Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypercholesterolaemia is thought to foster atherosclerosis and impotence through its effects on vascular endothelium. In this study, we investigated the pharmacological changes in rabbit corpus cavernosum (CC) secondary to incubation with lysolecithin and hypercholesterolaemia. A daily egg yolk dietary supplement induced gross hypercholesterolaemia in our rabbits. Group A of test animals (n-12) was fed with the yolk content of single egg and group B (n-6), that from two eggs for eight weeks. Serum level estimation revealed a progressive elevation of cholesterol to 15 and 30 times respectively, in the two treated groups as compared to values in the control group (n-6). Early histological manifestations of atherosclerosis were perceived as fat cell lesions in the cavernosum of treated animals. In vitro pharmacological studies on CC strips from both groups of test animals demonstrated a profound accentuation of the contractile responses to noradrenaline and histamine and attenuation of relaxant response to acetylcholine. However, in contrast to single-egg treated group, which demonstrated a reduction in the relaxant response to electrical field stimulation (EFS), there was a marked and statistically significant potentiation of this nitrergic transmission, in the two-eggs group. Prior incubation of CC strips of normolipidaemic rabbits (n-7) with lysolecithin, reproduced similar exaggerated response to EFS. Therefore, from the results of our study, it is concluded that oxidised LDL or its major amphiphile lysolecithin, at some critical level or beyond, may be capable of reverting at least some of the adverse effects of hypercholesterolaemia on erectile function, through its mediating effect on nitrergic transmission.
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PMID:Elevated low-density lipoprotein cholesterol (LDL-C) enhances pro-erectile neurotransmission in the corpus cavernosum. 1040 85

Peripheral arterial disease (PAD) is caused by atherosclerosis, the leading cause of death and disability in patients age 50 and older. PAD progresses gradually and silently over many years, occluding the lumen of arteries that supply blood to the extremities. Symptoms of peripheral arterial insufficiency include intermittent claudication, rest pain, and impotence. Nonoperative management--including the control of risk factors such as hypertension, diabetes, hyperlipidemia, and smoking--is the most effective method to lower the risk of morbidity from PAD. Diagnostic technologies such as color duplex imaging, MRI, and MRA complement the clinical assessment of PAD and provide a stronger foundation for treatment decisions in the primary care setting.
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PMID:Peripheral arterial disease. Medical management in primary care practice. 1130 19

Gene therapy refers to the transfer of specific genes to the host tissue to intervene in a disease process, with resultant alleviation of the symptoms of a particular disease. Cardiovascular gene transfer is not only a powerful technique for studying the function of specific genes in cardiovascular biology and pathobiology, but also a novel and promising strategy for treating cardiovascular diseases. Since the mid-1990s, nitric oxide synthase (NOS), the enzyme that catalyzes the formation of nitric oxide (NO) from L-arginine, has received considerable attention as a potential candidate for cardiovascular gene therapy, because NO exerts critical and diverse functions in the cardiovascular system, and abnormalities in NO biology are apparent in a number of cardiovascular disease processes including cerebral vasospasm, atherosclerosis, postangioplasty restenosis, transplant vasculopathy, hypertension, diabetes mellitus, impotence and delayed wound healing. There are three NOS isoforms, i.e., endothelial (eNOS), neuronal (nNOS) and inducible (iNOS). All three NOS isoforms have been used in cardiovascular gene transfer studies with encouraging results. This review will discuss the rationale of NOS gene therapy in different cardiovascular disease settings and summarize the results of experimental NOS gene therapy from various animal models of cardiovascular disease to date.
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PMID:Nitric oxide synthase gene therapy for cardiovascular disease. 1223 10

