Respiratory failure is one of the major causes of death in patients with paraquat poisoning. In paraquat-poisoned lungs, abnormal extracellular matrix regulation occurs. The aim of the present study is to determine whether serum concentrations of type IV collagen and tissue inhibitor of metalloproteinase-1 (TIMP-1) are altered during the course of paraquat poisoning and whether haemoperfusion therapy affects these concentrations. Twenty-one patients were admitted within 3 h after ingestion of paraquat and all patients received direct haemoperfusion therapy. Five out of 21 patients survived and 16 patients died within 28 days. Plasma paraquat concentrations in non-survivors (5740 +/- 380 microg l(-1)) were not significantly different from those in survivors ( 5920 +/- 280 microg l(-1)) before treatment. Haemoperfusion reduced these concentrations in both non-survivors (120 +/- 7 microg l(-1)) as well as survivors (136 +/- 9 microg l(-1)) on day 5. Serum concentrations of type IV collagen and TIMP-1 in survivors showed little change between day 1 (type IV collagen, 90.4 +/- 3.6 ng ml(-1); TIMP-1, 172.2 +/- 7.0 ng ml(-1)) and day 5 (type IV collagen, 92.6 +/- 4.2 ng ml(-1); TIMP-1, 174.2 +/- 7.2 ng ml(-1)). In contrast, these concentrations in non-survivors on day 5 (type IV collagen, 143.6 +/- 7.8 mg ml(-1); TIMP-1, 246.8 +/- 13.6 ng ml(-1)) were significantly higher than those on day 1 (type IV collagen, 88.4 +/- 4.2 ng ml(-1), P < 0.01; TIMP-1, 170.6 +/- 9.2 ng ml(-1), P < 0.05). These data suggest that serum concentrations of type IV collagen and TIMP-1 may be useful indicators for the development of respiratory failure in patients with paraquat poisoning.

Adult↗

PubMedDate not supplied

Biochemical and morphological study of cardiac hypertrophy. Effects of thyroxine on enzyme activities in the rat myocardium.

Experimental hyperthyroidism induced in rats by daily injections of 3,3',5,5'-tetraiode-L-thyroxine (0.5 mg/kg i.p.) for 14 days resulted in a significant increase in heart weight and heart weight/body weight ratio. Hemodynamic and morphological studies were performed in one group. Thyroxine-treated rats showed a characteristic cardiovascular hyperdynamic state, such as tachycardia and augmented rate of contraction, but no evidence of heart failure such as elevated end-diastolic pressures. The cardiac cells in hyperthyroid rats had a significantly larger diameter and more mitochondria than did those of the control rats. In another group the activities of cardiac enzymes involved in energy utilization and liberation were measured biochemically and compared with those of normal controls. Hyperthyroidism resulted in increased specific activity of cytochrome C oxidase and actomyosin ATPase in the myocardium. The specific activity of long-chain acyl-CoA synthetase, carnitine palmityl-transferase, carnitine acetyltransferase, malate dehydrogenase and citrate synthase showed a moderate to marked increment, whereas the specific activity of lactate dehydrogenase and pyruvate kinase remained at the control values. These results suggest that in hyperthyroid rat hearts the functions of both energy liberation and utilization systems are enhanced to meet the added workload. Moreover, the increased activity of the enzymes participating in fatty acid metabolism suggest that in thyroxine-induced hypertrophic and hyperdynamic rat hearts, fatty acids contribute more to the energy supply than do carbohydrates.

Actomyosin↗

PubMedDate not supplied

Changes on levels of B6 vitamin and aminotransferase in the liver of diabetic animals.

We measured aminotransferase activity and vitamin B6 content in the livers of diabetic mice. Two different types of mice were used for the measurements, spontaneously non-obese diabetic (NOD) or alloxan-induced diabetic (Allo) mice, and control mice were either non-diabetic NOD or Institute of Cancer Research (ICR). The liver of diabetic mice had more aspartate aminotransferase (AST) activity than those of normal mice. The diabetic livers also had more vitamin B6 than did normal livers, and pyridoxamine (PM) levels were particularly high but pyridoxal (PL) levels were not. ICR livers showed hepatic alanine aminotransferase activities inversely correlated with blood glucose concentrations, while diabetic livers did not. The abundance of AST and B6 in the diabetic liver is consistent with the great need for gluconeogenic substrate there. This is understandable in that most aminotransferases require B6 vitamins, and especially the correlation between s-AST and PM levels was recognized in the diabetic liver. Conversely, the AST and PM levels were negatively correlated in normal mice. A metabolic shift towards gluconeogenesis apparently produces more B6 and PM while it induced holo-AST synthesis.

