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Biomedical subjects

M Schmolke

Publications and source records attributed to M Schmolke.

At least 19 recordsLinked to original sources

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

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

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

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

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

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

Regulation of organic osmolyte concentrations in tubules from rat renal inner medulla.

Glycerophosphorylcholine, inositol, and sorbitol were measured in rat kidney homogenates and tubules from inner medulla and papilla by enzymatic spectrophotometric techniques. Organic osmolytes exhibited their highest concentrations in the papillary tip. In contrast to glycerophosphorylcholine and sorbitol, inositol was of similar high concentrations in inner and outer medulla. Freshly prepared inner medullary tubules maintained tissue osmolyte concentrations under control, antidiuretic, and furosemide diuretic conditions. When tubules were incubated in vitro over 90 min, tubular organic osmolyte concentrations decreased as a function of extracellular NaCl, but not urea concentrations. Organic osmolyte disappearance from cells was quantitatively recovered from the medium. In contrast, medium lactate dehydrogenase activity did not rise in parallel and tubular ATP remained constant. Glucose up to a concentration of 200 mM increased tubule and medium sorbitol. The results obtained indicate that glycerophosphorylcholine, sorbitol, and inositol rapidly adapt their intracellular concentrations to extracellular NaCl osmolality by a change in tubular plasma membrane permeability. In addition sorbitol levels are regulated by the extracellular glucose concentration.

Animals

Effect of antidiuretic hormone on renal organic osmolytes in Brattleboro rats.

Homozygous Brattleboro rats were used to study the effect of antidiuretic hormone (ADH) on organic osmolytes, which have been shown to be involved in the cellular osmoadaptation in renal inner medulla. With the use of enzymatic spectrophotometric methods, glycerophosphorylcholine, sorbitol, and inositol were determined in kidney sections from papillary tip (IM3) to cortex. Compared with normal rat kidneys, IM3 of untreated Brattleboro rats (urine osmolality 132 mosmol/kg) were sorbitol depleted (16 +/- 1 vs. 371 +/- 37 mumol/g protein) and glycerophosphorylcholine was reduced to 20% (131 +/- 16 vs. 658 +/- 52 mumol/g protein). In contrast inositol was not changed (147 +/- 25 vs. 177 +/- 29 mumol/g protein). Similar effects were obtained in all medullary sections. Continuous treatment with ADH increased urine osmolality already after 5 h but renal glycerophosphorylcholine and sorbitol content only after 24 h. Normal osmolyte levels were reached after 3 days of ADH treatment when urine osmolality was 1,595 mosmol/kg. Inositol did not exhibit comparable changes during ADH treatment. The present results indicate that ADH, possibly by increasing interstitial tonicity, leads to increased glycerophosphorylcholine and sorbitol, but not inositol, contents.

Animals

Expression of sodium pump activity and of transepithelial voltage induced by hormones in cultured cortical collecting tubule cells.

Primary monolayer cultures of polarized epithelia were derived from single cortical collecting tubules (CCT) of the mammalian kidney (rabbit). The expression of Na-K-ATPase activity (mol 10(-15)/min.cell) and of the transepithelial voltage (VT) in monolayers on membranes was measured in response to defined hormonal supplements of the nephron culture medium (NCM). Hormones were: triiodothyronine (T3; 10(-11) M), dexamethasone (10(-8) M), and aldosterone (10(-9) M). Control was NCM plus fetal calf serum (FCS; 3% v/v). Data are mean (SEM). Na-K-ATPase activity was 10.4 (6.2) in control (n = 27); 18.8 (5.2) in T3 (n = 35); 21.2 (5.5) in dexamethasone (n = 26), and 30.9 (6.5) in aldosterone (n = 24). VT (mV) was 4.2 (3.2) in control (n = 12); 12.7 (3.7) in T3 (n = 12); 16.8 (2.5) in dexamethasone (n = 12), and 28.4 (3.6) in aldosterone (n = 14). Data are evidence that thyroid and corticosteroid hormones selectively induce the postmitotic expression of the sodium carrier activity and other functions related to vectorial solute transport in this polarized epithelium.

Aldosterone

[Preventive and simultaneous appendectomy].

75 patients underwent simultaneous appendectomy, when gall bladder, stomach or large bowel were chiefly operated. Complications of incision marks were observed in six cases, but only one of them being possibly due to appendectomy. Six common complications could not be explained by additional operation. Postoperative treatment was not extended. 5 patients died due to the severity of their main disease. Prophylactic or simultaneous appendectomy were conditionally recommended and subjected to a decision by a fully experienced surgeon.

Appendectomy

The study of epithelial function by in vitro culture of nephron cells.

Cultured nephron epithelia offer an advantage as they are available in a completely controlled monolayer environment. Some of the culture systems retain differentiated properties for a time span sufficient to study long term chemical and physical events in epithelia of defined nephronal origin. The characteristics expressed in culture include transepithelial voltage and resistance in cells derived from distal nephron segments, and the hormonal dependence of these parameters. Na-K-ATPase activity and its selective regulation by steroid and thyroid hormones has been evaluated in defined epithelial monolayers. Further, the acute stimulation of adenylate cyclase activity has been demonstrated in human nephron culture, and the Na-coupled glucose transport is present in cortical cell cultures. Transepithelial voltage and Na-K-ATPase activity may be considered complex and highly differentiated expressions of function as they are indicative of several apical and basal transporter systems in cultured polarized nephron cells. The intention of current work is to establish functional lines from defined segments of the nephron, using strategies of passage, cloning, and transfection.

Animals

[Peculiarities of acute appendicitis in women].

A complete documentation of the clinical and operative findings and a comparison of these with the histologic diagnosis in nearly 900 appendectomy patients from a period of more than two years is presented. In this publication an account of the specific results of nearly 500 women is given. The influences of age, menstruation, and gynecologic illnesses are reported in detail. Sixty-five percent of all women were treated unnecessarily with appendectomy. However, the indications for this operation should not be limited on these grounds.

Acute Disease