Werner's syndrome is a rare autosomal recessive disease caused by the mutation of DNA helicase gene (WRN), characterized by the premature onset of multiple age-related disorders and skin changes similar to those observed in scleroderma. Some endocrinologic and metabolic disorders have been described in patients with Werner's syndrome. We report one case in a 41-year-old man issuing from consanguineous parents, who presented for exploration of hypoglycemic episodes and sexual impotence. Werner's syndrome was diagnosed on the basis of his characteristic clinical appearance. Metabolic disorders were insulin-requiring diabetes and hypertriglyceridemia. Endocrinologic investigation revealed nodular goiter, sub clinical primary hypothyroidism, hypergonadotrophic hypogonadism,adrenal cortical hypofunction and GH deficiency. Pathology examination of the skin biopsy showed a scleroderma-like aspect. Finally, osteoporosis, atherosclerosis and sub-capsular cataract were associated. Thus, in Werner's syndrome metabolic and endocrinologic investigation is necessary in order to treat these disorders and improve the patient's prognosis and life.
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PMID:[Werner's syndrome and endocrine disorders]. 1291 63

The varied biological effects of nitric oxide (NO) have led to intense research into its diverse physiologic and pathophysiologic roles in multiple disease processes. It has been implicated in the development of altered vasomotor tone, intimal hyperplasia, atherosclerosis, impotence, host defense, and wound healing. Using the modern technologies of recombinant DNA and gene transfer using adenoviral vectors, the effects of NO derived from various NO synthase (NOS) enzymes can be studied in a variety of tissues and the therapeutic applications of NOS is possible. Such uses of NOS gene transfer have been investigated extensively in the vasculature where NO is critical to regulating vascular homeostasis. NOS gene therapy has the theoretical advantage of allowing NO delivery to be localized, thereby limiting potential adverse effects of NO. The benefits of adenoviral vectors in gene transfer include relatively high transduction efficiencies, both replicating and nonreplicating cells may be infected, and the high titers of adenovirus that can be produced. The methods described in this chapter include the cloning of the iNOS cDNA into a recombinant adenoviral vector, large-scale production of that vector AdiNOS preparation, and the use of the vector to transduce tissue in vitro and in vivo.
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PMID:Adenovirus-mediated nitric oxide synthase gene transfer. 1519 49

The discovery of the multiple physiological and pathophysiological processes in which nitric oxide (NO) is involved has promoted a great number of pharmacological researches to develop new drugs that are capable of influencing NO production directly and/or indirectly for therapeutic purposes (i.e, NO-releasing drugs, NO-inhibiting drugs, and phosphodiesterase V inhibitors). In particular, the so-called NO donor drugs could actually have an important therapeutic effect in the treatment of many diseases such as arteriopathies (atherosclerosis and its sequelae, arterial hypertension and some forms of male sexual impotence), various acute and chronic inflammatory conditions (colitis, rheumatoid arthritis and tissue remodelling), and several degenerative diseases (Alzheimer's disease and cancer). The old organic nitrates show some well-known pitfalls including the induction of tolerance and acute side effects related to abrupt vasodilation such as cephalea and hypotension, which limit their therapeutic indications. A low therapeutic index (i.e., peroxynitrite toxicity) has always characterised the sydnonimines class. A series of interesting new classes of NO donors are under intense pharmacological investigation and scrutiny (S-nitrosothiols, diazeniumdiolates and NO hybrid drugs), each characterised by a particular pharmacokinetic and pharmacodynamic profile. The most important obstacle in the field of NO donor drugs is represented by the difficulty in targeting NO release, and thereby its effects, to a particular tissue.
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PMID:Nitric oxide donor drugs: an update on pathophysiology and therapeutic potential. 1602 73

