Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0015695 (fatty liver)
 13,941 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The article reviews the effect of diabetes on the pharmacokinetics and pharmacodynamics of drugs in humans. For most drugs which cross the gastrointestinal wall by passive diffusion, oral absorption is unlikely to be affected by diabetes, although a delay in the absorption of tolazamide and a decrease in the extent of absorption of ampicillin have been reported. Subcutaneous absorption of insulin is more rapid in diabetic patients, whereas the intramuscular absorption of several drugs is slower. The binding of a number of drugs in the blood is reduced in diabetes, which may be due to glycosylation of plasma proteins or displacement by plasma free fatty acids, the level of which is increased in diabetic patients. Plasma concentrations of albumin and alpha 1-acid glycoprotein do not appear to be changed by the disease. The distribution of drugs with little or no binding in the blood is generally not altered, although the volume of distribution of phenazone (antipyrine) is reduced by 20% in insulin-dependent diabetes mellitus (IDDM). In contrast to animal studies, the metabolic clearance of most drugs in humans appears to be unaffected or slightly reduced by the disease. The presence of fatty liver in non-insulin-dependent diabetes mellitus (NIDDM) may contribute to a reduced hepatic clearance, whereas decreased binding in the blood may cause an increase in clearance. The effect of diabetes on hepatic blood flow in humans appears to be unknown. Diabetes affects kidney function in a significant number of diabetic patients. During the first 10 years after the onset of the disease, glomerular filtration is elevated in these patients. Thus, the renal clearance of a number of antibiotics has been shown to be increased in diabetic children. As the disease progresses, renal function is impaired and glomerular function declines from the initial elevated state. In diabetic adults the renal clearance of drugs either is comparable with that found in nondiabetic individuals or is reduced. A limited number of studies have been conducted comparing the dose-response of cardiovascular drugs in diabetic patients with that in nondiabetic controls. Decreased, increased and unchanged responses have been reported. It is apparent that in some cases an altered response may be observed for a drug when administered to a diabetic patient compared with a similar nondiabetic individual. At the present time, it is not possible to ascertain whether these studies reflect true pharmacodynamic changes or merely alterations in pharmacokinetics.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:The effects of diabetes mellitus on pharmacokinetics and pharmacodynamics in humans. 204 31

Polychlorinated biphenyls (PCBs) exposure is closely associated with the prevalence of metabolic diseases, including fatty liver and dyslipidemia. Emerging literature suggests that disturbance of gut microbiota is related to PCB126-induced metabolic disorders. However, the causal role of dysbiosis in PCB126-induced fatty liver is still unknown. To clarify the role of the gut microbiome in the detoxification of PCB126 in intestine or PCB126-induced toxicity in liver, mice were administrated with drinking water containing antibiotics (ampicillin, vancomycin, neomycin, and metronidazole) or Inulin. We showed that PCB126 resulted in significant hepatic lipid accumulation, inflammation, and fibrosis. PCB126, Antibiotics, and Inulin significantly affected the structure and shifted community membership of gut microbiome. 7 KEGG (Kyoto Encyclopedia of Genes and Genomes) pathways at level 2 and 39 KEGG pathways at level 3 were significantly affected. Antibiotics alleviated PCB126-induced fibrosis in the liver but increased inflammation. Inulin treatment ameliorated both inflammation and fibrosis in the liver of PCB126-treated mice. Neither Antibiotics nor Inulin had significant effect on PCB126-induced hepatic steatosis. The more specific intervention of gut microbiota is needed to alleviate PCB126-induced fatty liver. These data demonstrate that homeostasis of gut microbiota is critical for the defense against PCB126 toxicity and dysbiosis plays a fundamental role in the development of inflammation and fibrosis in liver of PCB126-treated mice.
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PMID:Homeostasis of gut microbiota protects against polychlorinated biphenyl 126-induced metabolic dysfunction in liver of mice. 3214 51