Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:2.7.10.2 (focal adhesion kinase)
 44,029 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The authors present data from a group of 55 patients suffering from chronic renal diseases. Twenty-two were treated by haemodialysis; the rest had serum creatinine levels ranging from normal to 950 mumol/l. The molar esterification rats [MER] and total cholesterol [TCH] values decreased parallel to the gradual extinction of renal function. A reduced fractional esterification rate [FER] was found in about two thirds of the dialysed patients and in about half of those whose kidney function was still relatively well preserved. It can thus be concluded that reduction of FER values indicative of a disturbance of cholesterol metabolism can already be detected in the early stages of chronic nephropathies.
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PMID:Lecithin cholesterol acyltransferase activity in chronic nephropathies. 647 41

To determine the effects of low-dosage organophosphate administration on exercise in a hot environment, malathion (7.5 mg/day, 4 days) was administered IP to rats, and effected a 35% (p less than 0.01) reduction in plasma cholinesterase levels. Treadmill endurance (9.14 m/min, no incline, 35 degrees C ambient) was unaffected when the animals were exercised to hyperthermic exhaustion (Tre approximately 43 degrees C). While rates of heat gain were similar between groups, malathion-treated rats displayed higher Tsk (p less than 0.05) at a number of sampling times during the treadmill run. While creatine phosphokinase levels were unaffected by either cholinesterase inhibition or exercise in the heat, lactate dehydrogenase activities were increased (p less than 0.01) in both groups following hyperthermic exhaustion. Although plasma levels of lactate, potassium, urea nitrogen, and creatinine were all significantly (p less than 0.01) increased as a result of exercise in the heat, these increments were not exacerbated by cholinesterase inhibition. Results generally indicated that at this moderate level cholinesterase inhibition, malathion administration did not adversely affect physiological, physical, or thermoregulatory efficacy.
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PMID:Malathion administration: effects on physiological and physical performance in the heat. 665 21

The authors measured plasmatic beta 2-microglobulin in 42 type II diabetes patients, whose 23 microalbuminuria (group A) and 19 normal albuminuria (group B), and in 20 healthy control subjects (group C) comparable for sex and age. Beforehand, everybody was subject to diagnostic verification to exclude other simultaneous diseases. The glomerular filtration rate, measured by creatinine clearance did not show statistical significance between three groups as well as duration of diabetes and levels of glycosylated hemoglobin between group A and B. Plasmatic beta 2-microglobulin was 3.16 +/- 0.9, 2.1 +/- 0.6, 2.0 +/- 0.9 mg/L respectively in the groups A, B and C (p < 0.001 A vs B and A vs C). The authors think in type II diabetic subjects with microalbuminuria can be an early and mild decrease of FGR. The measurement of plasmatic beta 2-microglobulin rather than creatinine clearance could be a suitable method to show it.
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PMID:[Plasma beta 2-microglobulin in patients with non-insulin-dependent diabetes mellitus]. 775 32

A high performance liquid chromatography (HPLC) with isocratic ion-pair-reversed-phase separation and simultaneous UV-detection at 232 nm and 292 nm is proposed as a method for the simultaneous determination of uric acid and creatinine in serum. The only sample preparation required is an appropriate dilution with the eluent and membrane filtration on non-adsorbent 0.2 micron membrane-filtration-devices. The inaccuracy of the method has been determined for NIST-SRM-909 (n = 10) and was + 0.5% for creatinine as well as for uric acid. The imprecision in this case was 0.8% for both analytes. The within-run imprecision for creatinine/uric acid was 0.4-0.5%/0.2-0.4% in the case of standards and 0.6-0.8%/0.4-0.7% in the case of serum-pools. The between-run imprecision for creatinine/uric acid obtained from serum pools was 0.8-1.1%/0.7-1.0%. The results for creatinine have been compared to those from an isotope dilution-gas chromatography-mass spectrometry using [13C, 15N2]creatinine as internal standard and selected mass detection at m/e = 329 and m/e = 332. The results for uric acid have been compared to an HPLC-method published previously (Kock R et al. J Clin Chem Clin Biochem 1989; 27:157-62). The method comparisons (n = 55) for the new combined method presented versus the reference method for creatinine and the candidate reference method for uric acid resulted in coefficients of correlation of r = 1.000 for both analytes. The new combined method presented is useful for the analysis of patient samples where the classical photometric procedures do not give reliable results, as often observed in monitoring after transplantation surgery.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A method for the simultaneous determination of creatinine and uric acid in serum by high-performance-liquid-chromatography evaluated versus reference methods. 775 38

