Biomedical subjects

H Osswald

Publications and source records attributed to H Osswald.

At least 73 records · Page 4Linked to original sources

PubMed1994

[Effect of a cisplatin-5-fluorouracil combination chemotherapy on malignant transformation of the epithelium of mouth mucosa].

In a prospective study we examined the effect of preoperative chemotherapy with cisplatinum and 5-fluorouracil (5-FU) in 40 patients with advanced carcinoma of the oral cavity. Histopathologic grading, cell kinetics and immunohistochemical parameters of the mucosa were determined at two different locations. Prior to therapy, histologic dysplasias in the mucosa "close" to the tumor were observed in 75 percent of the patients. Dysplastic changes of the mucosa "far" from tumor were also found in more than one-third of the patients. Our results show that more advanced dysplasias improve only temporarily under the influence of preoperative systemic chemotherapy. Moreover, new dysplasias appearing during chemotherapy and persisting after its termination are probably induced. The results point to a possible carcinogenic potential of the combined chemotherapy schema used.

Antineoplastic Combined Chemotherapy Protocols↗

PubMed1994

Neuromodulatory effects of the renin-angiotensin system on the cat electroretinogram.

PURPOSE: Angiotensin-converting-enzyme (ACE) catalyses the formation of angiotensin II (ANGII), which presumably acts as a central neurotransmitter/modulator. ANGII-related effects have also been observed in the retina. Present in vivo experiments were designed to investigate further ANGII-related effects on retinal neuromodulation. METHODS: In 12 anesthetized cats, electroretinographic measurements were carried out in the dark-adapted state using corneal contact lens electrodes and a Ganzfeld stimulator. Quinapril was used to inhibit ACE. RESULTS: Reducing ANGII-concentration increased sensitivity (0.5 log units) and gain (50%) of the rod b-wave amplitude. The b-wave implicit time was stimulus dependent, shortening at high intensities. The scotopic threshold response and the oscillatory potentials were also influenced by ACE inhibition. However, a-wave and 30 Hz flicker remained unaffected. Effects of Quinapril on ERG-amplitudes were reversed by subsequent ANGII administration, except for the implicit time of the b-wave and scotopic threshold response. CONCLUSIONS: Although these results are accompanied by alterations in systemic blood pressure, several findings support the evidence that the renin-angiotensin system might have a neurophysiologic effect on retinal neurons outside the vascular system. These results are in accordance with immunohistochemical data found by others that point to angiotensinergic cell involvement and thereby further support the concept of angiotensinergic processes in the inner retina from a functional point of view.

Angiotensin II↗

PubMed1993

The NSAID sulindac reverses rectal adenomas in colectomized patients with familial adenomatous polyposis: clinical results of a dose-finding study on rectal sulindac administration.

After colectomy with ileorectal anastomosis (IRA) for treatment of familial adenomatous polyposis (FAP), the rectal mucosa remains, with the risk of malignant change. Locoregional (rectal) sulindac has been applied, with initial higher-dose therapy and subsequent low-dose maintenance therapy to minimise side-effects. The dose-finding study with sulindac suppositories started with a dose of 300 mg sulindac daily per patient over 6 weeks. Depending on proctoscopical evaluation of regression of polyposis, sulindac doses were reduced in predefined steps. Ten of 15 patients developed a complete remission following 42 weeks of treatment, while the rest had partial remission. Responses were recorded 6-24 weeks after beginning sulindac treatment. After 36 weeks, 13/15 patients received 25-50 mg sulindac daily. An increase in the number of partial remissions after 42 weeks of treatment at doses of 100 mg sulindac daily may indicate the first approach to a reduced dose between 100 mg to 25 mg sulindac daily, but may also point to the importance of long-term treatment rather than dose-intense therapy.

Adenomatous Polyposis Coli↗

PubMed1993

Fate of circulating oxalate in rats.

The pharmacokinetics of oxalate were studied in normal and nephrectomized rats with the use of radioisotope-labelled oxalate. The disappearance of [14C]oxalate from the plasma was analyzed with a two-compartment open model. The pharmacokinetic parameters of oxalate were compared with those for inulin. In normal rats, the plasma half-life of the elimination of oxalate was 0.33 +/- 0.06 h and that for inulin was 0.26 +/- 0.05 h (n = 10, mean +/- SD). The volume of distribution for oxalate was 56.7 +/- 6.80 and that for inulin 34.0 +/- 4.79 ml/100 g body weight, indicating that oxalate has access to additional compartments besides the extracellular volume. The total clearance of oxalate was 1.2 times higher than that for inulin. In nephrectomized rats, however, the plasma half-life of the elimination of oxalate was 1.85 +/- 0.34 h (n = 7, mean +/- SD) and that for inulin was 4.26 +/- 0.78 h. The total clearance of oxalate was 177 +/- 29 and that for inulin was 30 +/- 5 microliters/min/100 g body weight. In order to identify the extrarenal elimination route of oxalate, the bile of nephrectomized rats was collected. The hepatic clearance of oxalate was 31.2 +/- 2.7 microliters/min/100 g body weight. The biliary excretion of oxalate accounts for 17.6% of the total clearance in nephrectomized rats. Thus, other elimination processes of oxalate besides renal and hepatic clearance take place.

