[Clinical importance of the Na+/H(+) antiporter].
Explore the source record for details and available documents.
Carrier Proteins↗
Biomedical subjects
G Hoffmann
Publications and source records attributed to G Hoffmann.
Citrate and recurrent idiopathic calcium urolithiasis. A longitudinal pilot study on the metabolic effects of oral potassium sodium citrate administered as short-, medium- and long-term to male stone patients.
In male patients with idiopathic recurrent calcium urolithiasis (RCU) the effects of oral potassium sodium citrate (PSC) on acid-base, citrate and mineral metabolism were investigated. There were 17 normocitraturic and 15 hypocitraturic patients. The examination time points in our clinical laboratory were prior to medication and after 3, 6 and over 12 months of medication. Urine collection periods were over 24 h, 2 h--after an overnight fast--3 h postprandially. Acceptance by the patients was poor, a large number refusing to take PSC for 12 months. Compliance of the patients continuing with the study was adequate as assessed by the urinary excretion of potassium and sodium. No unwanted side effects were observed. After 3 months of PSC medication a compensated metabolic alkalosis developed; in the urine calcium was decreased, while citrate, pH and oxalate were increased, as were hydroxyapatite supersaturation and calcium phosphate particles. After more than 12 months of PSC medication, citrate and pH tended toward the pretreatment baseline values, while hydroxyapatite supersaturation and calcium had already returned to pretreatment values. Despite ongoing PSC intake, patients with pre-existing hypocitraturia had lower urinary citrate than patients with previous normocitraturia, while the concomitant pH and hydroxyapatite supersaturation in the urine of the former remained at levels close to those of the latter. Under the influence of PSC, parathyroid gland function remained unchanged, but serum levels of bone alkaline phosphatase and osteocalcin were low, and urinary hydroxyproline was high.(ABSTRACT TRUNCATED AT 250 WORDS)
Acid-Base Equilibrium↗
Dihydrospirorenone (ZK30595): a novel synthetic progestagen--characterization of binding to different receptor proteins.
Dihydrospirorenone (6 beta, 7 beta, 15 beta, 16 beta-dimethylen-3-oxo-17a-pregn-4-en-21, 17-carbolacton) is a new type of progestin with no other agonistic activities, in particular no estrogenic, androgenic or glucocorticoid activity. Dihydrospirorenone is a potent aldosterone antagonist 8 times as potent as spironolactone and antiandrogenic (0.3 times cyproterone acetate). The aim of the present study is to make a broad characterization of dihydrospirorenone at the receptor level and to discuss the results in comparison to those of established progestins. Kinetic studies of 3H-dihydrospirorenone uptake show a rapid increase in the amount of specific binding during the first three hours. The dissociation of 3H-dihydrospirorenone from the cytoplasmic human uterine progesterone receptor, measured by displacement of labeled steroid with dextran-coated charcoal treatment at 4 degrees C at various times, showed a monophasic or one-component, first order dissociation curve like progesterone. Sucrose density gradient centrifugation of the 3H-dihydrospirorenone-labeled myometrial cytosol showed that the dihydrospirorenone binding components sedimented in the 4S and 8S region which is typical for the progesterone receptor under low salt conditions. The high binding affinity of dihydrospirorenone to the binding sites of the mineralocorticoid receptor of rat kidney with an RBA value of 230% compared to aldosterone is remarkable. This reflects the strong antimineralocorticoid activity of this compound which was evaluated in adrenalectomized rats. Furthermore, competitive studies indicated that dihydrospirorenone also displays high affinity for the androgen and some affinity for the glucocorticoid receptors but no measurable affinity for the estrogen receptor.
Androstenes↗
Bioactive ergost-5-ene-3 beta, 7 alpha-diol derivatives from Pseudobersama mossambicensis.
