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)

Proteins are particularly attractive targets for product analysis, which is used to understand pathology. Protein modifications, such as advanced glycation end products (AGEs), serve as footprints of biochemical processes and also help in the search for novel agents that efficiently inhibit protein damage. Interestingly, several medical agents that are used clinically interfere with oxidative protein damage through different mechanisms characteristic of their chemical structures. We recently found that angiotensin II receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) lower the in vitro formation of the AGEs pentosidine and carboxymethyllysine. Their inhibition for AGE formation is more striking than aminoguanidine. Unlike aminoguanidine, ARBs and ACEIs do not trap reactive carbonyl precursors of AGEs. Rather, they inhibit AGE formation, possibly as a result of their potent ability to scavenge hydroxyl radicals and to chelate the transition metals necessary for the Fenton reaction. We tested their AGE-lowering ability in vivo in a unique type-2 diabetic model with nephropathic SHR/NDmcr-cp rats, which exhibits the metabolic syndrome (obesity, hyperglycemia, hyperlipidemia, hyperinsulinemia) in addition to hypertension. Obesity and associated metabolic derangements, in addition to hypertension, markedly accelerate renal injury. Expectedly, correction of hyperglycemia and hyperinsulinemia partially but significantly improves renal injury. A low-calorie diet greatly improves renal injury despite persistent hypertension. Among antihypertensive agents, ARBs, unlike nifedipine and atenolol, are renoprotective despite persistent metabolic syndrome, but their action is independent of blood pressure lowering and is observed in a dose-dependent manner despite the complete blockade of angiotensin II receptor. Interestingly, the improvement of renal injury by ARBs as well as a low-calorie diet is associated with a significant reduction in local oxidative stress and AGE formation in the kidney. During the characterization of the AGE-lowering profile of our chemical compound libraries ( approximately 2000), we identified several inhibitors of oxidative stress and advanced glycation. They are indeed renoprotective, independently of correction of hypertension and metabolic syndrome, in experimental diabetic nephropathy and other nephritis models. Altogether, our data are in good agreement with the recent therapeutic concept for diabetic nephropathy that multiple risk factor interventions are critical in the treatment of diabetic renal injury, and further implicate a therapeutic potential of inhibition of oxidative stress and advanced glycation.
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PMID:From molecular footprints of disease to new therapeutic interventions in diabetic nephropathy. 1603 1

Immune nephritis in rats was induced by administration of nephrotoxic rabbit antiserum. The development of severe renal inflammation (proteinuria, edema, lipemia, increased erythrocyte sedimentation rate, and 30% mortality) was accompanied by hypercoagulation and inhibition of fibrinolysis. Repeated subcutaneous injections of thymoptin in a low dose of 0.1 microg/200 g (5 injections every other day) increased the severity of inflammation and prethrombotic state of the blood. Lengthening the period between injections (5 injections at 5-day intervals) was followed by a tendency toward attenuation of nephritis and correction of hypercoagulation. In healthy rats, thymoptin produced an opposite effect on hemostasis, which was manifested in moderate stimulation of fibrinolysis and hypocoagulation.
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PMID:Effect of thymoptin on hemostasis and fibrinolysis in rats with experimental nephritis. 1914 36

Mesangial lupus nephritis (type II according to the WHO classification) is usually considered a benign variant. Its clinical manifestations are minimal: hematuria and proteinuria, normal sediment, and normal renal function. To evaluate the clinical manifestations and course in mesangial nephritis, we studied 20 patients with a histological diagnosis of type II lupus nephritis who attended our clinic. We found that clinical presentation was atypical in a significant proportion of these patients. Data from the two groups of patients were compared: those with classical presentation and those with atypical presentation. The results were analyzed with descriptive and inferential statistics. Twenty patients (19 women and 1 man) were included. The mean age at nephritis onset was 33.9 years and the mean length of follow-up was 4.2 years. Clinical presentation was atypical in 17 patients, with active urinary sediment in 12, urine protein>1 g/24 h in 7, and reduction in creatinine clearance in 14. Clinical remission was achieved with treatment in 16 patients, with subsequent flares in 8. All flares responded well to treatment. Biopsies in 5 patients with flares showed progression to type III and IV nephritis. At the end of the follow-up period, 4 patients had chronic renal failure. Some of our patients with mesangial lupus nephritis did not have the benign course that is usually described. Despite a good initial response, 20% of the patients progressed to chronic renal failure. Initial hyperlipidemia and proteinuria seem to correlate with a more aggressive course.
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PMID:[Atypical presentation and clinical course in mesangial lupus nephritis]. 2179 95

Systemic lupus erythematosus (SLE) predominantly affects women in their reproductive years. Renal disease (glomerulonephritis) is one of the most frequent and serious manifestations of SLE. Of the various histological types of lupus glomerulonephritis, diffuse proliferative nephritis carries the worst prognosis. Combined with high-dose prednisone, mycophenolate mofetil (MMF) has emerged as a first-line immunosuppressive treatment, although data regarding the efficacy of MMF on the long-term preservation of renal function are forthcoming. Cyclophosphamide is reserved for more severe forms of lupus nephritis, such as crescentic glomerulonephritis with rapidly deteriorating renal function, patients with significant renal function impairment at presentation, and refractory renal disease. Evidence for the calcineurin inhibitors in the treatment of lupus nephritis is weaker, and it concerns patients who are intolerant or recalcitrant to other agents. While further controlled trials are mandatory, B cell modulation therapies, such as rituximab, belimumab and epratuzumab are confined to refractory disease. Non-immunosuppressive measures, such as angiotensin-converting enzyme inhibitors, vigorous blood pressure control, prevention and treatment of hyperlipidemia and osteoporosis, are equally important.
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PMID:Understanding lupus nephritis: diagnosis, management, and treatment options. 2267 66

