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)

The influences of endogenous factors (sex, age, premorbid personality traits, heredity) and exogenous factors (somatogenias, cranial injuries and neuroinfections, intoxications, psychogenias) on the origin and course of psychotic syndromes and dementia were regarded on the basis of clinical and epidemiological studies carried out in 523 patients with cerebral atherosclerosis. The leading risk factors were established for each form of mental disorders due to cerebral atherosclerosis.
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PMID:[The correlation of endogenous and exogenous factors in the occurrence and course of mental disorders in cerebral atherosclerosis]. 133 41

This review expands information concerning the bilateral below-knee (BK) amputee, describing the findings of a retrospective assessment of 80 such patients. Factors evaluated included etiology, associated conditions, time between amputations, late revisions, use of prostheses, and survival. In 63 patients both amputations were because of atherosclerosis. Of these patients, 86% were diabetic and 84% hypertensive. Peak incidence of the second amputation was during the 7th decade. Average time between amputations was 23 months. Forty-five (71%) of the atherosclerotic patients achieved some functional use of bilateral prostheses. The five patients employed at the time of the second amputation returned to work using prostheses. Average survival after the second amputation was 44 months for those deceased, and 64 months for those alive at the end of the study period. Nine patients had amputations because of various forms of injury, including one for sequential developments due to alcohol-related sensory loss. Eight of this group had a diagnosis of alcohol abuse of psychosis. Reasons for amputations included frostbite, burns, suicide attempt and sensory loss. Five achieved long-term but generally suboptimal prostheses use. The findings support the impression that most atherosclerotic bilateral BK amputees can use prostheses and that their survival and low rate of late stump revisions justify restorative efforts. Mental status was the major determinant of amputation and prostheses use among the non-atherosclerotic patients; discharge from psychiatric hospitals without adequate community support systems was probably contributory. Management and prevention require close collaboration between the rehabilitation, surgical, psychosocial, and public health disciplines.
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PMID:Bilateral below-knee amputations: experience with 80 patients. 395 77

Results of clinico-morphological and biochemical examinations of 66 autopsy cases are presented. At lifetime the deceased were suffering from atherosclerosis: 16 of them showed no psychotic disturbances; 14 had a pseudoparalytic, 20 a lacunar, and 14 a senile-like form of dementia. With the use of histological staining 22 brain specimens were examined. The biochemical examinations included determinations of total cholesterol, cholesterol fractions, total lipid phosphorus, lecithine, sphingomyelin, phosphatidyl-ethanolamine and diphosphoinositide. It has been found that the process of brain atrophy has a certain relation to the psychotic symptoms and shows a progress from the first to the last group. Qualitative and quantitative changes of lipids are manifest. The content of phospholipids, and, first of all, lecithine, drops, the content of total cholesterol rises, and bound cholesterol appears. Atherosclerosis is a disease at the basis of which there are persistent disturbances of lipid metabolism and biosynthesis of brain lipids.
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PMID:[Pathohistologic and biochemical changes in the brain in atherosclerosis and atherosclerotic dementia]. 741 33

Atherosclerosis is manifested as coronary artery disease (CAD), ischemic stroke and peripheral vascular disease. Moderate alcohol consumption has been associated with reduction of CAD complications. Apparently, red wine offers more benefits than any other kind of drinks, probably due to flavonoids. Alcohol alters lipoproteins and the coagulation system. The flavonoids induce vascular relaxation by mechanisms that are both dependent and independent of nitric oxide, inhibits many of the cellular reactions associated with atherosclerosis and inflammation, such as endothelial expression of vascular adhesion molecules and release of cytokines from polymorphonuclear leukocytes. Hypertension is also influenced by the alcohol intake. Thus, heavy alcohol intake is almost always associated with systemic hypertension, and hence shall be avoided. In individuals that ingest excess alcohol, there is higher risk of coronary occlusion, arrhythmias, hepatic cirrhosis, upper gastrointestinal cancers, fetal alcohol syndrome, murders, sex crimes, traffic and industrial accidents, robberies, and psychosis. Alcohol is no treatment for atherosclerosis; but it doesn't need to be prohibited for everyone. Thus moderate amounts of alcohol (1-2 drinks/day), especially red wine, may be allowed for those at risk for atherosclerosis complications.
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PMID:Alcohol and atherosclerosis. 1124 69