Bioactivity-directed fractionation of the methyl ethyl ketone extract of Pseudobersama mossambicensis resulted in the isolation of ergosta-5,24(28)-diene-3 beta,7 alpha-diol [1], 24,28-epoxyergost-5-ene-3 beta,7 alpha-diol [2], and ergost-5-ene-3 beta,7 alpha,24,28-tetraol [3]. All three sterols showed selective activity towards DNA repair-deficient yeast mutants. The sterol 1 also showed cytotoxicity towards wild-type P-388 murine leukemia cells. The isolation, structural elucidation, and biological activities of these sterols are reported. The sterol 3 is most probably an artifact formed from 2 during the isolation process.
Animals↗
[Drug dependence, smoking and fetal growth retardation].
Illicit drug abuse, as well as smoking, are known risk factors in the development of intrauterine growth retardation. In an attempt to clarify the influence of these two aetiological factors, a retrospective analysis was carried out. 35 drug- and nicotine-addicted pregnant women were compared to 104 smokers and 101 non-smoking controls with regard to foetal outcome. Relative risk estimates for intrauterine growth retardation of the drug and nicotine group were 3.14 (95% confidence limits 1.88-5.25; p = 0.0001) whereas the smoking group had 1.39 (95% confidence limits 0.96-2.02; p = 0.0482) compared to non-smoking controls. The foetal outcome was best in the latter group: children of drug-addicted mothers had a considerably higher morbidity and mortality rate. This study shows an almost threefold risk for intrauterine growth retardation in drug-addicts who smoke, compared to nicotine abuse alone.
Acid-Base Equilibrium↗
Platelet cAMP and cGMP in essential hypertension.
Vasodilator substances released in the blood vessel wall, such as the endothelium-derived relaxing factor (EDRF) and prostacyclin (PGI2), may participate in the regulation of arterial blood pressure. However, their role in the pathogenesis of human essential hypertension to date remains unclear. For some of these factors affecting vascular smooth muscle cells, blood platelets represent a second target tissue. Thus, EDRF and PGI2 inactivate platelets by stimulation of cyclic guanosine-5'-monophosphate (cGMP) and cyclic adenosine-5'-monophosphate (cAMP) synthesis, respectively. In the present study, platelet cAMP (n = 68) and cGMP (n = 60) were determined in a control group of healthy subjects (C) and in 12 patients with untreated essential hypertension (EH). In the control group, platelet cAMP and cGMP content averaged 13.52 +/- 0.38 and 1.48 +/- 0.06 pmol/10(9) platelets and no dependence of either variable on sex or age could be established. Furthermore, cGMP levels were similar in EH as compared to the control group (1.38 +/- 0.11 pmol/10(9) platelets). However, intracellular concentrations of cAMP were significantly lower in EH as compared to C (11.22 +/- 1.37 pmol/10(9) platelets; P < .01). In addition, we investigated the stimulatory effect on cAMP of the stable PGI2 analog iloprost (10(-9), 5 x 10(-9), 10(-8), 5 x 10(-8) mol/L) in the platelets of 12 control subjects (C12) and EH.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
Role of endogenously released cholecystokinin in determining postprandial insulin levels in man: effects of loxiglumide, a specific cholecystokinin receptor antagonist.
