PURPOSE: Several studies have suggested that hyperlipidemia might be a causative factor contributing to the progression of initial glomerular injury through the development of glomerulosclerosis. We examined the potential beneficial effect of atorvastatin - which blocks the rate limiting step of cholesterol synthesis by inhibiting HMG-CoA reductase - in PAN- induced nephrosis. MATERIALS AND METHODS: Glomerulosclerosis was induced in Sprague-Dawley male rats by repeated administration of PAN. Sprague-Dawley male rats were divided into 3 groups:group I(control), group II(PAN 20 mg/kg, subcutaneous injection), group III(PAN 20 mg/kg subcutaneous injection and atorvastatin 50 mg/kg/day per oral). On the 11th week, upon sacrifice of the experimental animals, blood sampling, 24-hr urine collection and nephrectomy were performed. RESULTS: Group III had significantly lower BUN and higher serum albumin(30.9+/-17.2 vs. 17.3+/-2.5 mg/dL; 2.3+/-0.1 vs. 2.5+/-0.2 g/dL, P<0.05) compared with group II. In the lipid profiles, group III was associated with a reduction in total cholesterol and LDL(291+/-173 vs. 167+/-72 mg/dL; 57+/-53 vs. 27+/-12 mg/dL, P>0.05) compared with group II. Atorvastatin administration lowered the glomerular sclerosing index significantly(26.2% vs. 13.3%, P<0.05). CONCLUSION: Puromycin-induced glomerulosclerosis could be ameliorated by the reduction of hyperlipidemia with atorvastatin. This suggests that hyperlipidemia contributes to the pathogenesis of glomerulosclerosis.
Animals ; Cholesterol ; Humans ; Hyperlipidemias ; Injections, Subcutaneous ; Male ; Nephrectomy ; Nephrosis* ; Oxidoreductases ; Puromycin* ; Rats* ; Rats, Sprague-Dawley ; Urine Specimen Collection

Maple syrup urine disease is an autosomal recessive disease caused by a deficiency of the branched-chain alpa-ketoacid dehydrogenase complex. The disease is often suspected because of the peculiar odor of maple syrup in urine. Maple syrup urine disease is usually confirmed by amino acid analysis and urine organic acid analysis showing marked elevations of leucine, isoleucine, valine, and respective ketoacids in blood and urine. We experienced a case of a newborn patient with maple syrup urine disease, who suffered from poor feeding, irritability, hypotonicity and generalized convulsions. She was promptly treated with peritoneal dialysis and branched-chain amino acid free diet. The patient was controlled successfully and discharged.
Acer* ; Diet* ; Humans ; Infant, Newborn ; Isoleucine ; Leucine ; Maple Syrup Urine Disease* ; Odors ; Oxidoreductases ; Peritoneal Dialysis* ; Seizures ; Valine

Maple syrup urine disease (MSUD) is an autosomal recessive disease caused by a deficiency in subunits of the branched-chain alpha-ketoacid dehydrogenase complex (BCKDH). The disease is characterized by the accumulation of the branched-chain amino acids leucine, isoleucine, valine, alloisoleucine, and their corresponding alpha-ketoacid in blood and urine. MSUD is a heterogenous disorder, and classic, intermittent, intermediate and thiamine-responsive phenotypes have been identified. We experienced a case of Maple syrup urine disease (classic type) in a female neonate, who suffered from lethargy, poor feeding, apnea, alternating periods of hypertonicity and flaccidity, generalized convulsions, and a peculiar burned sugar smell from the body and urine. She died of respiratory failure 22 days after the birth. The brief review of the literature was made.
Acer* ; Amino Acids, Branched-Chain ; Apnea ; Burns ; Female ; Humans ; Infant, Newborn ; Isoleucine ; Lethargy ; Leucine ; Maple Syrup Urine Disease* ; Oxidoreductases ; Parturition ; Phenotype ; Respiratory Insufficiency ; Seizures ; Smell ; Valine

