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 the era of highly active antiretroviral therapy, long-term complications of HIV infection and antiretroviral therapy deserve heightened attention. Morphologic and metabolic complications seen during the course of HIV infection encompass a variety of entities that may share a common pathophysiologic pathway. This review article will discuss clinical syndromes such as wasting, lipoatrophy/lipohypertrophy, polymetabolic syndrome as well as hyperlipidemia, cardiovascular disease, lactic acidosis, and metabolic bone disease in HIV-infected patients.
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PMID:Metabolic and morphologic complications of HIV infection. 1708 1

Glycogen storage disease type Ia (GSD Ia) is a rare metabolic disorder due to hepatic glucose-6-phosphatase deficiency. Although great progress has been made in managing affected patients, severe hypoglycemia, lactic acidosis, hyperlipidemia, hepatic cytolysis, and impaired kidney function are frequent. Liver transplantation is the only radical treatment, for which the main indications are hepatic adenomatosis, hepatocellular carcinoma, or severe hepatic dysfunction. We present the case of a patient with end-stage renal disease without focal hepatic lesions and with moderate hepatic metabolic control, and we explain how combined liver-kidney transplantation (LKT) made it possible to correct the metabolic defects responsible for the impaired glucose homeostasis, liberalize the diet, and give birth to a healthy child after an uneventful pregnancy. Patients with end-stage renal disease that resulted from GSD Ia should be considered for LKT even in the absence of hepatic lesions with the aim of improving their quality of life.
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PMID:Combined liver-kidney transplantation in glycogen storage disease Ia: a case beyond the guidelines. 1745 69

Antiretroviral medications have significantly improved the prognosis of subjects infected by human immunodeficiency virus (HIV). However, long-term complications of these drugs are increasingly recognized as significant causes of morbidity and mortality. Non-alcoholic fatty liver disease (NAFLD), which can evolve into non-alcoholic steato-hepatitis (NASH), cirrhosis and ultimately hepatic failure is one of the more often observed complications in the current clinical practice and the correlation with liver enzyme elevations is controversial. Multiple factors have been considered as possibly correlated to this event in the HIV-infected population, including metabolic abnormalities (such as hyperlipidaemia, hyperglycaemia and being overweight), chronic inflammation, concurrent infection with hepatitis C and B viruses, and treatment with certain nucleoside reverse transcriptase inhibitors (NRTI). HIV-associated syndromes such as lactic acidosis and lypodystrophy are frequently associated with fatty liver disease and a mitochondrial injury has been considered as its possible pathogenetic factor. In particular, treatment containing stavudine and didanosine have proven to be the most commonly implicated in the occurrence of mitochondrial abnormalities. Epidemiologic data to better define the role of predictive factors and drugs associated with the development of NAFLD are still lacking. Furthermore, it remains unclear the better therapeutic management for this condition, even if the current best therapeutic option for NAFLD is the treatment of the underlying disease. Other studies are mandatory to better elucidate the pathogenesis of NAFLD and the optimal therapeutic strategy for the underlying conditions.
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PMID:Steatohepatitis in HIV-infected subjects: pathogenesis, clinical impact and implications in clinical management. 1789 69

Paediatric Human Immunodeficiency Virus infection (HIV) nowadays is a chronic disease with an excellent long term prognosis, but lifelong combined antiretroviral treatment is required. However, an improved quality of life in this population is limited by adverse drug effects. The highest risk of treatment toxicity is developing a complete metabolic syndrome including: Hyperlipemia, lipodystrophy, insulin resistance, lactic acidosis, osteopenia, hypertension, and specific system and organ toxicity, such as the kidney, liver, CNS or bone marrow. The risk of cardiovascular disease adult life and also definitive bone mass damage are the most significant metabolic costs that have to paid for increased survival. Most of these toxicities were able to be adequately treated but, pharmacological interferences, patient intolerance and the high number of drugs are the problems that limit the adherence to treatment, which is essential for a good therapeutical efficacy. In this article, we present four HIV paediatric patients who presented with almost the whole range of metabolic toxicities, and a practical overview of therapeutical management.
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PMID:[Antiretroviral drug toxicity in human immunodeficiency virus infected children]. 1844 85

Glycogen storage disease type I (GSD I) is caused by inherited defects of the glucose 6-phosphatase complex, resulting in fasting hypoglycemia, lactic acidosis, hyperuricemia and hyperlipidemia. Sixteen out of 26 (61.5%) GSD I patients in our study had suboptimal levels (<30 ng/ml) of 25-hydroxyvitamin-D (25(OH)D) despite supplementation of vitamin D and/or vitamin D + calcium based on WHO standards in 24/26 (92.3%) patients. The restrictive nature of the GSD I diet, metabolic derangements and intestinal malabsorption seen in GSD I are possible reasons for the observed hypovitaminosis D. Our results suggest that measurement of 25(OH)D should be considered in the routine evaluation of GSD I patients.
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PMID:Hypovitaminosis D in glycogen storage disease type I. 2006 Mar 50