To estimate the contribution of postprandial cholecystokinin (CCK) responses to circulating insulin concentrations and insulin secretion, a specific CCK receptor antagonist (loxiglumide; 10 mg/kg body weight/h) or saline were infused intravenously in normal volunteers, beginning 90 min before insulin secretion was stimulated on separate occasions by the intraduodenal administrations of glucose, glucose and protein, and glucose plus protein with the admixture of pancreatin. The release of CCK (radioimmunoassay) was stimulated by the protein component of the nutrients from basal 2.4 +/- 0.4 to 8.0 +/- 1.2 pmol/l. CCK plasma levels were significantly higher with loxiglumide (p < 0.05). Glucose-dependent insulinotropic polypeptide (GIP) was also released by all nutrient mixtures. Loxiglumide significantly inhibited the amount of bilirubin and pancreatic enzymes recovered from duodenal aspirates. In contrast, in none of the experiments, C-peptide increments and hence insulin secretion rates were altered by loxiglumide. With glucose and protein as intraduodenal stimulus (no pancreatin added), the plasma amino acids rose significantly less (by approximately 50% of the control experiment) and the increment in insulin (but not C-peptide) concentrations was significantly reduced by loxiglumide. This is most likely explained by a change in insulin metabolic clearance. This effect cannot be a primary action of CCK because there was no similar effect of loxiglumide with the same intraduodenal stimulus plus added pancreatin. Pancreatic enzymes reduced maldigestion secondary to loxiglumide effects on pancreatic exocrine secretion: The increment in circulating amino acid concentrations was similar with and without loxiglumide. In conclusion, CCK does not alter insulin secretion and, therefore, is not an incretin hormone in man. Blocking CCK actions on the exocrine pancreas by loxiglumide, however, can secondarily cause reductions in postprandial insulin profiles by altering insulin clearance. These changes are possibly related to reductions in circulating amino acid concentrations.
Adult↗
ACE-inhibition, kinins, and vascular PGI2 synthesis.
In the present studies, ex vivo-, in vitro-, and in vivo-effects of three structurally different angiotensin I-converting enzyme (ACE) inhibitors on the kallikrein-kinin and eicosanoid systems are described. In the ex vivo- and in vitro-experiments using isolated rat aorta, vascular prostacyclin (PGI2) production is dose-dependently stimulated by the ACE inhibitors captopril, lisinopril, and ramipril. Furthermore, the ACE inhibitor-induced augmentation of vascular PGI2 synthesis observed in vitro was completely inhibited by the competitive bradykinin antagonist D-Arg[Hyp3,Thi5,8,D-Phe7]bradykinin suggesting that ACE inhibitors stimulate PGI2 generation by an enhancement of kinin activity. In the in vivo studies in healthy volunteers, we used platelet cyclic adenosine-5'-monophosphate (cAMP) and cyclic guanosine-5'-monophosphate (cGMP) as indirect parameters of the activity of prostacyclin and the endothelium-derived relaxing factor, respectively. Since platelet cAMP and cGMP were unaffected by an acute dose of 10 mg of lisinopril, our data do not support the concept that the interference of ACE inhibitors with the kallikrein-kinin-prostaglandin system observed ex vivo and in vitro participates in the haemodynamic effects of these agents in humans in vivo.
Angiotensin-Converting Enzyme Inhibitors↗
[The relationships between the internal and external pelvic measurements of Schwartzbunt cows].
1118 Friesian cows and 101 Friesian heifers were investigated in internal pelvic measurements and their relationships to external measurements. The mean of the pelvic vertical and the medium diagonally diameter of the pelvis are 19.8 cm and 18.3 cm. 363.9 square centimetres and 76.3 centimetres were found for the pelvic surface and pelvic circumference. The difference between the biggest and smallest pelvis was 295.0 square centimetres. Medium to high coefficiences of correlation were detected between the internal pelvic measurements but relationships between internal and external pelvic measurements were low. From determined external pelvic measurements only the hip breadth provides usefull informations of the pelvic shape.
Animals↗
Treatment of endometriosis with leuprorelin acetate depot: a German multicentre study.