Platelet activation is involved in the pathogenesis of atherosclerosis and venous thromboembolism, and might therefore be a possible link between the two entities. Prolactin and leptin have recently been recognized as potent co-activators of ADP-dependent platelet aggregation or P-selectin expression, and are therefore suspected as additional risk factors for both arterial and venous thrombosis. There are clinical situations that have a known association with higher prolactin or leptin levels (pregnancy, obesity or anti-psychotic therapy) and increased risk of thromboembolic events. We compared the impact of both hormones on platelet activation in vitro and in vivo, indicating that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. We have also demonstrated that prolactin levels are increased in so called idiopathic thrombosis, and that conversely, patients with prolactinoma have an increased frequency of thrombosis during the hyperprolactinemic state, in a retrospective analysis. Moreover, we have demonstrated increased prolactin values in stroke and myocardial infarction. Prospective studies have yet to be performed to give this theory its final confirmation. The involvement of hormonal factors in platelet aggregation and venous or arterial thrombosis may have important clinical implications such as for risk stratification of patients with venous and arterial thrombosis or new therapeutic options such as decreasing pro-coagulant hormone levels in certain risk situations.
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PMID:Co-activation of platelets by prolactin or leptin--pathophysiological findings and clinical implications. 1498 99

Androgenic-anabolic steroids (AAS) are synthetic derivatives of the male hormone testosterone. They can exert strong effects on the human body that may be beneficial for athletic performance. A review of the literature revealed that most laboratory studies did not investigate the actual doses of AAS currently abused in the field. Therefore, those studies may not reflect the actual (adverse) effects of steroids. The available scientific literature describes that short-term administration of these drugs by athletes can increase strength and bodyweight. Strength gains of about 5-20% of the initial strength and increments of 2-5 kg bodyweight, that may be attributed to an increase of the lean body mass, have been observed. A reduction of fat mass does not seem to occur. Although AAS administration may affect erythropoiesis and blood haemoglobin concentrations, no effect on endurance performance was observed. Little data about the effects of AAS on metabolic responses during exercise training and recovery are available and, therefore, do not allow firm conclusions. The main untoward effects of short- and long-term AAS abuse that male athletes most often self-report are an increase in sexual drive, the occurrence of acne vulgaris, increased body hair and increment of aggressive behaviour. AAS administration will disturb the regular endogenous production of testosterone and gonadotrophins that may persist for months after drug withdrawal. Cardiovascular risk factors may undergo deleterious alterations, including elevation of blood pressure and depression of serum high-density lipoprotein (HDL)-, HDL2- and HDL3-cholesterol levels. In echocardiographic studies in male athletes, AAS did not seem to affect cardiac structure and function, although in animal studies these drugs have been observed to exert hazardous effects on heart structure and function. In studies of athletes, AAS were not found to damage the liver. Psyche and behaviour seem to be strongly affected by AAS. Generally, AAS seem to induce increments of aggression and hostility. Mood disturbances (e.g. depression, [hypo-]mania, psychotic features) are likely to be dose and drug dependent. AAS dependence or withdrawal effects (such as depression) seem to occur only in a small number of AAS users. Dissatisfaction with the body and low self-esteem may lead to the so-called 'reverse anorexia syndrome' that predisposes to the start of AAS use. Many other adverse effects have been associated with AAS misuse, including disturbance of endocrine and immune function, alterations of sebaceous system and skin, changes of haemostatic system and urogenital tract. One has to keep in mind that the scientific data may underestimate the actual untoward effects because of the relatively low doses administered in those studies, since they do not approximate doses used by illicit steroid users. The mechanism of action of AAS may differ between compounds because of variations in the steroid molecule and affinity to androgen receptors. Several pathways of action have been recognised. The enzyme 5-alpha-reductase seems to play an important role by converting AAS into dihydrotestosterone (androstanolone) that acts in the cell nucleus of target organs, such as male accessory glands, skin and prostate. Other mechanisms comprises mediation by the enzyme aromatase that converts AAS in female sex hormones (estradiol and estrone), antagonistic action to estrogens and a competitive antagonism to the glucocorticoid receptors. Furthermore, AAS stimulate erythropoietin synthesis and red cell production as well as bone formation but counteract bone breakdown. The effects on the cardiovascular system are proposed to be mediated by the occurrence of AAS-induced atherosclerosis (due to unfavourable influence on serum lipids and lipoproteins), thrombosis, vasospasm or direct injury to vessel walls, or may be ascribed to a combination of the different mechanisms. AAS-induced increment of muscle tissue can be attributed to hypertrophy and the formation of new muscle fibres, in which key roles are played by satellite cell number and ultrastructure, androgen receptors and myonuclei.
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PMID:Effects of androgenic-anabolic steroids in athletes. 1524 88