Alanine Transaminase↗

PubMedDate not supplied

Age-related changes in cerebral white matter measured by computed cranial tomography.

Changes in the cerebral white matter in relation to aging were studied quantitatively by computed cranial tomography (CT) in 70 healthy subjects aged 30 to 94 years. There were no age-related changes in the CT number of the white matter (WMCT) in 41 younger subjects aged 30 to 65 years. But, there was a significant negative correlation between age and the WMCT in 29 elderly subjects aged 66 to 94 years. Brain atrophy was significantly correlated with the WMCT. The WMCT decreased with aging even in neurologically healthy elderly persons.

Adult↗

PubMedDate not supplied

Comparative effects of pioglitazone, glibenclamide, and voglibose on urinary endothelin-1 and albumin excretion in diabetes patients.

Urinary endothelin (ET)-1 excretion is present in non-insulin dependent diabetes (NIDDM) patients with microalbuminuria, and an increase in circulating ET-1 precedes the microalbuminuric phase of renal injury related to diabetes. The aim of the present study was to determine whether various drugs alter urinary ET-1 levels and urinary albumin excretion (UAE) in NIDDM patients with microalbuminuria. Forty-five NIDDM patients with microalbuminuria were randomly assigned to three groups: those treated with pioglitazone at 30 mg/day (n=15), those treated with glibenclamide at 5 mg/day (n=15), and those treated with voglibose at 0.6 mg/day (n=15). Patients received these drugs for 3 months. UAE, urinary ET-1, and plasma ET-1 levels were measured in these patients before and after treatment. Before treatment, UAE, urinary ET-1, and plasma ET-1 levels differed little among the three groups. UAE in the 45 NIDDM patients (156.2+/-42.8 microg/min) was greater than that in 30 healthy controls (8.2+/-2.6 microg/min) (P<.001). Urinary ET-1 levels in the NIDDM patients (8.7+/-1.3 ng/g urinary creatinine (UC)) were significantly higher than that in the controls (2.4+/-0.2 ng/g UC) (P<.01). Plasma ET-1 levels, however, in the NIDDM patients (1.3+/-0.4 pg/ml) did not differ significantly from the levels in healthy controls (1.0+/-0.6 pg/ml). Pioglitazone but no glibenclamide or voglibose reduced UAE from 142.8+/-42.2 to 48. 4+/-18.2 microg/min (P<.01) and urinary ET-1 levels from 8.6+/-1.3 to 3.4+/-0.5 ng/g UC (P<.01). These data suggest pioglitazone to be effective in reducing UAE and urinary ET-1 concentrations in NIDDM patients with microalbuminuria.

Albuminuria↗

PubMedDate not supplied

Expression of cysteine proteinases and their inhibitor, cystatin beta, in cultured rat mesangial cells.

Matrix expansion in the glomerular mesangial area is observed in diabetic nephropathy. Intracellular breakdown of long-lived proteins was lower in mesangial cells in the high glucose medium than that in the control medium. Enzymatic activity of cathepsin L increased 1.4-fold after 6 h of treatment with the high glucose, and then declined gradually to 72% of control cells after treatment for 36 h. Change in the enzyme activity of cathepsin B showed a similar time course but less magnitude than that of cathepsin L. Immunoblot analysis with anti-cathepsin L antibody showed that change in the enzyme activity of cathepsin L was due to the change in the amount of cathepsin L, and that with anti-cathepsin B antibody showed no change in the amount of cathepsin B in the mesangial cells treated with high glucose. Intracellular cathepsin activities were controlled not only by the amounts but also by the inhibitor cystatin beta. Immunoblot analysis with anti-cystatin beta antibody showed that intracellular levels of cystatin beta increased slightly after 24 h of treatment with high glucose. These changes were derived from changes in mRNA level. These results, therefore, demonstrated that the decrease of intracellular protein breakdown in mesangial cells treated with high glucose medium was due to both suppression of cathepsins and increase of cystatin beta.

Animals↗

PubMedDate not supplied

Multidetector SPECT scanner for brain and body: system performance and applications.