The extracellular pH (pHe) in solid tumors is frequently lower than the pHe in normal tissues, but the intracellular pH (pHi) is regulated to physiological levels. Cell killing can be achieved in an acidic environment in tissue culture by nigericin, which acidifies cells by transporting H+ from the extracellular space into the cytoplasm; this cell killing can be enhanced when used with 5-(N-ethyl-N-isopropyl)amiloride (EIPA), a potent inhibitor of membrane-based Na+/H+ exchange, which plays a major role in the regulation of pHi (R. P. Maidorn; E. J. Cragoe; I. F. Tannock, Br. J. Cancer 67:297-303; 1993). We have therefore assessed the ability of nigericin and EIPA to kill cells in two murine solid tumors (the KHT fibrosarcoma and the EMT-6 sarcoma). Hydralazine, which reduces tumor blood flow, or glucose, which stimulates glycolysis leading to accumulation of lactate, were also administered to mice to lower pHe in the tumors. We observed only a small decrease in the surviving fractions of cells in the tumors when tolerated doses of nigericin and EIPA were given IP to tumor-bearing mice. When nigericin and EIPA were combined with administration of hydralazine, the surviving fraction of cells in both tumors was reduced by a factor of 0.01, but there were minimal effects on growth delay. Administration of glucose with nigericin and EIPA led to a smaller reduction in surviving fraction of the KHT tumor (by approximately 0.1), although glucose was more effective than hydralazine in lowering the mean tumor pHe. When KHT tumors were treated with 15 Gy X-rays followed immediately by nigericin, EIPA, and hydralazine, a reduced surviving fraction as well as an increase in tumor growth delay was observed compared to radiation alone; however, there was little evidence to suggest that these agents were selectively toxic to the cells that survived radiation. Nigericin and EIPA, with or without hydralazine, had minimal effects on normal tissues, as assessed by changes in body weight, number of leukocytes, and serum creatinine levels. We conclude that pharmacological effects to acidify cells and to prevent regulation of pHi under the acidic conditions that exist in solid tumors can lead to moderate levels of cell killing, if additional strategies are used to lower tumor pHe.
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PMID:Antitumor activity of nigericin and 5-(N-ethyl-N-isopropyl)amiloride: an approach to therapy based on cellular acidification and the inhibition of regulation of intracellular pH. 786 1

We have investigated the effect that some products of protein catabolism have on endothelium-dependent and -independent relaxation of rabbit aorta rings precontracted with phenylephrine (PE). All the products tested, i.e., creatinine (CRT), guanidinosuccinic acid (GSA), urea (UR), guanidine (GND) and methylguanidine (MG), are structurally related to L-arginine (L-ARG), the substrate for nitric oxide (NO) biosynthesis which accounts for the biological properties of endothelium-derived relaxing factor (EDRF). Endothelium-derived NO (EDNO) release was induced by agents acting via a receptor- [acetylcholine (ACh)] or a nonreceptor-mediated mechanism (calcium ionophore A23187), and the endothelial-independent relaxation was induced by the NO donor glyceryl trinitrate (GTN). CRT (0.1-10 mM) did not modify the endothelium-dependent relaxation caused by ACh or A23187 but produced a small increase in the response to the endothelium-independent vasorelaxant GTN. Concentrations of GSA up to 1 mM did not affect the relaxation of rabbit aortic rings induced by either ACh or A23187, but at 10 mM, GSA enhanced the relaxation produced by these agents. UR (1-100 mM) inhibited, in a concentration-dependent manner, the relaxation induced by ACh, but not that caused by A23187 or GTN. By comparison, GND and MG (0.1-10 mM) produced a concentration-related inhibition of both ACh- and A23187-induced relaxation. The inhibition by these compounds was either completely or partially reversed by L-ARG. In contrast, the relaxation induced by GTN was inhibited only by higher concentrations (10 mM) of GND or MG. These results indicate that some products of protein catabolism can reduce EDNO formation in vitro.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of some products of protein catabolism on the endothelium-dependent and -independent relaxation of rabbit thoracic aorta rings. 835 96

Absidiosis was produced experimentally in rabbits by intravenous inoculation of 1.4 x 10(5) spores of Absidia corymbifera. Infected rabbits exhibited a rise in body temperature, anorexia, dullness, listlessness, diarrhoea, occasional blindness, convulsions and death in some cases. Mortality occurred mainly between 6 to 9 days post infection (DPI) and overall mortality was 50 per cent during the three week observation period. No significant difference was observed in erythrocytic indices viz., Hb, PCV, TEC in control and infected rabbits. However, erythrocyte sedimentation rate was considerably increased in the infected rabbits. A state of leucocytosis was observed in the infected rabbits, which was due to increase in the relative percentage of neutrophils and decrease in lymphocytes. There was a significant increase in blood urea nitrogen concentrations of infected rabbits from 3 to 14 DPI as compared to controls, but serum creatinine values were not significantly altered at any stage of infection. The cause of death was attributed to kidney failure and uraemia in infected rabbits. The rabbit was found to be a suitable model for the study of absidiosis.
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PMID:Experimental Absidia corymbifera infection in rabbits: clinicopathological studies. 881 36

