Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In recent years, many genomewide screens have been performed, to identify novel loci predisposing to various complex diseases. Often, only a portion of the collected clinical data from the study subjects is used in the actual analysis of the trait, and much of the phenotypic data is ignored. With proper consent, these data could subsequently be used in studies of common quantitative traits influencing human biology, and such a reanalysis method would be further justified by the nonbiased ascertainment of study individuals. To make our point, we report here a quantitative-trait-locus (QTL) analysis of body-mass index (BMI) and stature (i.e., height), with genotypic data from genome scans of five Finnish study groups. The combined study group was composed of 614 individuals from 247 families. Five study groups were originally ascertained in genetic studies on hypertension, obesity, osteoarthritis, migraine, and familial combined hyperlipidemia. Most of the families are from the Finnish Twin Cohort, which represents a population-wide sample. In each of the five genome scans, approximately 350 evenly spaced markers were genotyped on 22 autosomes. In analyzing the genotype data by a variance-component method, we found, on chromosome 7pter (maximum multipoint LOD score of 2.91), evidence for QTLs affecting stature, and a second locus, with suggestive evidence for linkage to stature, was detected on chromosome 9q (maximum multipoint LOD score of 2.61). Encouragingly, the locus on chromosome 7 is supported by the data reported by Hirschhorn et al. (in this issue), who used a similar method. We found no evidence for QTLs affecting BMI.
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PMID:Quantitative-trait-locus analysis of body-mass index and of stature, by combined analysis of genome scans of five Finnish study groups. 1141 Aug 40

Obesity is a multi-factorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threatening to become a global epidemic. Obese patients are at a higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, certain cancers, cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnea. Obesity is a particularly challenging clinical condition to treat, because of its complex pathophysiological basis. Indeed, body weight represents the integration of many biological and environmental components. Efforts to develop innovative anti-obesity drugs have been recently intensified. In broad terms, researchers use different distinct strategies: first, to reduce energy intake; second, to increase energy expenditure; third, to alter the partitioning of nutrients between fat and lean tissue. In the present review we concentrate on the first of these strategies, by underlining the new pharmacological tools which are presently studied.
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PMID:New pharmacological tools for obesity. 1250 54

Obesity is a life-long, progressive, life-threatening, genetically related, costly, multifactorial disease manifested by excessive fat storage. It is often accompanied by multiple comorbidities including mainly hypertension, diabetes, hyperlipidemia, hypoventilation, obstructive sleep apnea, degenerative arthritis and psychosocial impairment which influence the patients quality of life and ultimately limit their life expectancy. Conservative treatment of morbid and extreme obesity including diet, physical activity, behaviour modifications or pharmacotherapy is not effective in achieving a medically significant long-term weight loss. The costs of such therapy often exceed the costs of the surgical procedure. Surgical treatment of obesity was initiated over 50 years ago. Then the surgical methods were to lead to an increased excretion but finally did not prove useful. They were replaced by restrictive and malabsorption procedures. The first methods including vertical banded gastroplasty (VBG) were introduced in 1982 while gastric banding in 1985. The second method including gastric bypasses or biliopancreatic diversion were implemented in the years 1966-1986. There are also some methods joining these two techniques. Nowadays as a results of minimally invasive surgery development, most of the operations can be performed laparoscopically.
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PMID:[Obesity and surgery]. 1292 68

Extensive differences in the osteoporosis epidemiological pattern among geographic and ethnic groups have been reported. The evidence concerning association of multiple pregnancies, lactations, and other menstrual history factors with low bone mineral density (BMD) remains inconclusive. Previous local studies addressing these issues in Jordan are very restricted. We present a cross-sectional study of Jordanian women who visited outpatient clinics between August 2000 and August 2002 at two community hospitals in Amman City. BMD measurement was performed for all subjects, while comprehensive appraisal of clinical issues related to reproductive status and past medical history was carried out using a structured questionnaire administered to 50% of the subjects. We also attempted to examine the current hypothesis of possible influence of hyperlipidemia and thyroid abnormalities on decreased BMD. According to WHO criteria, 119 (29.6%) were identified as having osteoporosis, 176 (43.8%) were osteopenic, and 107 (26.6%) had normal BMD. The multiple-linear regression analyses at different bone sites revealed that age, years of menopause, low-density lipoprotein (LDL), and follicle-stimulating hormone (FSH) have strong independent associations with decreased BMD at all lumbar and femoral neck regions. The negative effect associated with number of children (live births) and frequency of lactations was only evident at femoral neck. Although years of menstruation, age at menopause, days of menstrual cycle, number of pregnancies, and duration of hormone replacement therapy (HRT) were positively correlated with BMD, they had weaker associations than previous variables. Moreover, in the final multivariable logistic regression model, variables which rendered significantly independent risk factors after adjustment for age and BMI were: current smokers of more that 25 cigarettes/day, postmenopausal women irrespective of HRT use, menopausal years of > or =5 year intervals, natural early menopause, gastrointestinal disease, rheumatoid arthritis, osteoarthritis, hypertension, and thyroid replacement therapy. Ever-lactation, frequent lactation of 4 or more times, duration of lactation interval of 1-6 months and clinical hyperthyroidism were significant protective factors. Hysterectomy with or without oophorectomy, premature ovarian failure, gravidity, menstrual flow pattern, family history of osteoporosis, clinical hypothyroidism, hyperlipidemia, HRT, and corticosteroids therapy were not independent predictors of osteoporosis among our population. It was concluded that the prevalence of this worldwide public health problem among the Jordanian female population is extremely high, and is even found in younger age categories compared to previous international surveys. Though, the number of pregnancies in our multiparous female population showed a negative impact on femoral neck BMD, no evidence of increased risk of osteoporosis among ever-pregnant women was noted. Conversely, the current data analysis highlight many potential risk factors including associated medical illnesses, and other hormonal alterations experienced during menopausal period. Therefore, increased health awareness and intensive screening programs are mandatory for early detection of low bone mass.
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PMID:Prevalence of osteoporosis and its reproductive risk factors among Jordanian women: a cross-sectional study. 1453 Sep 8