Ganoderma lucidum (Lingzhi or Reishi) is known as a bitter mushroom with remarkable health benefits. The active constituents found in mushrooms include polysaccharides, dietary fibers, oligosaccharides, triterpenoids, peptides and proteins, alcohols and phenols, mineral elements (such as zinc, copper, iodine, selenium, and iron), vitamins, and amino acids. The bioactive components found in the G. lucidum mushroom have numerous health properties to treat diseased conditions such as hepatopathy, chronic hepatitis, nephritis, hypertension, hyperlipemia, arthritis, neurasthenia, insomnia, bronchitis, asthma, gastric ulcers, atherosclerosis, leukopenia, diabetes, anorexia, and cancer. In spite of the voluminous literature available, G. lucidum is used mostly as an immune enhancer and a health supplement, not therapeutically. This review discusses the therapeutic potential of G. luidum to attract the scientific community to consider its therapeutic application where it can be worth pursuing.
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PMID:Probing Lingzhi or Reishi medicinal mushroom Ganoderma lucidum (higher Basidiomycetes): a bitter mushroom with amazing health benefits. 2355 65

As a major factor participating in the organism antioxidation and detoxification process, GSH is of vital importance to human beings. Detecting GSH content in single cells is significant to diagnosis and prevention of many diseases. In this work, the amount of GSH within single erythrocytes was detected and analyzed via statistical analysis. All erythrocytes tested were collected from people in different ages and people of different pathological states. The correlation between GSH level, age and pathological state were investigated. Results showed that the GSH level in erythrocytes decreased with the ages of patients increased. There was little difference between the GSH level in erythrocytes from people who had chronic diseases (hyperglycemia, hyperlipidemia and hypertension) and from healthy people. However, the GSH level in erythrocytes from people who had inflammation (myocarditis, nephritis and gastritis) was generally higher than that from the healthy people. This study provides basic data for researches of cell senescence and cytopathic effect and is helpful to diagnosis and prevention of diseases. In addition, it also provides a simple and effective method for rapid GSH detection within single cell.
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PMID:Detection of glutathione within single erythrocyte of different ages and pathological state using microfluidic chips coupled with laser induced fluorescence. 2598 61

Hyperlipidaemia accompanies chronic renal disease either as a consequence of the renal dysfunction or as part of generalized metabolic derangements. Under both situations, the lipid profile is characterized by accumulation of triglyceride-rich lipoproteins (TGRLs). This lipid profile is recognized as a risk factor for cardiovascular complications. Whether it may pose a risk for renal injury as well remains unclear. A hyper-TGRL state was generated in C57BL/6 mice using poloxamer-407 (P-407) and immune complex-mediated renal injury was triggered using the accelerated nephrotoxic nephritis (ANTN) model. The hyper-TGRL animals were hypersensitive to ANTN demonstrated by greater haematuria and glomerular cellularity. These changes were accompanied by increased glomerular accumulation of CD68+ macrophages. The hypersensitive response to ANTN was not seen in low-density lipoprotein receptor knock-out mice fed with a high fat diet, where triglyceride levels were lower but cholesterol levels comparable to those obtained using P-407. These data indicate that a hyper-TGRL state might be more detrimental to the kidneys than low-density lipoprotein-driven hypercholesterolaemia during immune complex-mediated nephritis. We speculate that the hyper-TGRL environment primes the kidney to exacerbated renal damage following an inflammatory insult with increased accumulation of macrophages that may play a key role in mediating the injurious effects.
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PMID:A triglyceride-rich lipoprotein environment exacerbates renal injury in the accelerated nephrotoxic nephritis model. 2940 70

Alport syndrome (AS) is a rare genetic disorder that causes progressive nephritis and is more common among males. Studies have reported an association between thyroid antibodies and hypothyroidism in patients with AS, but the relevance of this relationship is under debate. Prolonged untreated hypothyroidism induces short stature, abnormal pubertal development, and various other symptoms. However, children with long-standing hypothyroidism rarely present with signs of precocious puberty, or Van Wyk-Grumbach syndrome (VWGS). We report the case of a boy, 8 years and 4 months old, who had VWGS caused by prolonged untreated congenital hypothyroidism and AS. The boy had repeated gross hematuria and proteinuria and was diagnosed with AS by renal biopsy and genetic testing. He had normal renal function but severe growth retardation and hypothyroidism. Obesity, bone age delay, hyperlipidemia, and abnormal increased testicle size were also present due to prolonged untreated hypothyroidism. His thyroid antibody titer elevation was unclear, although ultrasonography and thyroid scanning showed a decrease in thyroid volume. We diagnosed the patient with congenital hypothyroidism caused by thyroid dysgenesis. VWGS was diagnosed due to hypothyroidism, delayed bone age, and pseudoprecocious puberty. To the best of our knowledge, this is the first report of a prepubertal Korean boy with prolonged untreated congenital hypothyroidism complicated by VWGS in AS.
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PMID:An Alport syndrome boy with Van Wyk-Grumbach syndrome induced by prolonged untreated congenital hypothyroidism. 3261 94


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