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Biomedical subjects

Z K Shihabi

Publications and source records attributed to Z K Shihabi.

At least 19 recordsLinked to original sources

Microalbuminuria: frequency and clinical significance in hospital patients.

We investigated the frequency and the clinical significance of microalbuminuria (UA) in 312 hospital patients suspected of renal disorders, but with normal or borderline levels of urinary total protein (UTP). Approximately one-third of the patients with urinary total protein < 300 mg/g creatinine had microalbuminuria, above the reference interval (< 32 mg/g creatinine). In contrast, only 10% of the patients with elevated total urinary protein above the reference interval (> 200 mg/g creatinine) did not have microalbuminuria. About half of the patients with elevated UA had diabetes mellitus, hypertension, an immune-related disorder, or had undergone a recent renal transplant. About half of the patients with borderline elevated UTP (100 to 300 mg/g creatinine) did not have any obvious renal problem. These data demonstrate that: 1) microalbuminuria occurs very commonly in hospital patients, 2) it is a more sensitive and specific assay for the early detection of many renal disorders compared to urinary total protein, especially when the latter test is normal or borderline elevated; and 3) a thorough patient history is required for interpretation of microalbuminuria in diabetes to eliminate other complicating factors.

Aged

Iohexol in serum determined by capillary electrophoresis.

Iohexol, a nonionic compound used as a contrast medium for angiography and as a measure of the glomerular filtration rate, was quantified in serum by capillary electrophoresis. Comparable results were obtained for serum samples deproteinized with acetonitrile or analyzed directly after 50-fold dilution with borate buffer. Serum samples were electrophoresed for 2.6 min at 12 kV in a borate buffer with detection at 254 nm and with 3-isobutyl-1-methylxanthine as internal standard. Acetonitrile deproteinization gave a greater sensitivity than did sample dilution. Between-run CVs were between 4.7% and 6.7%, and within-run CVs were between 2.5 and 3.2%. Analytical recoveries were 95-105%. Results of the method compared well with those by high-performance liquid chromatography (slope 0.96, intercept 0.005 g/L). This method demonstrates the potential of capillary electrophoresis for rapid and simple quantification of small molecules.

Acetonitriles

Serum and tissue carnitine assay based on dialysis.

Carnitine (L-beta-hydroxy-gamma-trimethylaminobutyric acid) aids mitochondrial energy production by transferring fatty acids across the membranes for beta-oxidation. We describe here a modified enzymatic assay for free serum and tissue carnitine based on dialysis to remove interfering substances in the serum, with subsequent conversion of carnitine to the acyl derivative by carnitine acetyltransferase (EC 2.3.1.7) in the presence of 5,5'-dithiobis-(2-nitrobenzoic acid). The method compared well with a radioenzymatic assay. The reference interval for serum is 28-70 mumol/L. Patients with advanced diabetes and those undergoing valproic acid treatment displayed lower mean values; a statistically significant number of them showed serum carnitine values below the reference interval. The method was also applied to carnitine measurement in cerebrospinal fluid and human tissues.

Carnitine

Ethanol preference in the Harrington derivation of the Maudsley Reactive and Non-Reactive strains.

Ethanol intake was explored in the Harrington derivation of the Maudsley Reactive and Maudsley Non-Reactive rat strains (MR/Har and MNRA/Har). When 5% and 10% ethanol solutions were presented as the sole source of fluid (1-bottle test), MR/Har rats, respectively, ingested 15% more, or 9% less, than their baseline water intake, whereas MNRAs ingested 6% less, or 42% less than their baseline intake. However, because MNRA/Har rats drank significantly more water than MR/Har's under ad libitum conditions (MNRA/Har, 46.6 +/- 1.83 ml; MR/Har 32.45 +/- 1.64 ml/24 hr), males and females of the two strains ingested a similar amount of ethanol in the 1-bottle test (5% ethanol, 4-7; 10% ethanol, 6-12 g/kg body weight/24 hr). In 2-bottle free-choice tests administered after an extended period of forced ethanol consumption, MR/Har male and female rats exhibited a strong ethanol preference (X = 80%) and consumed a larger amount of ethanol (MR/Har, 7-13; MNRA/Har, 6-9 g/kg body weight/24 hr) than MNRA/Har's. Across all conditions, females of both strains ingested a greater relative amount of ethanol than males. The strain difference in ethanol preference was found to be independent of prior exposure to ethanol because it was also found when 2-bottle free-choice tests were carried out in naive animals (Experiment 2). The pattern of development of ethanol preference in individual animals was characterized by abrupt onset, after variable periods of exposure to the 2-bottle choice test, and maintenance of strong ethanol preference thereafter. The extensive behavioral and biological definition of the Maudsley strains is a valuable asset in attempting to elucidate the biobehavioral correlates of ethanol preference.

