cholesterol levels.
Patients with diabetes mellitus (DM) have a marked increase in coronary heart disease (CHD) events relative to those without DM. In a previous report from the Scandinavian Simvastatin Survival Study using a clinical case definition of DM (n = 202), simvastatin-treated patients had significantly fewer CHD events compared with placebo-treated control subjects.
To examine the effect of simvastatin therapy on CHD in patients with DM and impaired fasting glucose levels.
Using the 1997 American Diabetes Association diagnostic criteria, we assessed the effect of simvastatin therapy post hoc for an average of 5.4 years in Scandinavian Simvastatin Survival Study patients with normal fasting glucose (n = 3237), impaired fasting glucose (n = 678), and DM (n = 483).
Simvastatin-treated patients with DM had significantly reduced numbers of major coronary events (relative risk [RR] = 0.58; P = .001) and revascularizations (RR = 0.52; P = .005). Total (RR = 0.79; P = .34) and coronary (RR = 0.72; P = .26) mortality were also reduced in DM, but not significantly, due to small sample size. In impaired fasting glucose (IFG) subjects, simvastatin use significantly reduced the number of major coronary events (RR = 0.62; P = .003), revascularizations (RR = 0.57; P = .009), and total (RR = 0.57; P = .02) and coronary (RR = 0.45; P = .007) mortality.
Our results extend previous findings in patients with DM to a larger cohort, confirming the benefit of cholesterol lowering with simvastatin treatment on CHD events. In addition, significant decreases in total mortality, major coronary events, and revascularizations were observed in simvastatin-treated patients with impaired fasting glucose levels. These results strongly support the concept that cholesterol lowering with simvastatin therapy improves the prognosis of patients with elevated fasting glucose levels (> or =6.0 mmol/L [> or =110 mg/ dL]) or DM and known CHD.
Based on observational and interventional data for middle-aged cohorts (aged 40-64 years), serum cholesterol level is known to be an established major risk factor for coronary heart disease (CHD). However, findings for younger people are limited, and the value of detecting and treating hypercholesterolemia in younger adults is debated.
To evaluate the long-term impact of unfavorable serum cholesterol levels on risk of death from CHD, cardiovascular disease (CVD), and all causes.
Three prospective studies, from which were selected 3 cohorts of younger men with baseline serum cholesterol level measurements and no history of diabetes mellitus or myocardial infarction. A total of 11,017 men aged 18 through 39 years screened in 1967-1973 for the Chicago Heart Association Detection Project in Industry (CHA); 1266 men aged 25 through 39 years examined in 1959-1963 in the Peoples Gas Company Study (PG); and 69,205 men aged 35 through 39 years screened in 1973-1975 for the Multiple Risk Factor Intervention Trial (MRFIT).
Cause-specific mortality during 25 (CHA), 34 (PG), and 16 (MRFIT) years of follow-up; mortality risks; and estimated life expectancy in relation to baseline serum cholesterol levels.
Death due to CHD accounted for 26%, 34%, and 28% of all deaths in the CHA, PG, and MRFIT cohorts, respectively; and CVD death for 34%, 42%, and 39% of deaths in the same cohorts, respectively. Men in all 3 cohorts with unfavorable serum cholesterol levels (200-239 mg/dL [5.17-6.18 mmol/L] and >/=240 mg/dL [>/=6.21 mmol/L]) had strong gradients of relative mortality risk. For men with serum cholesterol levels of 240 mg/dL or greater (>/=6.21 mmol/L) vs favorable levels (<200 mg/dL [<5.17 mmol/L]), CHD mortality risk was 2.15 to 3.63 times greater; CVD disease mortality risk was 2.10 to 2.87 times greater; and all-cause mortality was 1.31 to 1.49 times greater. Hypercholesterolemic men had age-adjusted absolute risk of CHD death of 59 per 1000 men in 25 years (CHA cohort), 90 per 1000 men in 34 years (PG cohort), and 15 per 1000 men in 16 years (MRFIT cohort). Absolute excess risk was 43.6 per 1000 men (CHA), 81.4 per 1000 men (PG), and 12.1 per 1000 men (MRFIT). Men with favorable baseline serum cholesterol levels had an estimated greater life expectancy of 3.8 to 8.7 years.
These results demonstrate a continuous, graded relationship of serum cholesterol level to long-term risk of CHD, CVD, and all-cause mortality, substantial absolute risk and absolute excess risk of CHD and CVD death for younger men with elevated serum cholesterol levels, and longer estimated life expectancy for younger men with favorable serum cholesterol levels. JAMA. 2000;284:311-318
Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke.
We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat.
Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability.
Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.
