Search PubMed⌕ Search

Biomedical subjects

J Kipnowski

Publications and source records attributed to J Kipnowski.

36 records · Page 2Linked to original sources
PubMed1983

Interaction of bemetizide and indomethacin in the kidney.

The effect of a single oral dose of 25 mg bemetizide on renal function without and with concomitant administration of the prostaglandin synthesis inhibitor indomethacin was investigated in ten healthy volunteers during sustained water diuresis. Bemetizide induced a significant increase in urinary sodium and chloride excretion from 196 +/- 30 and 163 +/- 28 mumol/min to 690 +/- 54 and 537 +/- 51 mumol/min (P less than 0.01). This effect occurred in the absence of changes in glomerular filtration rate, urinary excretion of phosphate or the delivery of chloride beyond the proximal nephron to the distal tubules (distal delivery) [(CH2O + CCl)/GFR . 100], but was associated with a significant decrease in distal fractional chloride absorption (DFACl) [CH2O/(CH2O + CCl)] from 0.84 +/- 0.02 to 0.63 +/- 0.02 (P less than 0.01). Bemetizide also increased urinary excretion of prostaglandin (PG) E2. Concomitant indomethacin administration significantly suppressed urinary excretion of PGE2 and markedly decreased urinary excretion of sodium and chloride during control and following bemetizide administration. Indomethacin had no effect on glomerular filtration rate, urinary excretion of phosphate, distal delivery or the urinary excretion of bemetizide but significantly increased DFACl both during control and after bemetizide administration. Our results show that bemetizide as a thiazide-diuretic acts in the diluting segments of the nephron. Indomethacin administration induces retention of sodium and chloride and blunts the renal effects of bemetizide via increased absorption in the diluting segments. The interaction of both drugs most likely represents a pharmacodynamic interaction.

Adult↗
PubMed1983

Role of carboxyl group in Na+-entry step at apical membrane of toad urinary bladder.

Mucosal addition of N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) and some lipid-soluble carbodiimides, agents which are selective for carboxyl groups, irreversibly inhibited Na+ transport as measured by short-circuit current (SCC) in the urinary bladder of the toad. The inhibition of Na+ transport by EEDQ had the following characteristics: 1) the inhibition was accompanied by a significant increase in the transepithelial electrical resistance; 2) the decrease in SCC was accounted for by a comparable decrease in 22Na+ influx without effect on Na+ efflux; 3) amphotericin B produced complete recovery of SCC inhibited with EEDQ but not with antimycin A or ouabain; 4) mucosal EEDQ decreased the amiloride-sensitive reversal of Na+ current that is induced by serosal nystatin in the absence of mucosal Na+; 5) vasopressin and acid mucosal pH caused an increase in SCC in proportion to the SCC remaining after EEDQ inhibition; and 6) Vmax of the SCC was decreased without alteration in the apparent Km for Na+. Based on these characteristics of EEDQ inhibition of Na+ transport, we infer that a carboxyl group of the Na+ channel is involved in the Na+-entry step across the apical membrane of "tight" epithelia. The inhibition of Na+ transport with EEDQ most likely involves closing the Na+ channel through a chemical reaction involving a carboxyl group of the channel.

Adrenergic alpha-Antagonists↗
PubMed1983

Modification of carboxyl of Na+ channel inhibits aldosterone action on Na+ transport.

We investigated the effect of the carboxyl-selective reagent N-ethoxycarbonyl-2-ethoxy-1,2-dihydroquinoline (EEDQ) on aldosterone stimulation of Na+ transport in the urinary bladder of the toad. Na+ transport, measured as the short-circuit current (SCC), was irreversibly inhibited by EEDQ in a dose- and time-dependent manner prior to addition of aldosterone. The greater the percentage inhibition by EEDQ (X), the smaller was the maximal increase of SCC after aldosterone (Y). This relationship gave the regression equation Y = 128.41 - 1.73X, r = -0.99 (n = 35). Evidence that the inhibition of SCC produced by EEDQ was limited to effects at the mucosal membrane was attested by the following: 1) EEDQ did not alter the stimulation by aldosterone of the osmotic water flow response to antidiuretic hormone; 2) whereas inhibition of protein synthesis by cycloheximide prevented this effect of aldosterone; 3) amphotericin B fully restored SCC previously inhibited by EEDQ to the level produced in tissues not inhibited by EEDQ; 4) comparison of the effects of amiloride vs. EEDQ pretreatment on the SCC response to aldosterone and amphotericin B revealed nearly identical characteristics; 5) in contrast, amphotericin B stimulation of SCC was limited when Na+ transport was limited by antimycin A (an inhibitor of energy production) or by ouabain. The findings fail to provide positive evidence for the hypothesis that aldosterone induces the synthesis of new Na+ channels but are consistent with hormonal activation of previously existing but nonfunctioning Na+ channels.