Animals↗

PubMed1993

[Hypernatremia and kidney function].

Hypernatremia is caused by a water deficit. Cases with hypernatremia and dehydration appear to cluster among children and the elderly with alterations in the level of consciousness thus with no independent access to water. In general, central nervous symptoms prevail. However, thorough examination reveals impaired renal function in many such cases. Animal experiments have shown that rapid increases of the sodium concentration in the renal artery will cause a reduction of renal blood flow (RBF), glomerular filtration rate (GFR) and inhibition of renin secretion, particularly during states of sodium chloride or volume depletion (i.e. with high plasma renin activity). In any other organ hypernatremia leads to vasodilation. The kidney, however, responds with vasoconstriction which can be reversed by the adenosine antagonist theophylline. This finding led to the hypothesis that adenosine mediates the renal response to hypernatremia. Adenosine is generated by the tubules at a higher rate when the kidney is forced to reabsorb large amounts of sodium. In this concept adenosine links metabolic processes of sodium reabsorption with the regulation of organ blood flow causing vasoconstriction via adenosine receptors on the vasa afferentia. This mechanism can explain impaired renal function during acute hypernatremia. It is concluded from experimental evidence that-apart from other therapeutic measures-the recovery of impaired renal function can be improved by administration of the adenosine antagonist theophylline.

Acute Kidney Injury↗

PubMed1993

[Renal effects of adenosine: possible consequences for kidney transplantation].

This review summarizes in the first part the action of adenosine on the kidney. In the second part we discuss the pathophysiological consequences and the possibilities of a pharmacological intervention to improve impaired kidney function. Adenosine causes vasoconstriction in the kidney and reduces glomerular filtration rate (GFR). This action is enhanced in proportion to elevated plasma renin activity. Chronic elevation of ureteral pressure enhances and reduction of renal perfusion pressure attenuates adenosine-induced vasoconstriction. From the kidney-specific relationship between renal blood flow and tubular electrolyte transport the concept is developed which ascribes adenosine a role of a mediator that is essentially contributing to the homeostatic regulation of kidney function. The accumulation of adenosine in the kidney tissue after ischemia or after administration of nephrotoxic substances led to the hypothesis that adenosine is an important intrarenal factor in the pathogenesis of acute renal failure. The possibility to antagonize adenosine actions in the kidney with theophylline was used successfully in a number of experimental studies in acute renal failure and most recently in a study in humans after contrast media administration. Adenosine actions mediated via membrane receptors must be separated from adenosine actions in the cell to increase ATP tissue content. The concept of the "University of Wisconsin" (UW) solution to improve the energy state of the tubular cells appears to be successful, however, we propose that the potential dangerous adenosine actions in the kidney, especially during the reperfusion phase may be antagonized by the administration of theophylline.

Acute Kidney Injury↗

PubMed1992

Feeding but not salt loading is the dominant factor controlling urinary dopamine excretion in conscious rats.

We studied urinary dopamine excretion in three different groups of rats after the following treatment regimens: normal chow and tap water (controls, CON), normal chow and 1% NaCl as drinking water (high salt, HS), and chow with low sodium content plus tap water (low salt, LS). On days 5 and 7 of the respective dietary treatment, rats were placed in metabolic cages. Using a cross over design, chow was given (fed) or withheld (fasted). Urine was collected for 24 h and analyzed for sodium, creatinine, and dopamine. Urinary dopamine excretion did not change in proportion to large differences in sodium excretion in fasted animals. Sodium excretion was enhanced (45%) due to feeding only in the CON group but not in HS and LS rats. However, there was a striking increase in renal dopamine excretion in fed compared to fasted animals, irrespective of their sodium diet: 2.5-fold in CON, 2-fold in HS, and 1.8-fold in LS rats. Urinary creatinine excretion was significantly elevated during the feeding condition compared to fasted animals in all treatment groups. Our results demonstrate that urinary dopamine excretion is dominantly influenced by feeding but not by oral sodium intake in conscious rats. We conclude that 1) the dietary state of the animals should be controlled in experiments on renal dopamine production, 2) renally formed dopamine could be involved in the functional response of the kidney to oral food intake.