Obesity in adults is associated with excess mortality and excess risk of coronary heart disease, hypertension, hyperlipidemia, diabetes, gallbladder disease, certain cancers, and osteoarthritis. Overweight children often become overweight adults, and overweight in adulthood is a health risk. Although childhood overweight may not always result in excess adult health risk, immediate consequences of overweight in childhood are psychosocial and also include cardiovascular risk factors such as hypertension, high cholesterol, and abnormal glucose tolerance. The causes of obesity are poorly understood, and both the prevention and the treatment of obesity are difficult. In this context, the ability to track epidemiologic trends in overweight and obesity is important.
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PMID:Epidemiologic trends in overweight and obesity. 1471 Oct 60

Guggulsterone, derived from Commiphora mukul and used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, has been recently shown to antagonize the farnesoid X receptor and decrease the expression of bile acid-activated genes. Because activation of NF-kappaB has been closely linked with inflammatory diseases affected by guggulsterone, we postulated that it must modulate NF-kappaB activation. In the present study, we tested this hypothesis by investigating the effect of this steroid on the activation of NF-kappaB induced by inflammatory agents and carcinogens. Guggulsterone suppressed DNA binding of NF-kappaB induced by tumor necrosis factor (TNF), phorbol ester, okadaic acid, cigarette smoke condensate, hydrogen peroxide, and interleukin-1. NF-kappaB activation was not cell type-specific, because both epithelial and leukemia cells were inhibited. Guggulsterone also suppressed constitutive NF-kappaB activation expressed in most tumor cells. Through inhibition of IkappaB kinase activation, this steroid blocked IkappaBalpha phosphorylation and degradation, thus suppressing p65 phosphorylation and nuclear translocation. NF-kappaB-dependent reporter gene transcription induced by TNF, TNFR1, TRADD, TRAF2, NIK, and IKK was also blocked by guggulsterone but without affecting p65-mediated gene transcription. In addition, guggulsterone decreased the expression of gene products involved in anti-apoptosis (IAP1, xIAP, Bfl-1/A1, Bcl-2, cFLIP, and survivin), proliferation (cyclin D1 and c-Myc), and metastasis (MMP-9, COX-2, and VEGF); this correlated with enhancement of apoptosis induced by TNF and chemotherapeutic agents. Overall, our results indicate that guggulsterone suppresses NF-kappaB and NF-kappaB-regulated gene products, which may explain its anti-inflammatory activities.
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PMID:Guggulsterone inhibits NF-kappaB and IkappaBalpha kinase activation, suppresses expression of anti-apoptotic gene products, and enhances apoptosis. 1532 87

Obesity is a multifactorial, chronic disorder that has reached epidemic proportions in most industrialized countries and is threatening to become a global epidemic. Obese patients are at higher risk from coronary artery disease, hypertension, hyperlipidemia, diabetes mellitus, cancers, cerebrovascular accidents, osteoarthritis, restrictive pulmonary disease, and sleep apnoea. In particular, visceral fat accumulation is usually accompanied by insulin resistance or type 2 diabetes mellitus, hypertension, hypertriglyceridemia, high uremic acid levels, low high density lipoprotein (HDL) cholesterol to define a variously named syndrome or metabolic syndrome. Metabolic syndrome is now considered a major cardiovascular risk factor in a large percentage of population in worldwide. Both obesity and metabolic syndrome are particularly challenging clinical conditions to treat because of their complex pathophysiological basis. Indeed, body weight represents the integration of many biological and environmental components and relationships among fat and glucose tolerance or blood pressure are not completely understood. Efforts to develop innovative anti-obesity drugs, with benefits for metabolic syndrome, have been recently intensified. In general two distinct strategies can be adopted: first, to reduce energy intake; second, to increase energy expenditure. Here we review some among the most promising avenues in these two fields of drug therapy of obesity and, consequently, of metabolic syndrome.
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PMID:Emerging aspects of pharmacotherapy for obesity and metabolic syndrome. 1545 65

Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterised by calcification and ossification of soft tissues, mainly ligaments and enthesis. Although DISH often coexists with osteoarthritis, this disorder differs from primary osteoarthritis by a dissimilar prevalence within the general population, gender distribution, anatomical site of primary involvement and magnitude and distribution in the spine and the peripheral joints. Little is known about the pathogenesis of the disease and possible therapeutic interventions. Treatment should be aimed at the symptomatic relief of pain and stiffness; the prevention, retardation or arrest of progression; the treatment of associated metabolic disorders and the prevention of spontaneous or induced complications. Change of lifestyle, nutrition and therapeutic options to alleviate pain and stiffness are measures that might improve quality of life in patients affected by DISH. Control of associated metabolic disorders such as hypertension, hyperinsulinaemia with or without hyperglycaemia, hyperlipidaemia and hyperuricaemia may reduce the morbidities associated with these disorders and prevent further progression of the condition. Recent developments in our understanding of the molecular basis of the ligamentous and entheseal changes that lead to the development of DISH might pave the way to future, more targeted and effective therapies.
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PMID:Current therapeutic options in the management of diffuse idiopathic skeletal hyperostosis. 1601 82

Glucosamine, commonly consumed for the treatment of osteoarthritis, is classified as a nutritional supplement; however, there are few data regarding its metabolic or vascular effects. Glucosamine is a component of the hexosamine pathway, which has been implicated in the development of insulin resistance. Anecdotal reports suggest that glucosamine consumption can increase circulating cholesterol concentrations. To investigate the metabolic and vascular effects of glucosamine supplementation, we studied male and female LDL receptor-deficient mice fed a Western diet (21% fat, 0.15% cholesterol). Three groups of 6-10 mice of each gender received either no supplement, 15 mg . kg(-1) . d(-1) glucosamine (equivalent to an average human dose), or 50 mg . kg(-1) . d(-1) glucosamine added to their drinking water for 5, 10, or 20 wk. Plasma cholesterol and triglyceride concentrations increased in all mice with the addition of the Western diet. However, after 20 wk of treatment, cholesterol and triglyceride concentrations increased further in male mice consuming glucosamine compared with control groups. Glucosamine-supplemented mice had increased initiation of atherosclerosis after 5 wk; however, there was no effect on progression of atherosclerosis in either gender after longer periods of glucosamine supplementation (10 or 20 wk). Although long-term glucosamine supplementation exacerbated the hyperlipidemia in male mice, no increase in atherosclerosis occurred. Thus, glucosamine supplementation appears to be safe, with no adverse vascular consequences.
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PMID:Glucosamine supplementation accelerates early but not late atherosclerosis in LDL receptor-deficient mice. 1705 13

Guggulsterone is a plant polyphenol traditionally used to treat obesity, diabetes, hyperlipidemia, atherosclerosis, and osteoarthritis, possibly through an anti-inflammatory mechanism. Whether this steroid has any role in cancer is not known. In this study, we found that guggulsterone inhibits the proliferation of wide variety of human tumor cell types including leukemia, head and neck carcinoma, multiple myeloma, lung carcinoma, melanoma, breast carcinoma, and ovarian carcinoma. Guggulsterone also inhibited the proliferation of drug-resistant cancer cells (e.g., gleevac-resistant leukemia, dexamethasone-resistant multiple myeloma, and doxorubicin-resistant breast cancer cells). Guggulsterone suppressed the proliferation of cells through inhibition of DNA synthesis, producing cell cycle arrest in S-phase, and this arrest correlated with a decrease in the levels of cyclin D1 and cdc2 and a concomitant increase in the levels of cyclin-dependent kinase inhibitor p21 and p27. Guggulsterone-induced apoptosis as indicated by increase in the number of Annexin V- and TUNEL-positive cells, through the downregulation of anti-apoptototic products. The apoptosis induced by guggulsterone was also indicated by the activation of caspase-8, bid cleavage, cytochrome c release, caspase-9 activation, caspase-3 activation, and PARP cleavage. The apoptotic effects of guggulsterone were preceded by activation of JNK and downregulation of Akt activity. JNK was needed for guggulsterone-induced apoptosis, inasmuch as inhibition of JNK by pharmacological inhibitors or by genetic deletion of MKK4 (activator of JNK) abolished the activity. Overall, our results indicate that guggulsterone can inhibit cell proliferation and induce apoptosis through the activation of JNK, suppression of Akt, and downregulation of antiapoptotic protein expression.
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PMID:Guggulsterone inhibits tumor cell proliferation, induces S-phase arrest, and promotes apoptosis through activation of c-Jun N-terminal kinase, suppression of Akt pathway, and downregulation of antiapoptotic gene products. 1747 22


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