Adrenergic beta-Antagonists↗
PubMed1982

Molecular action of aldosterone.

Aldosterone stimulates the reabsorption of sodium across epithelial cells of various target tissues. The initial events in the molecular action of the mineralocorticoid are the following: (1) Diffusion of the steroid across the cellular (baso-lateral, serosal) plasma membrane into the cytoplasmic compartment. (2) Binding of the steroid to a receptor protein specific for the class of steroid and activation of this steroid-receptor-complex. (3) Translocation of the activated aldosterone-receptor complex to the nucleus and stimulation of RNA synthesis (including the synthesis of messenger RNA and ribosomal RNA). (4) Translation of the steroid-induced messenger RNAs at the ribosomal level into the aldosterone-induced proteins (AIP) within the cytoplasmic compartment. Whereas these induction steps are uniformly accepted, the mechanisms by which the AIPs increase the activity of a rate-limiting step in the sodium transport process are still object of debate. In this paper we discuss the initial events in the mode of action of aldosterone and the biochemical and physiological approaches to the aldosterone-induced proteins with special reference to the "sodium permease", the "energy", and the "sodium pump" theory. Our analysis shows that despite serious efforts by multiple laboratories, the first AIP with an established relationship to the mineralocorticoid actions of aldosterone is yet to be identified.

Aldosterone↗
PubMed1982

[Suppressive treatment of normothyroid female goitre patients with reference to patient compliance (author's transl)].

Synthetic L-thyroxine (100-150 micrograms/d) was administered for 18 months to 110 female patients with normothyroid diffuse goitre size II. Reduction of size was observed in 60 patients after one year, in a further 10 there was no increase in size. Increase of neck circumference and thyroid gland size in 40 patients could be explained by patient non-compliance in 35 females. Renewed assessment of treatment results after another 6 months showed decrease of neck circumference and thyroid gland size in 98 out of the 110 patients. There were no significant differences among in vitro parameters (total thyroxine, normalisation of thyroxine ratio and triiodothyronine) assessed at 12 and 18 months among patients treated successfully and without success. However, the TRH test for delta TSH (TSH stim-TSH basal) showed significantly higher values after 12 months in the non-compliant group treated without success initially. These differences could not be demonstrated after 18 months. The results show that consideration of compliance behaviour in conjunction with the intravenous TRH test clearly improve results of conservative treatment of normothyroid diffuse goitre.

Adult↗
PubMed1982

Prostaglandins participate in the regulation of NaCl absorption in the diluting segments of the nephron in vivo: effects of furosemide.

Various studies point to a role of the renal prostaglandin (PG) system in the regulation of renal NaCl excretion. In the present experiments, distal delivery of proximal tubular fluid (DD) [CH20 + CC1)/GFR x 100] and distal fractional chloride absorption (DFAC1) [CH20/(CH20 + CC1)] were studied in 6 healthy volunteers undergoing sustained water diuresis. Studies of renal function were performed during intravenous infusion of hypotonic (0.45%) saline and during additional treatment with indomethacin, furosemide and furosemide plus indomethacin. Hypotonic saline was infused at increasing rates of 0.09, 0.18, and 0.36 ml min-1 kg-1 body weight each for a 45-min period. DD over all three clearance periods averaged 8.27 +/- 0.71 ml min-1 100 ml-1 glomerular filtration rate (GFR) during saline infusion alone and was unchanged by indomethacin (8.09 +/- 0.63 ml min-1 100 ml-1 GFR). DFAC1 averaged 0.79 +/- 0.02 during saline and significantly increased to 0.87 +/- 0.01 (p less than 0.002) during concomitant indomethacin treatment. Increased NaCl absorption in the diluting segment during indomethacin was paralleled by a decrease in urinary excretion of chloride (UC1V) from 221 +/- 29 during control to 124 +/- 19 muEq/min (p less than 0.025) and in urinary excretion of PGE2 (UPGE2V) from 1.45 +/- 0.12 to 0.51 +/- 0.09 pmol/min (p less than 0.025). Furosemide increased UPGE2V to 2.94 +/- 0.34 pmol/min (p less than 0.05) and UC1V to 2,590 +/- 128 muEq/min (p less than 0.001). This effect was associated with an increase in DD to 26.70 +/- 1.33 ml min-1 100 ml-1 GFR (p less than 0.001) and a decrease in DFAC1 to 0.19 +/- 0.02 (p less than 0.001). Neither DD and DFAC1 nor UC1V were altered during furosemide+indomethacin as compared to furosemide in spite of a marked suppression of UPGE2V to 0.56 +/- 0.13 pmol/min. Our results support the concept that renal PG participate in the regulation of NaCl absorption in the diluting segments of the nephron. Furthermore, the tubular effects of furosemide appear not to be mediated by the PG system.

