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Biomedical subjects

M Schmolke

Publications and source records attributed to M Schmolke.

At least 37 records · Page 2Linked to original sources
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↗
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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1989

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↗
PubMed1986

[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↗
PubMed1985

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↗
PubMed1984

Effects of nicotine on epithelial nephron cells in culture.

Long-term effects of nicotine on cultured cells derived from defined segments of the nephron were studied in vitro. Nicotine was added during a 10-day incubation period to a defined nephron culture medium (NCM) which had been supplemented with one of the following: fetal calf serum (FCS), dexamethasone (D), aldosterone (A), or epidermal growth factor (EGF). Thymidine incorporation (10(-15) mmol/10(3) cells) into cultured cells of the cortical thick ascending loop of Henle (TAL) and of the cortical collecting tubule (CT) was inhibited by nicotine (5 X 10(1) ng/ml) when incubated in NCM only; the presence of FCS or of D (10(-8) M) or of D and EGF (25 ng/ml) prevented this inhibitory effect. Nicotine at a concentration of 5 X 10(2) ng/ml was inhibitory in TAL and CT even in the presence of FCS. Na-K-ATPase activity (pmol/10(3) cells X min-1) was stimulated significantly by D when compared with NCM; nicotine (5 X 10(2) ng/ml) prevented this inductive effect. Transepithelial voltage was 27.1 +/- 6 (mV) after incubation with A (10(-9) M), and 7.2 +/- 4.1 when incubated with A and nicotine (5 X 10(2) ng/ml). These data indicate that nicotine may interfere with factors stimulating cell proliferation, sodium pump enzyme activity, and ion flux (voltage). An effect of nicotine on the cellular Na-entry step would be consistent with the data.

Animals↗
PubMed1976

[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↗