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Biomedical subjects

W G Guder

Publications and source records attributed to W G Guder.

At least 19 recordsLinked to original sources
PubMed1992

Osmolytes.

The cells of the renal medulla osmotically adapt to chronic alterations in extracellular tonicity by appropriate changes in the intracellular contents of organic osmoeffectors. The major organic osmolytes are glycerophosphorylcholine, betaine, myo-inositol, sorbitol, and, possibly, taurine. When the concentrations of poorly permeant external solutes are acutely reduced, cells that have been adapted to high tonicities rapidly release organic osmolytes via specific transmembrane transport pathways. In contrast, when medullary cells are depleted of organic osmolytes, osmolyte accumulation on acute elevation of external tonicity is slow and involves stimulation of uptake, intracellular de novo synthesis, or inhibition of intracellular degradation, and is preceded by increased intracellular electrolyte concentrations. The available evidence suggests that this rise in intracellular ionic strength plays an important role in the initiation of those processes responsible for full adaptation of renal medullary cells to high tonicities. Recently, complementary DNAs encoding a myo-inositol and a betaine transporter have been isolated.

Animals↗
PubMed1992

Osmolytes in renal medulla during rapid changes in papillary tonicity.

The effect of acute changes in extracellular tonicity on cell electrolyte concentrations at the renal papillary tip and on organic osmolytes in different kidney zones was studied using electron microprobe analysis and high-performance liquid chromatography in four groups of rats: controls, 1- or 4-h water diuresis, and 4-h water diuresis followed by 30-min deamino-[Cys1,D-Arg8]vasopressin (ddAVP). The sum of the papillary interstitial concentrations of Na, K, and Cl was reduced from 981 mmol/kg wet wt in controls to 318 mmol/kg wet wt after 4-h diuresis and increased after ddAVP to 840 mmol/kg wet wt. In papillary collecting ducts intracellular electrolytes fell from 225 to 156 mmol/kg wet wt after 4-h diuresis and rose to 268 mmol/kg wet wt (significantly higher than control) after ddAVP. Organic osmolytes [sum of glycerophosphorylcholine (GPC), betaine, myo-inositol, and sorbitol] at the papillary tip decreased from 2,018 (control) to 1,037 mmol/kg protein after 4-h diuresis and did not increase after ddAVP. After ddAVP, cell P concentration, an index of cell GPC concentration, increased, indicating cell shrinkage. GPC concentration increased, indicating cell shrinkage. The results suggest that the concentrations of all osmoeffectors in papillary cells initially increase due to cell shrinkage in response to hypertonic stress. The higher intracellular ionic strength may be a signal for modulation of transport and metabolism of organic osmolytes.

Animals↗
PubMed1992

Renal sorbitol, myo-inositol and glycerophosphorylcholine in streptozotocin-diabetic rats.

The polyols, sorbitol and myo-inositol, seem to be involved in the development of diabetic complications of different organs. High concentrations of both polyols were found in kidney medulla in addition to trimethylamines. To investigate the influence of diabetes mellitus on the regulation of both polyols and glycerophosphorylcholine in kidney, these osmolytes were quantitated enzymatically along the corticopapillary axis in untreated, streptozotocin-diabetic and insulin-treated streptozotocin-diabetic rats. In control animals three individual osmolyte patterns were found: a steep gradient of sorbitol in the papilla, increasing amounts of glycerophosphorylcholine from the outer medulla to the papilla, and nearly equal amounts of myo-inositol in the renal medulla, decreasing towards the cortex. Diabetic rats exhibit an up to fourfold increase of inner medullary sorbitol, whereas myo-inositol was only elevated in the outer medulla. Glycerophosphorylcholine was lowered in the papillary tip and elevated in the outer medulla and cortex. Insulin treatment reduced sorbitol to a concentration between those of diabetic and control rats, caused a restoration of glycerophosphorylcholine in the papillary tip and outer medulla to control values, and increased cortical myo-inositol. These data confirm previous in vitro data, which show that papillary sorbitol specifically increases in hyperglycaemic states, thereby counteracting the increased extracellular tonicity due to elevated tissue glucose concentrations. Imbalance of extra- vs intracellular osmolality during insulin treatment may be involved in the pathomechanism of renal papillary necrosis.