Absorption↗
PubMed1981

[Hepato-renal syndrome (author's transl)].

The hepato-renal syndrome is defined as potentially reversible functional renal failure associated with acute fulminant hepatitis or, more often, with advanced chronic liver failure. It is characterized by oliguria, azotemia, retention of sodium and water with formation of ascites, and hyponatremia. While urinary sodium concentration of less than 10 mEq/l reflects intact tubular sodium absorption, the kidney lacks the ability for adequate free-water generation. This condition must be separated from specific renal diseases which may arise during the course of intra-or extrahepatic diseases and which must be classified accordingly. Pathophysiological aspects of the hepa-to-renal syndrome include hemodynamic factors, such as changes in intrarenal blood flow distribution in the presence of elevated intrarenal and reduced peripheral vascular resistance. The functional relationship of vasoconstrictor, sodium retaining, and anti-diuretic hormones (e.g., renin-angiotensin, aldosterone, and vasopressin) to vasodilator, diuretic, and natriuretic hormonal factors (e.g., prostaglandins, kinins, and natriuretic hormone) may be altered as well. Finally, a pre- and intrahepatic spillover resulting in decreased endotoxin clearance must be considered. Due to the lack of understanding of their complex interactions, so far pharmacological and therapeutic approaches remained ineffective to correct at least some of these factors. Today, recovery from hepato-renal syndrome will, therefore, mainly depend on the course of the underlying liver disease.

Acute Kidney Injury↗
PubMed1980

[Hormone picture in female patients with diffuse and nodular goiter].

Concentration of total thyroxine, normalized thyroxine ratio, T3-RIA, and Serum TSH before and 30 minutes after stimulation with 0,2 mg TRH i.v. in various forms of euthyroid goiter were determined. There were no significant differences between the three clinical groups of goiter patients. We draw the conclusion that the dependence on TSH, as one important factor in pathogenesis, can on the one hand lead to a diffuse goiter and, on the other hand lead to a nodous goiter. That means, that different developments of goiter are determined by specific thyroid tissue factors.

Adult↗
PubMed1980

Immunoreactive substance P in human plasma: response to changes in posture and sodium balance.

1. In healthy volunteers plasma concentrations of immunoreactive substance P were measured in response to changes in posture and dietary salt intake. 2. In 14 subjects plasma immunoreactive substance P was 168 +/- 31 pmol/l when subjects were supine and 401 +/- 51 pmol/l (P less than 0.001) when they were ambulant. 3. Measurement of supine plasma immunoreactive substance P at 6 h intervals gave a mean value of 240 +/- 39 pmol/l at 14.00 hours and a lowest value of 76 +/- 9 pmol/l at 02.00 hours. 4. In eight healthy subjects plasma immunoreactive substance P rose only slightly from 169 +/0 41 pmol/l, on a sodium intake ad lib., to 244 +/- 45 pmol/l by day 4 of dietary sodium restriction (35 mmol/day) and significantly fell to 51 +/- 20 pmol/l (P less than 0.001) by day 4 of high sodium intake (350 mmol/day). 5. Although exogenous substance P was shown to be natriuretic in dog and rat, the present results do not favour a role of endogenous substance P as a circulating natriuretic factor in man.

Adult↗
PubMedDate not supplied

[Psychosomatic contribution to the etiopathogenesis of colitis ulcerosa].

In the present investigation biographic and test-psychologically collected variables in patients with chronically recurrent and chronically continuous forms of colitis ulcerosa are described and analysed. While in patients with a chronically recurrent course of the disease coincident reactions upon situations and/or constellations of situations considered as encumbrance or stress in the sense of the onset of the disease or its recurrence could be discovered, such correlations were found in less than 20 per cent of the patients with a primarily chronic course of the disease. In the latter patients, however the "psychosomatic phenomenon" according to Stephanos [16] could be observed. An analysis of both groups of patients revealed a high correlation between the factors course of the disease and alexithymic characteristics.