Mechanisms of low-power laser light action on cellular level were discussed. It was shown that coherent effects in the light-cells interaction occured at intensities ≥2×1015. The results showed that biological responses of cells to visible and near-infrared radiation occured due to physical and/or chemical changes in photoacceptor molecules.
We have seen that there is no simple answer to the question 'what controls respiration?' The answer varies with (a) the size of the system examined (mitochondria, cell or organ), (b) the conditions (rate of ATP use, level of hormonal stimulation), and (c) the particular organ examined. Of the various theories of control of respiration outlined in the introduction the ideas of Chance & Williams (1955, 1956) give the basic mechanism of how respiration is regulated. Increased ATP usage can cause increased respiration and ATP synthesis by mass action in all the main tissues. Superimposed on this basic mechanism is calcium control of matrix dehydrogenases (at least in heart and liver), and possibly also of the respiratory chain (at least in liver) and ATP synthase (at least in heart). In many tissues calcium also stimulates ATP usage directly; thus calcium may stimulate energy metabolism at (at least) four possible sites, the importance of each regulation varying with tissue. Regulation of multiple sites may occur (from a teleological point of view) because: (a) energy metabolism is branched and thus proportionate regulation of branches is required in order to maintain constant fluxes to branches (e.g. to proton leak or different ATP uses); and/or (b) control over fluxes is shared by a number of reactions, so that large increases in flux requires stimulation at multiple sites because each site has relatively little control. Control may be distributed throughout energy metabolism, possibly due to the necessity of minimizing cell protein levels (see Brown, 1991). The idea that energy metabolism is regulated by energy charge (as proposed by Atkinson, 1968, 1977) is misleading in mammals. Neither mitochondrial ATP synthesis nor cellular ATP usage is a unique function of energy charge as AMP is not a significant regulator (see for example Erecinska et al., 1977). The near-equilibrium hypothesis of Klingenberg (1961) and Erecinska & Wilson (1982) is partially correct in that oxidative phosphorylation is often close to equilibrium (apart from cytochrome oxidase) and as a consequence respiration and ATP synthesis are mainly regulated by (a) the phosphorylation potential, and (b) the NADH/NAD+ ratio. However, oxidative phosphorylation is not always close to equilibrium, at least in isolated mitochondria, and relative proximity to equilibrium does not prevent the respiratory chain, the proton leak, the ATP synthase and ANC having significant control over the fluxes. Thus in some conditions respiration rate correlates better with [ADP] than with phosphorylation potential, and may be relatively insensitive to mitochondrial NADH/NAD+ ratio.(ABSTRACT TRUNCATED AT 400 WORDS)
To assess in diabetic patients with coronary heart disease (CHD) the effect of cholesterol lowering with simvastatin on mortality and the risk of CHD and other atherosclerotic events.
A post hoc subgroup analysis was carried out on data from 202 diabetic patients and 4,242 nondiabetic patients with previous myocardial infarction or angina pectoris, serum total cholesterol 5.5-8.0 mmol/l, and serum triglycerides < or = 2.5 mmol/l who were participating in the Scandinavian Simvastatin Survival Study (4S). Participants in the 4S were randomly assigned to double-blind treatment with simvastatin, 20 mg daily, with blinded dosage titration up to 40 mg daily, according to cholesterol response during the first 6-18 weeks, or placebo. Endpoints were 1) total mortality, 2) major CHD events (CHD death or nonfatal myocardial infarction), 3) other acute atherosclerotic events, 4) myocardial revascularization procedures.
Over the 5.4-year median follow-up period, simvastatin treatment produced mean changes in serum lipids in diabetic patients similar to those observed in nondiabetic patients. The relative risks (RRs) of main endpoints in simvastatin-treated diabetic patients were as follows: total mortality 0.57 (95% CI, 0.30-1.08; P = 0.087), major CHD events 0.45 (95% CI, 0.27-0.74; P = 0.002), and any atherosclerotic event 0.63 (95% CI, 0.43-0.92; P = 0.018). The corresponding RRs in nondiabetic patients were the following: 0.71 (95% CI, 0.58-0.87; P = 0.001), 0.68 (95% CI, 0.60-0.77; P < 0.0001), and 0.74 (95% CI, 0.68-0.82; P < 0.0001).
The results strongly suggest that cholesterol lowering with simvastatin improves the prognosis of diabetic patients with CHD. The absolute clinical benefit achieved by cholesterol lowering may be greater in diabetic than in nondiabetic patients with CHD because diabetic patients have a higher absolute risk of recurrent CHD events and other atherosclerotic events.
Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) are a breakthrough in the treatment of high serum cholesterol. Several recent clinical trials1 2 3 demonstrate that statins can substantially reduce both morbidity and mortality from CHD. They are becoming a mainstay in management of patients with established CHD (secondary prevention), and they hold promise for high-risk patients without evident CHD (primary prevention). The introduction of statins occurred about the same time as the initiation of the NCEP; this program is a national effort to increase public and professional awareness of the dangers of high serum cholesterol and to emphasize the benefits of reducing serum cholesterol concentrations. Besides the NCEP’s public health effort4 to lower serum cholesterol levels in the general public through modification of life habits, the NCEP has established guidelines for cholesterol management in both secondary prevention and high-risk primary prevention.5 6 These guidelines identify LDL cholesterol as the primary target of therapy, and they specify goals for LDL cholesterol–lowering therapy. For example, the NCEP recommended that high-risk patients who have elevated LDL cholesterol levels but not clinical CHD or other atherosclerotic disease should have their LDL cholesterol concentration reduced to <130 mg/dL.5 6 For patients with CHD or other atherosclerotic diseases, the goal of NCEP is an LDL cholesterol of ≤100 mg/dL.5 6 These therapeutic goals derive from judgments based on epidemiological data and clinical trial results available at the time of reporting.
Recent statin trials1 2 3 provide a wealth of data documenting the benefit of cholesterol-lowering therapy in both primary and secondary prevention. A major fact has been established: cholesterol lowering with statins is both safe and effective in high-risk patients. Recent statin trials amply underpin the NCEP’s promotion of efforts for decreasing coronary morbidity or mortality. Of some importance, however, is …
The corepressor CtBP (carboxyl-terminal binding protein) is involved in transcriptional pathways important for development, cell cycle regulation, and transformation. We demonstrate that CtBP binding to cellular and viral transcriptional repressors is regulated by the nicotinamide adenine dinucleotides NAD+ and NADH, with NADH being two to three orders of magnitude more effective. Levels of free nuclear nicotinamide adenine dinucleotides, determined using two-photon microscopy, correspond to the levels required for half-maximal CtBP binding and are considerably lower than those previously reported. Agents capable of increasing NADH levels stimulate CtBP binding to its partners in vivo and potentiate CtBP-mediated repression. We propose that this ability to detect changes in nuclear NAD+/NADH ratio allows CtBP to serve as a redox sensor for transcription.
Low power laser irradiation is regarded to have a significant role in triggering cellular proliferation and in treating diseases of diverse etiologies. The present work contributes to the understanding of the mechanisms of action by studying low power laser effects in human fibroblasts. Confocal laser scanning microscopy is used for irradiation and observation of the same area of interest allowing the imaging of laser effects at the single cell level and in real time. Coverslip cultures were placed in a small incubation chamber for in vivo microscopic observation. Laser stimulation of the cells was performed using the 647 nm line of the confocal laser through the objective lens of the microscope. Mitochondrial membrane potential (ΔΨm), intracellular pH, calcium alterations and generation of reactive oxygen species (ROS) were monitored using specific fluorescent vital probes. The induced effects were quantified using
digital image processing techniques. After laser irradiation, a gradual alkalinization of the cytosolic pH and an increase in mitochondrial membrane potential were observed. Recurrent spikes of intracellular calcium concentration were also triggered by laser. Reactive oxygen species were generated as a result of biostimulation. No such effects were monitored in microscopic fields other than the irradiated ones.
Both photobiomodulation (PBM) and olfactory ensheathing cells (OECs) transplantation improve recovery following spinal cord injury. However, neither the combination of these two therapies nor the effect of light on OECs has been reported. The purpose of this study was to determine the effect of light on OEC activity in vitro.
OECs were purified from adult rat olfactory bulbs and exposed to 810 nm light (150 mW; 0, 0.2, or 68 J/cm(2)). After 7-21 days in vitro, cells underwent immunocytochemistry or RNA extraction and RT-PCR.
Analysis of immunolabeling revealed a significant decrease in fibronectin expression in the cultures receiving 68 J/cm(2). Analysis of gene expression revealed a significant (P < 0.05) increase in brain derived neurotrophic factor (BDNF), glial derived neurotrophic factor (GDNF), and collagen expression in the 0.2 J/cm(2) group in comparison to the non-irradiated and 68 J/cm(2) groups. OEC proliferation was also found to significantly increase in both light treated groups in comparison to the control group (P < 0.001).
These results demonstrate that low and high dosages of PBM alter OEC activity, including upregulation of a number of neurotrophic growth factors and extracellular matrix proteins known to support neurite outgrowth. Therefore, the application of PBM in conjunction with OEC transplantation warrants consideration as a potential combination therapy for spinal cord injury.
Statinassociated myopathy
- P D Thompson
- P Clarkson
- Rhjama Karas
Thompson PD, Clarkson P, Karas RHJAMA. Statinassociated myopathy. 2003; 289(13):1681-90.