Hormones such as prolactin and leptin have recently been recognized as potent platelet aggregation co-activators, and have therefore been postulated as an additional risk factor for both arterial and venous thrombosis. Clinical situations exist that are known to be associated with higher leptin and/or prolactin levels (obesity, pregnancy, prolactinomas and anti-psychotic therapy respectively) and increased venous thrombosis or atherosclerosis risk. Therefore, we compared the impact of both hormones on platelet activation in vitro and in vivo. First, we investigated platelet aggregation and P-selectin expression after stimulation with 1,000 mU/l prolactin or 100 ng/ml leptin in five healthy volunteers in vitro. Prolactin revealed significant higher levels of P-selectin expression and platelet aggregation than leptin in all subjects. We also compared the correlation of prolactin and leptin values with the P-selection expression on platelets. Previously, we detected a significant correlation between prolactin values and ADP-stimulated P-selectin expression on platelets in pregnant women, patients with pituitary tumours, and patients on anti-psychotic therapy. In contrast, leptin did not correlate with P-selectin expression in all subject groups investigated. However, leptin correlated with body mass index in the subjects investigated. Our data indicate that prolactin has a stronger effect on platelet activation as leptin in vitro and in vivo. Moreover, our data suggest that the stronger effect of prolactin on ADP-stimulated platelet aggregation, compared to leptin, depends on higher stimulation of CD62p expression by prolactin.
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PMID:Differences in platelet activation by prolactin and leptin. 1530 27

In order to clarify the role of the central nervous system in the genesis of arterial hypertension (AH) a population analysis of somatic pathology in schizophrenia was performed. Using clinical and postmortem data, the study found lower frequency of AH among mental patients vs. somatic ones; primary AH was benign independently of the psychotropic therapy regimen. II to III stage AH in psychosis was associated with primary or secondary renal pathology or magistral vessel atherosclerosis. Severe schizophrenia and a pronounced personality defect were associated with low intensity of the primary form of somatic nosology.
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PMID:[Population models in the study of the neurogenic determinants of arterial hypertension. Report I. Peculiarities of arterial hypertension in schizophrenia]. 1821 52

Endoplasmic reticulum (ER) stress is involved in a wide range of pathological circumstances including neurodegenerative disorders, diabetes mellitus, ischemic injury, cancers, atherosclerosis, inflammation, infection, toxicity of chemicals and metals, and psychotic diseases. ER stress is also involved in some physiological events including development of particular cell types. A number of pathophysiological triggers cause accumulation of unfolded proteins in the ER, i.e., ER stress. In response to accumulation of unfolded/misfolded proteins, cells adapt themselves to the stress conditions via a coordinated adaptive program, the unfolded protein response (UPR). UPR is a double-edged sword. It induces both prosurvival and proapoptotic signaling. It also triggers both proinflammatory and anti-inflammatory signals. In this review, I summarize current knowledge on putative, pathophysiological roles of ER stress in the kidney.
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PMID:Endoplasmic reticulum stress in the kidney. 1853 67

The complexity and flexibility of cellular architectures is increasingly recognized by impressive progress on the side of molecular analytics, i.e. proteomics, genomics and metabolomics. One of the messages from systems biology is that the number of molecular species in cellular networks is orders of magnitude bigger than anticipated by genomic analysis, in particular by fast posttranslational modifications of proteins. The requirements to manage external signals, integrate spatiotemporal signal transduction inside an organism and at the same time optimizing networks of biochemical and chemical reactions result in chemically extremely fine tuned molecular entities. Chemical side reactions of enzymatic activity, like e.g. random oxidative damage of proteins by free radicals during aging constantly introduce epigenetic alterations of protein targets. These events gradually and on an individual stochastic scale, keep modifying activities of these targets, and their affinities and selectivities towards biological and pharmacological ligands. One further message is that many of the key reactions in living systems are essentially based on interactions of low affinities and even low selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. So, in complex disorders like cancer or neurodegenerative diseases, which are rooted in relatively subtle and multimodal dysfunction of important physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which still dominate the pharmaceutical industry increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade and the treatment of "complex diseases" remains a most pressing medical need. Currently a change of paradigm can be observed with regard to a new focus on agents that modulate multiple targets simultaneously. Targeting cellular function as a system rather than on the level of the single protein molecule significantly increases the size of the drugable proteome and is expected to introduce novel classes of multi-target drugs with fewer adverse effects and toxicity. Multiple target approaches have recently been used to design medications against atherosclerosis, cancer, depression, psychosis and neurodegenerative diseases. A focussed approach towards "systemic" drugs will certainly require the development of novel computational and mathematical concepts for appropriate modelling of complex data and extraction of "screenable" information from biological systems essentially ruled by deterministic chaotic processes on a background of individual stochasticity.
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PMID:What does systems biology mean for drug development? 1853 27


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