Animals↗

PubMed1992

Renal insufficiency induced by parathyroid hormone: influence of the calcium antagonist Gö 6070.

To study the pathogenesis of parathyroid-hormone-induced renal insufficiency and the influence of the new calcium channel antagonist Gö 6070 (Gödecke AG, Berlin, FRG) rats were assigned to three groups (n = 8 each): (1) control, (2) PTH, (3) PTH plus Gö 6070. PTH (30 micrograms/24 h, a nonhypercalcemic dose) was administered i.p. and Gö 6070 (1 mg/kg/24 h) p.o. for 6 days. PTH did not change plasma or urinary calcium and did not induce nephrocalcinosis. The glomerular filtration rate (GFR), however, was decreased (4.9 vs. 10.3 ml/min/kg). Concomitant administration of Gö 6070 attenuated the PTH-induced fall in GFR (6.2 ml/min/kg).

Animals↗

PubMed1991

Adenosine mediates tubuloglomerular feedback response: an element of metabolic control of kidney function.

Numerous studies have shown during the past 10 years that adenosine is present in the normoxic kidney and accumulates when ATP hydrolysis prevails over ATP synthesis. Local generation of adenosine by the macula densa cells and its release into the interstitium of the juxtaglomerular apparatus (JGA) is considered to be the link between the enhanced NaCl concentration in the tubular fluid and the subsequent responses including preglomerular vasoconstriction and reduction of renin release by the juxtaglomerular cells. Micropuncture and microperfusion experiments using specific adenosine agonists and antagonists support the concept that adenosine functions as a mediator in the signal transmission of the JGA.

Adenosine↗

PubMed1990

Activity of various amphiphilic agents in reversing multidrug resistance of L 1210 cells.

Several compounds (bamipine, chlorphenoxamine, estracyt, hycanthone, quinidine, quinine, tamoxifen, trifluoperazine and verapamil) have a common basic structure with the following features: lipophilic aromatic ring system; linked chain hydrophilic N-alkyl group. They are used medically for varying diseases. Their activity in reversing multidrug-resistance (MDR) with other compounds (diethylstilbestrol, beta-estradiol, methylbiguanide, methylpiperazine, testosterone) lacking one of these chemical features is compared. The in vitro test system we used was the nucleoside incorporation assay using parental L 1210 ascites tumor cells and a doxorubicin resistant subline, which expresses the MDR phenotype. The substances lacking one of these features were not effective in reversing the MDR whereas all other tested substances demonstrated modulating potential in the MDR resistant L 1210 cells.

Animals↗

PubMed1990

Aging and endothelin-1 induced vascular contractions.

Contractions produced by endothelin-1 (0.3-30 nM) have been investigated in aorta, renal arteries and mesenteric arteries from 2- and 24-month-old Sprague-Dawley rats. In senescent rats the EC50 values of endothelin-1 for aorta and renal artery were significantly increased (aorta: from 6.2 to 12 nM; renal artery: from 5.2 to 7.8 nM). For mesenteric artery the EC50 value (4.3 nM) was unchanged by aging, whereas the maximal contractile response to endothelin-1 was enhanced (from 8.3 to 11.7 mN). In contrast, there was no significant age-related difference in the maximal endothelin-1 response of aorta and renal artery. The present data demonstrate a reduced sensitivity for aorta and renal artery and an enhanced maximal response to endothelin-1 in the mesenteric artery in senescent rats.

Aging↗

PubMed1990

Differential blockade by nifedipine and omega-conotoxin GVIA of alpha 1- and beta 1-adrenoceptor-controlled calcium channels on motor nerve terminals of the rat.

Electrically evoked release of [3H]acetylcholine ([3H]ACh) from the rat phrenic nerve and its facilitation by stimulation of presynaptic alpha 1- and beta 1-adrenoceptors were investigated in the absence and presence of nifedipine and omega-conotoxin GVIA. Both calcium channel antagonists did not modify electrically evoked [3H]ACh release, but selectively blocked the effect triggered by both facilitatory adrenergic receptors. The increase in [3H]ACh release mediated via beta 1-adrenoceptor activation was abolished by low concentrations (1 nM) of omega-conotoxin GVIA, whereas nifedipine (100 nM) abolished the facilitatory effect mediated via alpha 1-adrenoceptor stimulation. Therefore, the beta 1-adrenoceptor is apparently coupled to a calcium channel that can be regarded as of the N-type, and the alpha 1-adrenoceptor is apparently coupled to a calcium channel that appears as a subtype of the L-type which is not sensitive to omega-conotoxin GVIA.