A multidetector whole-body single photon emission computed tomography (SPECT) scanner has been developed for high-resolution dynamic SPECT imaging. The scanner consists of three detector rings with 128 NaI crystals (14 x 26 x 30 mm) in each ring, providing three tomographic images at 30 mm intervals. This system uses a rotation of collimator around the patient combined with the detector rotation for fine data sampling. The in-plane spatial resolution is 14.2 mm (full width of half maximum) with high-resolution (HR) collimator, 22.0 mm with high-sensitivity (HS) collimator, and 10.6 mm with high-resolution brain (HRB) collimator. The axial resolution is 24.0, 34.0, and 23.5 mm with HR, HS, and HRB collimator, respectively. The sensitivity measured with a 20% energy window for 99mTc in a 20 cm diameter phantom is 5.7, 17.0 and 6.6 kcps/muCi/ml with HR, HS, and HRB collimator, respectively. This scanner allows dynamic SPECT imaging both for brain and body organs with good spatial resolution.

Brain↗

PubMedDate not supplied

Elevation of serum levels of metalloproteinase-1, tissue inhibitor of metalloproteinase-1 and type IV collagen, and plasma levels of metalloproteinase-9 in polycystic kidney disease.

Several studies on polycystic kidney disease (PKD) have revealed a number of extracellular matrix (ECM) abnormalities, suggesting that an abnormal ECM plays a role in the development of tubular cysts. Cystic kidney tubules synthesize and secrete high levels of metalloproteinases (MMP), which may participate in the restructuring of the tubular basement membrane. The aim of the present study was to determine whether serum MMP-1, tissue inhibitor of metalloproteinase (TIMP)-1, and type IV collagen levels, and plasma MMP-9 levels were altered in patients with PKD. Sixteen patients with autosomal dominant polycystic kidney disease, and 20 healthy controls were included in this study. Specific enzyme immunoassays were used to measure MMP-1, MMP-9, TIMP-1, and type IV collagen levels. Serum MMP-1 (14.8 +/- 3.6 ng/ml), TIMP-1 (288.6 +/- 48.6 ng/ml), and type IV collagen (192.6 +/- 38.8 ng/ml) concentrations, and plasma MMP-9 (90.2 +/- 26.8 ng/ml) concentrations in patients with PKD were significantly higher than those in healthy controls (MMP-1; 6.6 +/- 0.9 ng/ml, p < 0.01, MMP-9; 36.4 +/- 12.2 ng/ml, p < 0.01, TIMP-1; 164.6 +/- 22.8 ng/ml, p < 0.01, and type IV collagen; 86.6 +/- 14.2 ng/ml, p < 0.001). The present results suggest that ECM abnormalities associated with cystic kidney may result from aberrant degradation as well as from abnormal synthesis of ECM components.

Collagen↗

PubMedDate not supplied

The urinary podocyte as a marker for the differential diagnosis of idiopathic focal glomerulosclerosis and minimal-change nephrotic syndrome.

BACKGROUND/AIMS: Detection of podocytes in the urine sediment of children indicates that severe podocyte injury occurred in the glomerulus. Focal glomerulosclerosis (FGS) and minimal-change nephrotic syndrome (MCNS) are kidney diseases characterized by massive proteinuria. The aim of the present study was to determine whether urinary podocytes can be detected in patients with idiopathic FGS or MCNS and whether immunosuppression therapy alters these cells. METHODS: Twenty patients with MCNS (nephrotic stage, n = 12; remission stage, n = 8), 15 patients with FGS and 20 healthy controls were included in the present study. Urinary podocytes were stained by immunofluorescence. All patients with MCNS at the nephrotic stage received prednisolone for 6 months, and all patients with FGS received some form of immunosuppression therapy including prednisolone, cyclophosphamide or mizoribine for 12 months. RESULTS: The 12 nephrotic-stage MCNS patients achieved remission after treatment. Seven of the 15 FGS patients also achieved remission, but the other 8 remained in the nephrotic stage. Urinary podocytes were not detected in any patient with MCNS nor were they detected in healthy controls. Urinary podocytes were detected in all FGS patients (mean, 4.2 cells/ml) before treatment and the number of cells decreased in the 7 patients who achieved remission. The number of podocytes was unchanged in the other 8 patients even after treatment. CONCLUSION: Urinary podocytes may be a useful diagnostic indicator for differentiation between FGS and MCNS. These cells may also mark disease progression in cases of FGS.

Adult↗