During the past decade, the development of various gonadotrophin-releasing hormone (Gn-RH) agonists, which induce reversible hypo-oestrogenism has opened a new area in the medical management of endometriosis. In an open, multicentre phase III study, the efficacy, tolerance and safety of the Gn-RH agonist leuprorelin acetate were tested. The preliminary results of 104 women treated in seven German centres are presented. Pelvic endometriosis was diagnosed by laparoscopy and classified according to the American Fertility Society scoring system: 33% of patients had minimal, 22% mild, 28% moderate and 8% severe endometriosis and in 9% no pathological results were obtained. The patients' mean age was 30 +/- 6 years and 66 had infertility problems. Treatment was started within the first 3 days of the menstrual cycle and consisted of a subcutaneous injection of leuprorelin acetate 3.75 mg, repeated once monthly over 24 weeks. A follow-up period of 12 months after the last injection has been completed in 70 patients, including a second laparoscopy. At all visits, symptoms were evaluated, physical examinations performed, and blood samples collected for haematological screening, serum chemistry determinations and measurement of the gonadotrophins oestradiol and progesterone and leuprorelin acetate. The median score at laparoscopy fell from 12 before operation to 8 after operation and 2 after treatment with leuprorelin acetate. Of the total number of patients, 89% had improvements in their endometriosis, 8% a deterioration and 3% no change. Patients reported improvement in the following: dysmenorrhoea 93%, dyspareunia 62% and pelvic pain 70%. However, all women complained of at least one of the following symptoms: hot flushes 86%, sleep disturbance 62%, sweating 61%, headache 41%, nausea 32% and depression 20%. Fifty-five percent of patients reported additional side effects such as vaginal dryness, fatigue and lower abdominal pain. After the third injection, amenorrhoea persisted in 94% of the women. Four weeks after the first leuprorelin acetate injection median concentrations of oestradiol fell from 45 pg/ml to 11 pg/ml, follicle-stimulating hormone from 7 U/L to 3 U/L and luteinising hormone from 5 U/L to 1 U/L and remained almost unchanged over the observation period. During the 6 months' treatment, laboratory parameters showed no significant deviations from normal; only total cholesterol, high-density lipoprotein cholesterol and alkaline phosphatase increased. Treatment results were judged as good and satisfactory in 82% and 11% of cases, respectively. On the basis of this study, it can be concluded that leuprorelin acetate treatment is safe, well tolerated and effective in the medical management of endometriosis and endometriosis-related complaints.
Adult↗
[Diagnostic and therapeutic strategies in locally recurrent rectal cancer].
Following curative operation for rectal cancer, 14-44% of the patients develop a local recurrence, in most instances situated in the operative bed. Differentiation of recurrent tumor, scar tissue and inflammation is not always possible by computerized tomography and magnetic resonance imaging. Recurrent tumor in these patients is diagnosed by percutaneous biopsy and histological analysis. In 24 patients in whom operation was impossible and a maximum irradiation dose was also applied, chemotherapy was administered in the form of regional perfusions. The internal iliac arteries were perfused with folinic acid and 5-fluorouracil in these patients. This procedure reduced the intensity of pain or achieved a pain-free interval of 9 days to 8 months.
Chemoembolization, Therapeutic↗
Significant correlations between atmospheric spectra according to Baumer and the in vitro incorporation of [3H]thymidine into the nuclear DNA of C6-glioma cells.
Significant correlations between certain spectra of atmospherics (spherics) according to Baumer (a.t.B), i.e. naturally occurring electro-magnetic impulses in the range of 4-50 kHz, and several diseases or biological parameters have been published earlier. Now we show that there exists a highly significant negative correlation (r = -0.61, P greater than 0.004) between the occurrence of 28 kHz impulses (a.t.B.) and the in vitro incorporation of thymidine into the nuclear DNA of C6-glioma cells. The positive correlation with the 10 kHz impulses (a.t.B) (r = 0.39), however, is statistically not significant (P greater than 0.055).
Animals↗
Significant correlations between certain spectra of atmospherics and different biological and pathological parameters.
Atmospherics are very short naturally occurring electromagnetic impulses of between 4 and 50 kHz. In this review we summarize our results concerning the correlations between certain spectra of atmospherics and several biological and pathological parameters.
Animals↗
CA15.3, MCA, CAM26, CAM29 are members of a polymorphic family of mucin-like glycoproteins.