Acetylcholine↗

PubMed1990

Sacrosine- and prolinedithiocarbamate pretreatment increases the therapeutic efficacy of doxorubicin, methotrexate, teniposide, mitoxantrone or cyclohexylchloroethylnitrosourea in leukemia L1210.

The influence of different doses of the hydrophilic sarcosine- or prolinedithiocarbamate on the chemotherapeutic efficacy of doxorubicin, teniposide, methotrexate, mitoxantrone or cyclohexylchlorethylnitrosourea was evaluated in female B6D2F1 mice bearing leukemia L1210, implanted intraperitoneally. The simultaneous administration of these dithiocarbamates and the drugs used induced no increase of the therapeutic efficacy of the combinations compared to the corresponding dose of the drug and simultaneously applied saline. The results indicate that the subcutaneous pretreatment with sarcosine- or prolinedithiocarbamate increased the therapeutic efficacy of the drugs used compared to the corresponding monotherapy, in which saline was applied in the same interval as the dithiocarbamate and the antineoplastic agents. Sarcosine- or prolinedithiocarbamate applied alone did not influence leukemia L1210. The increase of the efficacy of the drugs used by sequential combination with sarcosine- or prolinedithiocarbamate seems to be influenced predominantly by diminishing the toxicity as well as by modulating the chemotherapeutic action.

Animals↗

PubMed1990

Acute renal failure in man: new aspects concerning pathogenesis. A morphometric study.

The morphometric investigation of the proximal and distal tubules, the cortical interstitium, the intertubular capillaries, the renal corpuscles and the juxtaglomerular apparatuses (JGAs) in 56 cases in the oligoanuric, polyuric, and normuric phases of human acute renal failure (ARF), 6 cases of myeloma kidney with clinically confirmed ARF and 21 control kidneys revealed the following: (1) The main pathological change in human ARF is swelling of the epithelial cells of the proximal and distal tubules. Necrosis of these cells was observed in some cases but usually only as single cell necroses. (2) The interstitium of the cortex and of the outer stripe of the outer medulla is significantly widened in most cases of ARF. (3) In proximal tubules proximal to occluding casts (which were observed only in the plasmacytoma cases), the lumina are not widened but are narrower than normal, and the cross-sectional area of the epithelium is not greater but smaller than normal. (4) The JGAs were significantly larger in kidneys in the oligoanuric phase of ARF (with 1 exception) than in normal kidneys. In the normuric and polyuric phases they were slightly (not significantly) smaller than normal. In myeloma kidneys with occluding casts and/or diffuse interstitial fibrosis, the JGAs were significantly smaller than normal. From these findings it is concluded that: (1) The fall in glomerular filtration rate (GFR) in the postshock phase of ARF is not caused by nonselective back-diffusion of the primary urine through necrotic tubules or by compression of the lumina of the proximal and distal tubules by interstitial edema. A fall in GFR associated with occluding casts in the distal tubules is found only in the myeloma kidney and does not lead to widening of the proximal tubules but to tubular atrophy and narrowing of the lumen. (2) The casts seen in the lumina of the ascending limb of Henle's loop in some cases of ARF, which consist of hemoglobin, Tamm-Horsfall protein or desquamated blebs, do not occlude the lumen, since they are not associated with atrophy or luminal dilatation of the proximal tubules. (3) The JGAs with their secretory product renin-angiotensin II, together with adenosine, which is released in kidneys with ischemic or toxic damage, play a critical role in the pathogenesis of ARF. (4) In myeloma kidneys with ARF, in which the JGAs are markedly atrophic, the potentiated effect of adenosine that has been observed with a chronic absence of urine flow probably leads to a progressive, irreversible drop in GFR associated with tubular atrophy.

ADP-Ribosylation Factor 6↗

PubMed1990

Renal actions of calcium channel antagonists.

The actions of L-channel calcium antagonists on the kidney are the result of direct and indirect effects. The direct effects are characterized by vasodilation, especially when the renal vascular resistance was enhanced beforehand. The increase in glomerular filtration rate is small and transient in most of the clinical trials with chronic administration. An important direct effect of calcium channel antagonists on renal function is the increase of sodium and water excretion by a tubular action that occurs in the absence of hemodynamic changes. The mechanism of the tubular effects of calcium channel antagonists is not understood at present. An indirect effect of calcium channel antagonists on the kidney is the inhibition of the aldosterone secretion by the adrenals. A sodium and water loss due to inhibition of tubular reabsorption leads to an increase in renin activity and aldosterone concentration in the plasma as seen typically with diuretics. The dissociation of renin- and aldosterone increase by calcium channel antagonists is a new finding and contributes favorably to the anti-hypertensive efficacy of calcium channel antagonists. In experimental acute renal failure mainly diltiazem and verapamil improved recovery of kidney function. In kidney transplantation, diltiazem reduced posttransplant acute tubular necrosis and improved primary graft function. It remains to be seen whether other calcium channel antagonists have a similar beneficial therapeutic effect in pathological states of renal function.