CYP1A2, CYP2D6 and N-acetyltransferase activities were estimated in 100 patients with bladder cancer and 84 control subjects from measurements of theophylline, metoprolol and isoniazid and their metabolites in urine, respectively. The frequency of occurrence of slow acetylators of isoniazid and poor metabolizers of metoprolol were 16.7% and 1.2% in the control group and 16.3% and 2.0% in the cancer patient group. These differences were not significant. The recovery ratio of 1-methyluric acid(1-MU) from theophylline was significantly higher in patients with bladder cancer than in control subjects(0.340 +/- 0.016 versus 0.260 +/- 0.020, p< 0.05). The 1-MU recovery ratio was a significant, independent risk factor among the metabolic capacities tested as shown by logistic regression analysis, controlling for N-acetylation of isoniazid, hydroxylation of metoprolol, age, sex, and smoking. We concluded that the capacity for 3-demethylation of theophylline, as a reflection of CYP1A2 activity, is significantly associated with increased risk of nonoccupational urinary bladder cancer.
Acetylation ; Adult ; Aged ; Amines/metabolism ; Bladder Neoplasms/enzymology/*epidemiology ; Carcinoma, Transitional Cell/enzymology/*epidemiology ; Case-Control Studies ; Cytochrome P-450 CYP1A2 ; Cytochrome P-450 CYP2D6 ; Cytochrome P-450 Enzyme System/metabolism/*urine ; Disease Susceptibility ; Enzyme Induction ; Female ; Human ; Isoniazid/*pharmacokinetics ; Korea/epidemiology ; Logistic Models ; Male ; Methylation ; Metoprolol/*pharmacokinetics ; Middle Age ; Mixed Function Oxygenases/metabolism ; Mixed Function Oxygenases/metabolism ; Oxidoreductases/*urine ; Smoking ; Support, Non-U.S. Gov't ; Theophylline/*pharmacokinetics ; Uric Acid/analogs & derivatives/urine

OBJECTIVETo evaluate the influence of individual genetic polymorphisms of metabolic enzymes on urinary styrene metabolites.

METHODS58 workers occupationally exposed to styrene were divided into the high exposure group (≥ 100 mg/m³) and the low exposure group (< 100 mg/m³). The microfluidic chip technology was used to determine the SNPs of CYP2B6, CYP2D6 and GSTP1 and the influence of gene polymorphisms on the metabolism of styrene was statistically analyzed.

RESULTSThe level of urine styrene metabolites level was influenced by genotypes of CYP2B6, CYP2D6 and GSTP1 [(280.28 +/- 100.60) mg/g Cr vs (183.48 +/- 127.52) mg/g Cr, (233.04 +/- 77.56) mg/g Cr vs (152.46 +/- 95.47) mg/g Cr, (32.88 +/- 7.14) mg/g Cr vs (24.47 +/- 5.59) mg/g Cr, P < 0.05)]. The metabolism of CYP2B6 G/G homozygotic genotype to styrene was more active than G/T heterozygotic genotype and T/T mutation genotype. The level of PHEMA in GSTP1 homozygotic genotype subjects was significantly higher than that in the group of homozygotic genotype [(32.07 +/- 7.32) mg/g Cr vs (25.59 +/- 6.95) mg/g Cr, P < 0.05)]. The influence of CYP2D6 genotypes on urinary metabolites was also observed in the same study [(56.36 +/- 109.72) mg/g Cr vs (177.13 +/- 116.21) mg/g Cr, (118.73 +/- 84.55) mg/g Cr vs (148.48 +/- 99.83) mg/g Cr, (18.29 +/- 13.50) mg/g Cr vs (19.95 +/- 13.30) mg/g Cr, P < 0.05)].

CONCLUSIONGenotypes of CYP2B6, GSTP1 and CYP2D6 are related to susceptibility to the metabolism of styrene in human.

Adult ; Aryl Hydrocarbon Hydroxylases ; genetics ; Cytochrome P-450 CYP2B6 ; Cytochrome P-450 CYP2D6 ; genetics ; Genotype ; Glutathione S-Transferase pi ; genetics ; Humans ; Male ; Middle Aged ; Occupational Exposure ; adverse effects ; Oxidoreductases, N-Demethylating ; genetics ; Polymorphism, Genetic ; Styrene ; adverse effects ; pharmacokinetics ; urine ; Young Adult