Animals↗
PubMed1992

Markers for the diagnosis and monitoring of renal tubular lesions.

Single proteins and tubular enzymes have been proposed as markers to detect and differentiate prerenal, glomerular, tubular and postrenal forms of proteinuria and hematuria. By quantitation of total protein, albumin, alpha 1-microglobulin, IgG, alpha 2-macroglobulin and N-acetyl-beta,D-glucosaminidase (beta-NAG) activity it has become possible to clearly separate these forms by analysis of a single sample of second morning urine. When this program was applied to screening of hospital patients, albumin, total protein and NAG proved to be sufficient to exclude clinically relevant disturbances. alpha 1-Microglobulin was useful to separate primary glomerulopathies from tubulo-interstitial diseases. Glomerular and postrenal hematuria could be clearly separated by their different excretion rates of alpha 2-macroglobulin, if urine albumin concentration exceeds 100 mg/l. The results imply that wider application of these techniques can help to detect renal abnormalities at an earlier stage and differentiate their various forms by less invasive techniques.

Acetylglucosaminidase↗
PubMed1992

Carbohydrate and lipid metabolism of the renal tubule in diabetes mellitus.

Diabetic nephropathy not only involves vascular and glomerular changes but also affects tubular metabolism, structure and function. Under acute insulin withdrawal the tubular size increases with glomerular hyperfiltration. Insulin like growth factor 1 (IGF1) has been found to be a candidate mediator involved under these conditions. Tubular carbohydrate metabolism is characterized by gluconeogenesis in the proximal tubule, glycolytic enzymes in the distal segments and high aldose reductase activity in the structures of the renal papilla. In the diabetic state, gluconeogenesis is stimulated by changes of the acid base status. Mitochondrial glucose oxidation is decreased by inhibition of pyruvate dehydrogenase activity through preferential oxidation of fatty acids and ketone bodies. The increase in glycogen in distal tubule cells and sorbitol accumulated in papillary structures can be explained by the high extracellular glucose supply under diabetic conditions. Fatty acids taken up in excess of tubular energy needs accumulate in the nephron as triacylglycerols, mainly in the proximal convoluted tubule. Fatty acid oxidation is inhibited by ketone bodies in proximal and outer medullary tubules, leading to preferential oxidation of the latter under ketotic conditions. Ammonia formed during tubular metabolism of glutamine increases in metabolic acidosis but is suppressed by ketone bodies, leading to a nitrogen sparing effect of ketone bodies. All acute metabolic derangements are abolished, and normal metabolism reestablished by adequate insulin treatment in vivo.

Animals↗
PubMed1992

A new strategy for characterizing proteinuria and haematuria from a single pattern of defined proteins in urine.

Prerenal, glomerular, tubulointerstitial and postrenal proteinurias and haematurias are usually differentiated by a number of non-invasive and invasive diagnostic procedures. We have applied a new analytical strategy based on the observation that different urine protein patterns are excreted in normal, prerenal, renal and postrenal proteinurias and haematurias. When analysed by turbidimetric procedures urine albumin, IgG, alpha 1-microglobulin and alpha 2-macroglobulin can be used as marker proteins to characterize the degree of glomerular permeability, tubular protein reabsorption and postrenal bleeding respectively. Primary glomerulopathies (selective and non-selective) and tubulointerstitial nephropathies can be differentiated by plotting the excretion rates of IgG or alpha 1-microglobulin against that of albumin. Postrenal contaminations are detected by quantitative turbidimetric assay of the high molecular weight proteins, alpha 2-macroglobulin and IgG. In postrenal bleeding, with albumin concentrations above 100 mg/l, the relative excretion rates of these proteins were proportional to their plasma concentrations. In glomerular haematurias, however, the ratios to albumin were much lower. The optimal discriminating ratio was found to be 2.0 x 10(-2) for alpha 2-macroglobulin/albumin and 2 x 10(-1) for IgG/albumin. Tubulointerstitial involvement in haematuria is characterized by elevated alpha 1-microglobulin excretion rates, with alpha 2-macroglobulin/albumin ratios below 2.0 x 10(-2) and IgG/albumin ratios above 2 x 10(-1). The reported procedure allows the exclusion and differentiation of clinically relevant proteinurias and haematurias in a single urine specimen.