Acute Kidney Injury↗

PubMed1989

Generation of nitric oxide by human neutrophils.

Human neutrophils were evaluated for their ability to generate nitric oxide. Neutrophils incubated with superoxide dismutase at 37 degrees C produce nitrite anion at a rate of 1.8 nmols/2 x 10(6) cells/30 min, providing indirect evidence of nitric oxide production. Incubation of the neutrophils with concentrations of serum-opsonized zymosan, N-formyl-methionyl-leucyl-phenylalanine, or phorbol myristate acetate sufficient to stimulate the respiratory burst and lysosomal enzyme release caused no additional nitrite anion production. Glass wool-adherent neutrophils exhibited a similar dissociation of nitrite anion production from the respiratory burst and lysosomal enzyme release. Direct evidence for nitric oxide production was also obtained using nitric oxide-specific chemiluminescence. These results demonstrate that human neutrophils are capable of generating nitric oxide.

Anions↗

PubMed1989

The initiator tRNA acceptance assay as a short-term test for carcinogens. 5. Results with 42 cytostatic drugs.

The activity of 42 cytostatic drugs used for the treatment of human cancer was tested by the initiator tRNA acceptance assay for carcinogens. Of 17 drugs carcinogenic for rodents, 16 (94.1%) gave a positive response in the assay and six (85.7%) out of seven non-carcinogens showed no activity. The predictive value of the test for cytostatics was 91.7%. Treatment of tRNA with several cytostatics resulted in an inhibition of its acceptance for L-methionine. Cyclophosphamide, dibromdulcitol, 5-deoxy-5-fluorouridine and vincristine also inhibited, in addition to this, the charging of unfractionated tRNA from rat liver with L-alanine, L-lysine, L-phenylalanine and L-valine. Some drugs apparently react with the same target nucleoside which is common for all species of tRNA (probably the terminal adenosine residue that is esterified with amino acids). Such compounds do not yield reliable results in the initiator tRNA acceptance assay since this inhibitory effect interferes with the stimulating effect characteristic for carcinogens. However, results of the present study agree well with those obtained earlier with different classes of compounds (N-nitroso compounds, mycotoxins, etc.) and indicate that this newly developed assay may be a useful alternative also for the testing of carcinogenicity of cytostatic drugs.

Amino Acids↗

PubMed1989

Inhibition of noradrenaline release by omega-conotoxin GVIA in the rat tail artery.

1. The perivascular nerves of isolated tail arteries from Wistar rats were stimulated with field pulses (1 Hz, 2 pulses, every 2 min). omega-Conotoxin 10 nmol l-1 depressed neurogenically mediated contractions, but did not influence the contractions to noradrenaline 0.1-0.3 mumol l-1. 2. The inhibitory effect of omega-conotoxin was concentration-dependent (IC50 = 3.8 nmol l-1). It did not reach a steady-state during 30 min incubation and could not be reversed upon subsequent washout for another 60 min. 3. A gradual increase in the Ca2+ concentration of the medium from 1.25 mmol l-1 to 10 mmol l-1 enhanced vasoconstriction and attenuated the action of omega-conotoxin 10 nmol l-1. When a low stimulation intensity (120 mA) was used at high external Ca2+ (10 mmol l-1), similar contractile responses were obtained as under normal conditions (200 mA current, 2.5 mmol l-1 Ca2+). However, the inverse relationship between the effect of the toxin and external Ca2+ remained unchanged. 4. The time-course and degree of the inhibition by omega-conotoxin 3 nmol l-1 was identical in tail arteries of spontaneously hypertensive rats (SHR) and their normotensive controls (WKY). 5. When tail arteries of Wistar rats were preincubated with [3H]-noradrenaline, field stimulation (0.4 Hz, 24 pulses, every 16 min) evoked tritium overflow and vasoconstriction. omega-Conotoxin 30 nmol l-1 inhibited both responses to a similar extent. 6. Our results suggest that omega-conotoxin selectively blocks Ca2+ channels in the terminals of perivascular nerves and thereby reduces the release, but not the contractile effect of the sympathetic transmitter.

Animals↗