Alcohol Drinking

The effect of a high salt diet and gender on blood pressure, urinary protein excretion and renal pathology in SHR rats.

A high salt diet produced increases in SBP, urinary protein excretion (UPE) and renal vascular lesions (RVL) across groups of male and female SHR rats which were allowed to develop moderate or excessive increases in SBP. A highly significant linear relationship between SBP and log-transformed UPE was found when the data from all groups were analyzed together. Males developed high blood-pressure more rapidly, and exhibited more severe RVL and greater UPE than females. Two results prevent the conclusion that the elevated UPE was simply due to the adverse effects of high BP on the kidney. First, the relationship between SBP and UPE across groups could not be demonstrated when regression analyses were performed within individual dietary sub-groups. Secondly, gender differences in UPE were highly significant by analysis of covariance adjusting for individual differences in SBP. The increases in SBP and UPE may be independent consequences of ingestion of a high salt diet.

Animals

Albuminuria vs urinary total protein for detecting chronic renal disorders.

A literature review and our own data are presented to demonstrate that urinary albumin (UA) excretion increases in many renal disorders and that it offers a far more sensitive indicator than the commonly used urinary total protein (UTP) for the early detection of renal involvement in many chronic diseases such as diabetes mellitus, hypertension, and systemic lupus erythematosus. In many individuals with these disorders, UA increases severalfold, even while UTP remains within the reference interval. UA is also more suited than UTP for following therapeutic responses in these slowly progressive renal disorders. Increases in UA are associated with increased mortality. UTP measurements are plagued with many analytical problems, whereas UA is much easier to standardize. We recommend that both UA and UTP be measured when quantitative urine protein assays are ordered, especially when the UTP is less than 300 mg/g of creatinine.

Albuminuria

Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides.

The present study has indicated that significant shifts in plasma, urinary, and tissue taurine and in non-taurine dialyzable amines occur in the STZ-induced diabetic rat, especially in the kidney. Taurine administration at relatively low dosage ameliorated only kidney taurine concentration. Anticipated alterations in plasma glucose and creatinine were observed but neither of these changes was affected by taurine administration. Similarly, urinary output of creatinine, glucose, and NAG increased significantly among diabetic rats, but none of these were detectably influenced by taurine. Increases in plasma triglycerides observed in STZ-induced diabetes appear to be attenuated by taurine administration, and although cholesterol concentrations were lower in taurine-treated rats, the differences were not statistically significant. These findings should encourage further studies of these effects in rats as a useful model for several complications of human diabetes including atherosclerosis, retinopathy, and nephropathy.

Amino Acids

Plasma fibrinogen levels in type II diabetics.

Plasma fibrinogen levels measured by an immunoassay method on 170 type II diabetic patients exhibited a bimodal distribution with one small population demonstrating levels greater than those of the normal reference range. The mean plasma level of fibrinogen in the type II diabetics was higher than that of the normal population. Spearman's correlations demonstrated statistically significant positive relationships in type II diabetic patients between fibrinogen levels and fasting glucose levels, serum cholesterol, glycosylated hemoglobin and urinary albumin excretion rate. These relationships suggest that increased plasma fibrinogen may be another marker for coronary heart disease complications encountered by diabetics.

Albuminuria

Screening diabetic patients for microalbuminuria.