Adult↗
PubMed1991

Differentiation of hematuria by quantitative determination of urinary marker proteins.

Hematuria caused by prerenal, glomerular, postglomerular, and postrenal causes is usually differentiated by a number of noninvasive and invasive diagnostic procedures. In the present study we have applied a new analytical strategy based on observations that the various forms of hematuria can be classified by their typical protein pattern. When analyzed by quantitative turbidimetric assays, urines from postrenal hematurias contained high-molecular-weight proteins (alpha 2-macroglobulin and IgG) in proportions found in plasma. Relating excretion rates (mg/mg) of these proteins to those of albumin, ratios for alpha 2-macroglobulin/albumin and IgG/albumin were 2.0-31 x 10(-2) and 20.0-180 x 10(-2), respectively. In contrast, glomerular hematurias exhibited ratios of 0.01-2.0 x 10(-2) (alpha 2-macroglobulin/albumin) and 2.0-20 x 10(-2) (IgG/albumin). Additional determination of alpha 1-microglobulin allowed us to differentiate postglomerular hematurias caused by interstitial nephropathies from glomerular and postrenal diseases. Critical evaluation of 93 cases diagnosed by independent clinical examination including histology, sonography, and cystoscopy revealed that the criteria derived from protein measurements resulted in correct classification when urine albumin exceeds 100 mg/l. This noninvasive procedure is expected to be of considerable help in the primary care of patients with unexplained hematuria.

Adolescent↗
PubMed1991

Mechanized toxicological serum tests in screening hospitalized patients.

A spectrum of quantitative and qualitative methods was adapted to the RA-1000/RA-XT selective analyser for the purpose of excluding or detecting common types of intoxication in the emergency laboratory of our primary care community hospital. Ethanol and salicylates (measured photometrically) and acetaminophen (measured immunologically by EMIT tox) were quantitatively analysed in serum. immunological group tests (EMIT tox) for barbiturates, benzodiazepines, tricyclic antidepressants and related compounds were used for qualitative analysis. Well established clinical chemical methods (aspartarte aminotransferase, alanine aminotransferase, creatine kinase, pseudocholinesterase, glucose and lactate) were applied to the serum samples using the same selective analyser. Within and between run precision, accuracy, recovery and detection ranges (linearity) fulfilled the recommendations of forefield toxicological analysis for all methods. Ethanol (g/l), measured photometrically with the RA-1000 analyser, agreed with the reference method (headspace gas-chromatography) with a correlation coefficient greater than 0.99 (y = 0.06 + 0.98x). Acetaminophen and salicylates showed correlation coefficients greater than 0.94 and greater than 0.99, when compared with manual colorimetric procedures (acetaminophen (mg/l): y = -3.22 + 0.896x; salicylates (mg/l): y = -2.1 + 1x). Qualitative group tests for barbiturates, benzodiazepines and tricyclic antidepressants measured with the RA-1000 analyser were in good agreement with the EMIT single test procedure. The ranges of the quantitative methods allowed quantification of analytes from therapeutic (non-toxic) to very high levels in undiluted samples (ethanol 0.05 up to 4 g/l; salicylates 32 up to 1200 mg/l and acetaminophen 1.9 up to 200 mg/l). The low detection limits of the qualitative tests allowed the recognition of compounds in plasma that were present in low concentrations and/or displayed only minor reactivity with the antibodies provided by the EMIT tox test kits. As a consequence, decision limits for all three group tests in serum were lowered to near the detection limit: (table: see text) For quantitative tests the lower limits of quantification were: (table: see text) The working reagents were stable for at least 14 days at 4-8 degrees C. Calibration curves were stable over the expiration period of reconstituted original reagents (6-12 weeks), also when working reagents were prepared in aliquots from stored reconstituted reagents. Application of the newly adapted programme to serum samples of nearly two hundred patients showed it to be suitable for screening patients in which intoxication is suspected or needs to be excluded.

Acetaminophen↗
PubMed1991

Overestimation of albumin in heparinized plasma.

Monochromatic measurement of albumin by the bromcresol green method leads to overestimation of albumin in the presence of heparin. The interference seems to be caused by fibrinogen, which, in the presence of heparin, produces an almost constant increase of the measuring signal over the whole range of suitable wavelengths (550 to 700 nm). The albumin overestimation can be eliminated by using a bichromatic modification. An application of this procedure for the automated analyzer RAXT, RA-1000 (Bayer Diagnostik, Technicon) is presented. We recommend using only bichromatic methods for albumin determination with bromcresol green to avoid unexpected analytical artifacts.