Adolescent↗
PubMedDate not supplied

Decreased gastric prostaglandin E2 synthesis in patients with gastric ulcers and in smokers.

BACKGROUND/AIMS: Prostaglandin inhibits gastric acid secretion and exerts protective action on the mucosa of the stomach. We studied the synthesis of prostaglandin E2 (PGE2) to determine the role of PGE2 in peptic ulcer disease. MATERIALS AND METHODS: Mucosal biopsies from 22 persons were obtained and incubated. PGE2 was then determined by radioimmunoassay. RESULTS: Compared to healthy subjects, patients with gastric ulcers or gastritis show diminished accumulation of PGE2 in the incubation medium. Other factors like age, gender, and alcohol consumption were also investigated, however, they do not influence endogenous prostaglandin production. In contrast, PGE2 synthesis was found to be decreased in smokers. CONCLUSIONS: Our data indicates a deficiency in endogenous PGE2 synthesis as one cause of gastric ulcerations and offer an explanation of the higher incidence of gastric ulcer disease in subjects with nicotine abuse.

Adult↗
PubMedDate not supplied

Alteration of prostaglandin E2 and leukotriene B4 synthesis in chronic inflammatory bowel disease.

BACKGROUND: Eicosanoid mediators play an important role in the pathogenesis of chronic inflammatory bowel disease. MATERIALS AND METHODS: The synthesis of prostaglandin E2 and leukotriene B4 in biopsied colonic specimens from patients with inflammatory bowel disease was compared with that from healthy controls. In contrast to surgical resection, biopsy by colonoscopy enabled patients with milder disease to be investigated. RESULTS: In subjects with Crohn's disease or ulcerative colitis, the synthesis of PGE2 was significantly (p < 0.05) increased, whereas synthesis of LTB4 remained unaltered. In addition, no differences in PGE2 and LTB4 production were found in different age groups or sex. CONCLUSION: We conclude that prostaglandin E2, compared to leukotriene B4, is the dominant eicosanoid in moderate inflammatory bowel disease.

Adult↗
PubMedDate not supplied

Calcium modulates the synthesis of prostaglandin E2 in isolated colonic mucosal cells.

BACKGROUND/AIMS: The effect of calcium on colonic prostaglandin E2 synthesis was investigated in 26 healthy volunteers. MATERIAL AND METHODS: Biopsy specimens were obtained by colonoscopy and the mucosal cells were separated biochemically. The cells were incubated in EDTA or CaCl2 containing media for 15 and 30 minutes. RESULTS: The PGE2 synthesis was significantly (p < 0.001) diminished in the calcium free suspension (EDTA) compared to the CaCl2 containing suspension. To increase intracellular Ca2+ concentration, calcium ionophore A 23187 was added for the last 15 minutes. It significantly stimulated the prostaglandin production. In addition, the calcium channel blocker verapamil did not alter the PGE2 synthesis, whereas trifluoperazine, a calmodulin inhibitor, markedly decreased the production rate. CONCLUSION: Calcium is an important stimulus of prostaglandin synthesis and inhibition of calmodulin by trifluoperazine decreases the arachidonic metabolism. In these regards, colonic tissue shares features with other tissues. However, in contrast to smooth or cardiac muscle, intracellular calcium concentration in colonic mucosa is not affected by verapamil, indicating that colonic calcium channels have a different affinity to this drug.

Adult↗
PubMedDate not supplied

Magaldrate stimulates endogenous prostaglandin E2 synthesis in human gastric mucosa in vitro and in vivo.

BACKGROUND/AIMS: Prostaglandin E2 (PGE2) plays an important role in the inhibition of gastric acid production and exerts cytoprotective action. The in vitro and in vivo effect of magaldrate, an aluminum containing antacid, on PGE2 synthesis in the gastric mucosa was investigated. METHODOLOGY: In the first part of the study, magaldrate was added to a suspension of isolated gastric mucosal cells. In the second part, the antacid gel was applied to the gastric mucosa during gastroscopy and biopsies were taken from the same site 5 and 10 min later. RESULTS: The antacid significantly stimulated PGE2 release from the suspension of isolated gastric cells in vitro. The biopsies obtained after the application of magaldrate showed an increased PGE2 production compared to specimens obtained before. CONCLUSIONS: The data suggest that in addition to its neutralizing capacity as an antacid, magaldrate contributes to the cytoprotective activity of the mucosa by stimulating endogenous PGE2 synthesis.

Adult↗