Abnormal rates of urinary albumin excretion have been shown to predict the development of nephropathy and may signal atherosclerotic disease in diabetic patients. This study demonstrated the feasibility of measuring microalbuminuria in diabetic patients from a large family practice population. Although only one half of the 473 diabetic patients offered free screening took advantage of the testing, those participating did not differ in terms of sex, race, type of diabetes, mean age, systolic blood pressure, and fasting blood glucose levels from those not electing to participate. Over 40% of those screened had abnormally elevated albumin excretion rates as defined as greater than 0.02 g of albumin per gram of creatinine. Those participating in the screening perceived the process as useful and were able to comply with directions for overnight urine collection. Results show that screening for microalbuminuria in diabetic patients cared for by family physicians is feasible, simple, and inexpensive. Interventions to slow or reverse the progression of abnormal microalbuminuria and future risk for nephropathy in those with diabetes are underway.

Adult

Microtransferrinuria and microalbuminuria. I. In the diabetic human.

We studied albumin, transferrin and total protein excretion in the urine of 110 diabetics visiting a family practice department. Of these patients 18.2% had an elevated total urinary protein above the reference range (greater than 200 mg/g creatinine). Of the remaining patients (normoproteinuria), 25.5% have elevated transferrin (greater than 0.9 mg/g creatinine) while 18.8% have elevated albumin (greater than 32 mg/g creatinine). The correlation coefficient between transferrin and albumin in urine when total urinary protein is normal was 0.77. Moderate exercise increased urinary transferrin in normal subjects 950%, while for albumin the increase was 440%. These data demonstrate the usefulness of microtransferrinuria, a potentially more sensitive indicator than microalbuminuria for diabetic nephropathy.

Albuminuria

Microtransferrinuria and microalbuminuria. II. In the rat.

We studied albumin and transferrin excretion in the normal and diabetic rat: (1) The rat secretes small concentrations of albumin and transferrin in the urine. (2) The secretion depends on the strain and was highest in the Kyoto spontaneously hypertensive rat. (3) The secretion of these two proteins in the rat is quite dependent on age and sex. The level increases dramatically with age. The secretion is much higher in the male compared to the female. This difference is observed after puberty. The changes in transferrin relative to those in albumin are much higher. (4) In streptozotocin-induced diabetes, the concentration of albumin and transferrin expressed as milligrams per liter decreases; however, the output/24 h or per gram creatinine is increased with a greater increase in transferrin output relative to that of albumin. The similarities and differences between excretion of these two proteins in the human and the rat as well as their importance are discussed.

Aging

Serum amphotericin-B assay by scanning spectrophotometer.

We describe a simple, specific, 3-min assay for amphotericin-B in serum based on the absorbance at 408 nm and spectral scanning between 450 and 350 nm of the drug in acetonitrile extracts. The method correlated well with a high-performance liquid chromatographic method.

Amphotericin B

Automated analysis for taurine in biological fluids and tissues.

We have developed an automated method of analysis for taurine, based on incorporating an ion-exchange chromatography column into the continuous-flow AutoAnalyzer (Technicon). After removal of proteins and peptides by dialysis, taurine is selectively eluted from an ion-exchange column and reacted with o-phthaldialdehyde to yield a fluorescent compound. The advantages of this method are: full automation with no need for sample deproteinization or cleanup; sensitivity, detecting as little as 5 mumol/L; speed (20 samples per hour); and flexibility. It can be used for assaying taurine in urine, plasma, cerebrospinal fluid, and tissue homogenates. This method can be adapted for assays of other metabolites.

Amino Acids

Galactosemic nephropathy in the rat.

The effect of 30% galactose feeding on kidney function and structure was compared to the effect of streptozotocin-induced diabetes in the rat. In the galactose-fed rats there was increased urine volume (500%), creatinine clearance (40%), urinary albumin excretion (100%), urinary N-acetyl glucosaminidase (600%) and relative kidney weight (21%). These changes were similar to that observed in streptozotocin-induced diabetic animals. Galactitol in the kidney cortex of galactose-fed rats was increased 4 times similar to that observed for sorbitol in the streptozotocin-induced diabetic animals. Glycosylated hemoglobins were also increased in both galactose-fed animals and streptozotocin-treated animals. These data suggest that galactose feeding may be a useful model for investigating some aspects of diabetic nephropathy.

Acetylglucosaminidase