Sexual dysfunction impairs the quality of life of patients undergoing hemodialysis (HD). The aim of this study was to evaluate the prevalence and the nature of sexual dysfunction in a Moroccan cohort of patients with chronic renal failure (CRF) on HD. This cross-sectional study was carried out with a questionnaire in 86 patients undergoing hemodialysis. Clinical and biological investigations were done. The mean age of our patients was 46.27 +/- 15.68 years old. 81.4% of the cases suffered from a decrease in sexual activity after the onset of HD. The decrease or the loss of libido was noted in 59.3% of the cases. Total impotence was present in 22.1% of the cases and 36% reported partial impotence. Ejaculation was present in 86% of the cases. The comparison between the group of patients who had no sexual dysfunction (group I) and the group of those who had this problem (group II) showed significant differences of age, social status and sexual life before HD. Other significant differences were found regarding frequency of intercourses and sexual satisfaction. Group II was divided into 2 subgroups: IIA included patients who had sexual dysfunction before HD and IIB: those who developed it after. The comparison of this subgroups showed that differences were significant regarding age, weight and vascular risk factors (diabetes mellitus, atherosclerosis). Sildenafil was more efficient in the patients of the subgroup IIB. This study suggested that HD was one of many factors causing sexual dysfunction in hemodialysed patients. After this clinical evaluation of sexual dysfunction, we emphasize the value of a global approach of this problem. The use of sildenafil seems to be more valuable in young patients with erectile dysfunction which appeared after long dialysis duration.
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PMID:Sexual dysfunction in male patients undergoing hemodialysis in morocco. 1820 57

Erection is a vascular phenomenon under a psychologic control in a hormonal environment. Erectile dysfunction is defined as the inability to obtain and to maintain sufficient erection for satisfactory intercourse. Organic erectile dysfunction results mainly from vascular problems due to atherosclerosis, a process that begins during childhood, and becomes clinically evident from middle age. Endothelial dysfunction is the first step of atherosclerosis. As the endothelial cells recover the sinusoid spaces in the cavernous tissue and because common risk factors for atherosclerosis have been frequently found in patients with erectile dysfunction, it is logical that vascular impotence presents the same pathophysiology of the other vascular diseases. They share a similar pathogenic involvement of nitric oxide pathway leading to impairment of endothelium dependent vasodilatation and structural vascular abnormalities. Circulating markers of endothelial cell damage have been reported in patients with erectile dysfunction while they have not yet presented any other vascular pathology. Endothelial progenitor cells of bone marrow origin that play a role in promoting endothelial repair are also reduced in vascular abnormalities.As penile arteries have the smallest diameter in the vascular network and because atherosclerosis is a systemic disease, erectile dysfunction could be a sentinel symptom of a more generalized vascular pathology. Modifications of reversible causes or risk factors at the base of the pathogenesis of atherosclerosis remain the first approach toward improving endothelial function and associated with chronic exposure to PDE5-I, they could improve or even cure ED and could avoid fatal cardiovascular attacks in the future.
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PMID:Erectile dysfunction and cardiovascular diseases. 2104 47

We report a case of Tangier disease with Leriche syndrome and bleeding tendency. In this male patient, nasal hemorrhage had been observed frequently throughout childhood. At 46 years old, he experienced effort angina, and coronary angiography demonstrated 75% stenosis in the right coronary artery. Orange-colored tonsils, mild hepatosplenomegaly and very low levels of serum high-density lipoprotein cholesterol (HDL-C) were observed, and the patient was diagnosed with Tangier disease. At 52 years old, effort angina recurred. Coronary angiography revealed 75% stenosis of the left main trunk, left anterior descending, and right coronary arteries. Stenosis of the brachiocephalic and right common iliac arteries was also recorded. Stents were implanted, and coronary artery bypass surgery was performed. At 53 years old, 15 months after surgery, the patient reported intermittent claudication, coldness of feet, and impotence. Aortic angiography showed progression of the stenosis at the bifurcation of the common iliac artery. The patient was diagnosed with Leriche syndrome, and aorta-left external iliac artery graft bypass surgery was performed. After surgery, oozing from subcutaneous tissue and leaking from the anastomotic region were observed. Additional analysis revealed two single-nucleotide polymorphisms (V825I and N935T) in the ATP-binding cassette transporter A1 (ABCA1) gene, and accumulation of small dense low-density lipoprotein together with low levels of HDL-C. In Tangier disease, HDL-C is markedly decreased because of ABCA1 deficiency. However, this is the first reported case to exhibit extensive atherosclerosis and bleeding tendency. This patient had atypical extensive and multiple atherosclerotic lesions, accompanied by Leriche syndrome and uncontrollable bleeding.
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PMID:Accelerated Atherogenicity in Tangier Disease. 2956 93


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