Bromcresol Green↗
PubMed1990

Regulation and localization of organic osmolytes in mammalian kidney.

Four organic small molecules belonging to the chemical groups of trimethylamines (betaine and glycerophosphorylcholine) and polyols (sorbitol and inositol) have been shown to act as organic osmolytes in the kidney. When measured along the corticopapillary axis, each exhibits a specific distribution pattern, indicating a specific localization and function. Studying their behaviour under vasopressin treatment in diabetes insipidus rats and after insulin treatment in diabetes mellitus rats confirmed this conclusion: AVP led to a steady increase of sorbitol and glycerophosphorylcholine over 7 days with no effect on inositol levels. Insulin treatment of diabetic rats, on the other hand, decreased sorbitol with a concomitant increase in glycerophosphorylcholine, again without any effect on tubular inositol concentrations. From this and in vitro studies it can be concluded that both hormones act by indirect mechanisms which alter interstitial osmolality. This in turn leads to a change in tubular osmolyte synthesis, uptake and release rates. In addition, the concentrations of the respective precursors glucose and choline influence the formation rates of sorbitol and betaine.

Animals↗
PubMed1990

Polyol determination along the rat nephron.

The polyols sorbitol and inositol were determined in single freshly microdissected tubule segments of rat kidney. Twenty different structures were separated from six different kidney zones reaching from cortex to papillary tip. Picomol amounts of sorbitol and inositol were quantitated by use of an enzymatic bioluminescence procedure. Experimental conditions (700 mosmol/kg, 4 degrees C) were chosen to assure constant polyol concentrations over 3 h dissection period. Sorbitol exhibited a concentration gradient in the collecting duct system from the outer/inner medullary border (3.9 +/- 0.5 pmol/mm) to the papillary tip (78.8 +/- 6.9 pmol/mm). In the same region descending and ascending limbs of Henle's loop contained 1.5 +/- 0.5 to 5.3 +/- 1.6 pmol/mm and 2.5 +/- 0.8 to 8.35 +/- 1.5 pmol/mm, respectively. In contrast, all outer medullary and cortical structures had lower sorbitol concentrations. Inositol amounts increased continuously in the collecting duct from cortex (5.3 +/- 0.5 pmol/mm) to inner medulla (30.7 +/- 3.8 pmol/mm). This polyol was also found in thick ascending limb of Henle's loop (6.2 +/- 1.1 pmol/mm in cortex to 11.2 +/- 1.4 pmol/mm in outer medulla) and in proximal tubules (5.6 +/- 1.2 pmol/mm in S1 and 4.5 +/- 1.5 pmol/mm in S3). When related to cellular volume measured by planimetry, intracellular sorbitol concentration was calculated to be 51 mmol/l in papillary collecting duct and inositol 28 mmol/l in outer medullary thick ascending limb cells. These data confirm the role of sorbitol in the renal concentrating process in papilla. Inositol seems to have additional function in thick ascending limb of Henle's loop and the proximal tubule.

Animals↗
PubMed1990

The role of the kidney in carnitine metabolism.

The kidney plays a major role in carnitine biosynthesis, excretion and acylation. Unlike in the rat, human kidney contains all enzymes needed to form carnitine from trimethyllysine in activities exceeding those of the liver. This carnitine precursor is found to be increased in plasma of patients with chronic renal failure. Free carnitine formed in the kidney as well as carnitine reabsorbed from the glomerular filtrate may be acylated in the proximal tubule. Isolated rat cortical tubule suspensions contain total carnitine concentrations of 2.85 mumols/g protein. During incubation over 60 min the acylcarnitine/carnitine ratio decreased, indicating deacylation of acylcarnitine in proximal tubules. Exogenous carnitine was acylated at a rate of 35 mumols/h.g protein. Besides pyruvate and acetate, ketone bodies stimulated the acylation rate severalfold, indicating that these substrates are a major source of acetyl-CoA for the acylation reaction. This may explain the higher acetylcarnitine/carnitine ratio found in urine under ketotic conditions.

Animals↗