Glycogen storage disease type Ia (GSDIa; von Gierke disease; MIM 232200) is caused by a deficiency in glucose-6-phosphatase-alpha. Patients with GSDIa are unable to maintain glucose homeostasis and suffer from severe hypoglycemia, hepatomegaly, hyperlipidemia, hyperuricemia, and lactic acidosis. The canine model of GSDIa is naturally occurring and recapitulates almost all aspects of the human form of disease. We investigated the potential of recombinant adeno-associated virus (rAAV) vector-based therapy to treat the canine model of GSDIa. After delivery of a therapeutic rAAV2/8 vector to a 1-day-old GSDIa dog, improvement was noted as early as 2 weeks posttreatment. Correction was transient, however, and by 2 months posttreatment the rAAV2/8-treated dog could no longer sustain normal blood glucose levels after 1 hr of fasting. The same animal was then dosed with a therapeutic rAAV2/1 vector delivered via the portal vein. Two months after rAAV2/1 dosing, both blood glucose and lactate levels were normal at 4 hr postfasting. With more prolonged fasting, the dog still maintained near-normal glucose concentrations, but lactate levels were elevated by 9 hr, indicating that partial correction was achieved. Dietary glucose supplementation was discontinued starting 1 month after rAAV2/1 delivery and the dog continues to thrive with minimal laboratory abnormalities at 23 months of age (18 months after rAAV2/1 treatment). These results demonstrate that delivery of rAAV vectors can mediate significant correction of the GSDIa phenotype and that gene transfer may be a promising alternative therapy for this disease and other genetic diseases of the liver.
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PMID:Adeno-associated virus-mediated correction of a canine model of glycogen storage disease type Ia. 2016 45

Patients treated with highly active antiretroviral therapy may develop metabolic side effects such as hyperlipidemia, insulin resistance, lipoatrophy and lactic acidosis. The pathophysiology of these metabolic abnormalities is unknown, although some, e.g., lactic acidosis and lipoatrophy, are more associated with nucleoside use while protease inhibitors (PIs) have been shown to contribute to hyperlipidemia and insulin resistance. Identifying new PIs that are not associated with dyslipidemia has been hindered by the lack of mechanistic information and the unavailability of relevant animal models. In order to understand the molecular mechanism behind the hyperlipidemia associated with other protease inhibitors, and to develop a more effective, faster screen for compounds with this liability, we have analyzed expression profiles from PI-treated animals. Previously, we have shown that treatment of rats with ritonavir results in increases in the expression of proteasomal subunit genes in the liver. We show this increase is similar in rats treated with bortezomib, a proteasome inhibitor. In addition, we have treated rats with additional protease inhibitors, including atazanavir, which is associated with lower rates of lipid elevations in the clinic when administered in the absence of ritonavir. Our results indicate a strong correlation between proteasomal induction and lipid elevations, and have allowed us to develop a rapid screen for identifying novel PIs that do not induce the proteasome.
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PMID:Identification of proteasome gene regulation in a rat model for HIV protease inhibitor-induced hyperlipidemia. 2022 37

Combined antiretroviral therapy has surprisingly improved prognosis of patients infected with human immunodeficiency virus type 1 (HIV-1). Nobel antiretrovirals with potency and activity, dosing convenience, and tolerability have been approved since 1996. However, side effects have been reported with all antiretroviral agents and are the common reasons for switching or discontinuing therapy and for poor adherence. While some frequent adverse effects (e.g., diarrhea, eruption, abnormal dream, jaundice, bone marrow suppression) were reported during clinical trials, some less frequent side effects (e.g., lactic acidosis) and long-term adverse drug reactions (e.g., lipodystrophy, hyperlipidemia) were not identified until the antiretrovirals had been prescribed for years. In this paper, the common adverse effects of major antiretroviral agents, potential preventive measures, and suggested management strategies are described.
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PMID:[Adverse effects of antiretroviral agents, and their treatment]. 2022 94

This anesthetic drug may cause a rare condition named propofol infusion syndrome, characterized by unexplained lactic acidosis, lipemia, rhabdomyolysis, cardiovascular collapse and Brugada-like electrocardiographic pattern or Brugada electrocardiographic phenocopy changes following high-dose propofol infusion over prolonged periods of time. Several articles have contributed to our understanding of the cause of the syndrome, and the growing number of case reports has made it possible to identify several risk factors. Uncertainty remains as to whether a genetic susceptibility exists. The favorable recovery profile associated with propofol offers advantages over traditional anesthetics in clinical situations in which rapid recovery is important. Propofol is a safe anesthetic agent, but propofol infusion syndrome is a rare lethal complication.
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PMID:Propofol infusion syndrome and Brugada syndrome electrocardiographic phenocopy. 2054 10

Family physicians are treating patients infected with human immunodeficiency virus in their practices more often. Long-term complications of this disease are multifactorial and can be related to the virus itself or to adverse effects of antiretroviral therapy. Each drug class has side effects: nucleoside/nucleotide reverse transcriptase inhibitors are associated with lactic acidosis, lipodystrophy, and hyperlipidemia; non-nucleoside reverse transcriptase inhibitors are associated with neuropsychiatric symptoms, rash, liver toxicity, and lipid abnormalities; and protease inhibitors are associated with gastrointestinal intolerance and glucose and lipid abnormalities. The entry inhibitor maraviroc and the integrase inhibitor raltegravir have been approved for treatment-naive and treatment-experienced patients. Maraviroc is associated with bronchitis, nasopharyngitis, and esophageal candidiasis. Adverse effects of raltegravir are comparable to those experienced with placebo, with the exception of increased risk of myopathy and rhabdomyolysis. Information about drug interactions for both of these medications is limited. Non-nucleoside reverse transcriptase inhibitors and protease inhibitors are primarily metabolized through the cytochrome P450 system, and as a result have numerous drug-drug interactions. Monitoring for adverse effects of antiretroviral therapy includes a complete blood count and comprehensive metabolic profile every three to six months. A lipid profile and urinalysis for proteinuria should be per- formed annually. Dual energy x-ray absorptiometry should be considered in patients older than 50 years. Long-term morbidity related to antiretroviral therapy includes liver, renal, glucose, and lipid abnormalities, and cardiovascular and bone disease. With some exceptions for lipid management, these morbidities can be managed as in the general population.
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PMID:Common adverse effects of antiretroviral therapy for HIV disease. 2167 46


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