The effect of the blockade of the renin angiotensin system (RAS) on thermoregulatory, cardiovascular and renal function during moderate exercise in a hot [mean (SEM) 34.4 (0.1) degrees C] environment was evaluated. Six men and three women cycled at 60% peak oxygen uptake for 45 min following acute administration of a placebo (PLAC) or enalapril (ENAL), an angiotensin converting enzyme inhibitor (ACE-I). Resting mean arterial pressure (MAP) was reduced by ENAL, but the pressor response to exercise was unaffected [delta MAP = 7.8 (1.4)mmHg for both trials (P > 0.05)]. Peak esophageal temperature [T(es) = 38.7 (1.0) degrees C (PLAC) vs 38.4 (0.2) degrees C (ENAL)] and mean skin temperatures [Tsk = 36.5 (0.1) degrees C (PLAC) vs 36.6 (0.1) degrees C (ENAL)] were similar for both drug treatments during the exercise. Both aldosterone and plasma renin activity (PRA) increased five fold above resting values during exercise; however, only the PRA response [16.7 (3.2) ng angiotensin I (Ang I).ml-1.h-1 (ENAL) vs 7.4 (1.2)ng Ang I.ml-1.h-1 (PLAC)] was significantly altered by ENAL treatment (P < 0.05). Urine flow, sodium excretion and glomerular filtration rates, determined from creatinine clearance, were similarly reduced following exercise for both ENAL and PLAC treatments. These results suggest acute administration (5 mg) of ACE-I does not impair thermoregulatory, cardiovascular or renal responses during moderate exercise in the heat.
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PMID:Influence of angiotensin II blockade during exercise in the heat. 892 29

A prospective semi-longitudinal study was undertaken to determine if urinary neopterin was a predictor for survival in HIV-positive patients. One hundred and one HIV-positive subjects attending a department of genitourinary medicine over a 41-month period were included. Survival data were analysed 6 months after the end of recruitment. Ninety-two subjects were followed up for a minimum of 6 months. Survival figures at 1 and 2 years were 93% (SE 3%) and 79% (SE 5%). There was an inverse relationship between urinary neopterin excretion and 1 and 2-year survival. Two-year survival fell from 70% (SE 6%) for neopterin levels > or = 300 mmol/mol creatinine to 25% (SE 9%) for levels > or = 700 mmol/mol creatinine (P < 0.001). Urinary neopterin may be a useful non-invasive technique in predicting survival in HIV-positive patients.
Int J STD AIDS 1998 Jun
PMID:Urinary neopterin as a prognostic index of survival time in HIV-1 infection. 967 Dec 45

To investigate how various levels of exposure affect the metabolic activation pathways of benzene in humans and to examine the relationship between urinary metabolites and other biological markers, we have developed a sensitive and specific liquid chromatographic-tandem mass spectrometric assay for simultaneous quantitation of urinary S-phenylmercapturic acid (S-PMA) and trans,trans-muconic acid (t,t-MA). The assay involves spiking urine samples with [13C6]S-PMA and [13C6]t,t-MA as internal standards and clean up of samples by solid-phase extraction with subsequent analysis by liquid chromatography coupled with electrospray-tandem mass spectrometry-selected reaction monitoring (LC-ES-MS/MS-SRM) in the negative ionization mode. The efficacy of this assay was evaluated in human urine specimens from smokers and non-smokers as the benzene-exposed and non-exposed groups. The coefficient of variation of runs on different days (n = 8) for S-PMA was 7% for the sample containing 9.4 microg S-PMA/l urine, that for t,t-MA was 10% for samples containing 0.07 mg t,t-MA/l urine. The mean levels of urinary S-PMA and t,t-MA in smokers were 1.9-fold (P = 0.02) and 2.1-fold (P = 0.03) higher than those in non-smokers. The mean urinary concentration (+/-SE) was 9.1 +/- 1.7 microg S-PMA/g creatinine [median 5.8 microg/g, ranging from not detectable (1 out of 28) to 33.4 microg/g] among smokers. In non-smokers' urine the mean concentration was 4.8 +/- 1.1 microg S-PMA/g creatinine (median 3.6 microg/g, ranging from 1.0 to 19.6 microg/g). For t,t-MA in smokers' urine the mean (+/-SE) was 0.15 +/- 0.03 mg/g creatinine (median 0.11 mg/ g, ranging from 0.005 to 0.34 mg/g); the corresponding mean value for t,t-MA concentration in non-smokers' urine was 0.07 +/- 0.02 mg/g creatinine [median 0.03 mg/g, ranging from undetectable (1 out of 18) to 0.48 mg/g]. There was a correlation between S-PMA and t,t-MA after logarithmic transformation (r = 0.41, P = 0.005, n = 46).
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PMID:Determination of the urinary benzene metabolites S-phenylmercapturic acid and trans,trans-muconic acid by liquid chromatography-tandem mass spectrometry. 1022 5


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