The monoclonal antibodies that define the tumor markers CA15.3, MCA, CAM26 and CAM29 were found to react with coexisting epitopes present on mucin-like glycoproteins. Despite their immunologic relationship, the markers showed distinct concentration levels in various body fluids. Particularly, MCA and CAM26 were high in urine and amniotic fluid. Sera collected from pregnant or lactating women and especially human milk samples contained considerable amounts of CAM29 and MCA, but comparably small quantities of CAM26 and CA15.3. The concentrations of CA15.3, MCA, CAM26 and CAM29 were correlated in serum samples from patients with metastatic breast cancer. The discrepancy between immunologic relationship and dissimilar biologic behavior could be explained by a limited coexistence of epitopes on subsets of heterogeneous polymorphic mucins. All mucin markers which were investigated showed improved sensitivity for metastatic breast cancer compared with the established marker CEA.
Adolescent↗
Value of sonography in monitoring the therapeutic response of mediastinal lymphoma: comparison with chest radiography and CT.
The aim of this retrospective study was to assess the diagnostic value of mediastinal sonography, compared with that of chest radiographs and CT, in the follow-up of patients with mediastinal lymphomas and in the prediction of clinical outcome. The sonograms, chest radiographs, and CT scans of 40 consecutive patients with Hodgkin (n = 29) and non-Hodgkin (n = 11) lymphoma obtained before and after completion of therapy were analyzed blindly and independently by three radiologists and compared with clinical outcome. Nine patients were treated with radiotherapy, 12 with chemotherapy, and 19 with combined therapy. Therapeutic response was assessed from all available clinical and biochemical findings as well as from the combined results of all imaging studies performed on further follow-up. The sonograms showed obvious changes in the size and echogenicity of the mediastinal lymphomas that corresponded closely with the response to therapy. Sonography showed complete regression of the lymphomas in 30 patients who had complete remission. In five patients with incomplete remission, sonographic diagnoses were correct. All lymph nodes, irrespective of size, detected with sonography after a phase of complete remission indicated recurrence (five patients). Sonographic findings corresponded with those of CT in 25 (81%) of 31 cases. Clinical outcome suggested that the sonographic findings were more reliable in the five cases in which CT and sonographic findings conflicted. Chest radiographs were inadequate for monitoring the response of mediastinal lymphomas to therapy; in 17 (43%) of 40 cases, a false impression was obtained of the extent and therapeutic response of mediastinal lymphomas. The results of this study indicate that sonography is clearly superior to chest radiographs and comparable to CT for monitoring patients with mediastinal lymphomas.
Adolescent↗
Membrane transport, sodium balance, and blood pressure regulation.
Essential hypertension is characterized by polygenic inheritance and quantitative and/or qualitative abnormalities of membrane transport systems may function as intermediate phaenotypes. The present review attempts to evaluate the importance of sodium transport systems such as the sodium pump, cotransport and countertransport as aetiological or pathogenetic factors involved in primary hypertension. Furthermore, the relative importance of NaCl balance as an exogenous factor modifying these transport systems is reviewed. Controversial results exist with respect to the activity of the sodium pump and cotransport both as a function of blood pressure and NaCl balance. In contrast, accumulating evidence suggests that the activity of the counter-transport system is increased in essential hypertension and that this may be observed even before the elevation of blood pressure can be documented. In own studies performed in normotensive volunteers on a low (20 mmol/day) and high (320 mmol/day) NaCl intake, lymphocyte antiport activity was significantly higher during chronic NaCl loading. Therefore, alterations of the Na+/H+ antiport system may represent an intermediate phaenotype of gene(s) involved in the genesis of primary hypertension. Preliminary evidence suggests that NaCl balance may be an exogenous modulator of this system.
Animals↗
[Incontinence and toilet training].
Explore the source record for details and available documents.
Aged↗
[Grand mal seizure. Laminar heterotopy of the gray substance].
Explore the source record for details and available documents.
Adult↗