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Biomedical subjects

K Sydow

Publications and source records attributed to K Sydow.

At least 19 recordsLinked to original sources
PubMed2006

Tracheal allograft transplantation in rats: the role of different immunosuppressants on preservation of respiratory epithelium.

BACKGROUND: Bronchiolitis obliterans is the most significant complication adversely affecting the survival of lung allograft recipients. Injury and loss of epithelium are associated with obliteration of the airway lumen. The aim of this study was to examine the effects of various immunosuppressants on airway epithelium. METHODS: Tracheae from Brown Norway donors were heterotopically transplanted into the greater omentum of Lewis (allografts) or Brown Norway (isografts) animals. Recipients were treated for 28 days with FK778 (20 mg/kg), tacrolimus (4 mg/kg), or sirolimus (2 mg/kg). Tracheal segments were evaluated for the degree of luminal occlusion as well as the type and percent of luminal epithelial cell coverage. RESULTS: All agents inhibited peritracheal infiltration and luminal obliteration. Tacrolimus- more than sirolimus-treated recipients showed partial preservation of the luminal epithelial coverage, whereas animals that received FK778 showed no respiratory epithelium. The epithelial loss was accompanied by the appearance of fibrous tissue, which replaced the mucosa. CONCLUSIONS: Tacrolimus as well as sirolimus effectively prevented the development of obliterative airway disease whereas tacrolimus and, to a lesser degree, sirolimus preserved epithelial cells as a source of protective cytokines. With FK778 significant airway obliteration was suppressed despite complete epithelial loss. Thus, FK778-treated animals displayed an epithelial-independent inhibitory effect on myofibroblast proliferation.

Animals↗
PubMed2001

[Homocysteine, endothelial dysfunction and cardiovascular risk: pathomechanisms and therapeutic options].

Elevated homocyst(e)ine plasma concentrations are an independent risk factor for cardiovascular disease. Hyperhomocyst(e)inaemia is common in patients with peripheral arterial occlusive disease, coronary heart disease, cerebrovascular disease, carotid artery stenosis and venous thromboembolism. Endothelial dysfunction may be one underlying cause leading to proatherogenic effects associated with hyperhomocyst(e)inaemia. However, the mechanisms which lead to impaired endothelial function in hyperhomocyst(e)inaemia are not fully understood. Recent evidence suggests that homocyst(e)ine may interact with physiological mediators of the endothelial matrix. Oxidative mechanisms and decreased biological activity of endothelium-derived nitric oxide (NO) may also contribute to homocyst(e)ine-associated endothelial dysfunction. B vitamins are essential cofactors in the metabolism of homocyst(e)ine to methionine via the remethylation-pathway (vitamin B12, folic acid) and to cystathionine via the transsulphuration-pathway (vitamin B6). Dietary deficiencies of folic acid, vitamin B12, and vitamin B6 appear to be common among elderly people in the western world and represent one pathogenic factor related to the incidence of hyperhomocyst(e)inaemia. Several studies have demonstrated that dietary supplementation with folic acid and the vitamins B12 and B6 is an efficient means to decrease plasma homocyst(e)ine. No clinical studies are available to date to prove whether reducing homocyst(e)ine levels to the normal range by supplementary B vitamins will also beneficially affect vascular function or cardiovascular risk. Furthermore it is unknown whether moderately elevated homocyst(e)ine concentrations per se may predispose to development of vascular disease, or whether homocyst(e)ine is an indirect marker of cardiovascular disease. Further investigations will be necessary to elucidate the causal relationship between elevated homocyst(e)ine plasma concentrations and the incidence of cardiovascular events, especially since the therapeutic strategies in hyperhomocyst(e)inaemia would differ depending on the underlying pathophysiological mechanisms.

Adult↗
PubMed2000

LDL cholesterol upregulates synthesis of asymmetrical dimethylarginine in human endothelial cells: involvement of S-adenosylmethionine-dependent methyltransferases.

Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. It is formed by protein arginine N-methyltransferases (PRMTs), which utilize S-adenosylmethionine as methyl group donor. ADMA plasma concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and producing proatherogenic changes of endothelial cell function. Four different isoforms of human PRMTs have been identified. Because the release of ADMA from human endothelial cells is increased in the presence of native or oxidized LDL cholesterol, we investigated the potential involvement of PRMT activity and gene expression in this effect. We found that the production of ADMA by human endothelial cells is upregulated in the presence of methionine or homocysteine and inhibited by either of the methyltransferase inhibitors S-adenosylhomocysteine, adenosine dialdehyde, or cycloleucine. This effect is specific for ADMA but not symmetrical dimethylarginine. The upregulation of ADMA release by native and oxidized LDL is abolished by S-adenosylhomocysteine and by the antioxidant pyrrollidine dithiocarbamate. Furthermore, a methyl-(14)C label is transferred from S-adenosylmethionine to ADMA but not symmetrical dimethylarginine, in human endothelial cells. The expression of PRMTs is upregulated in the presence of native or oxidized LDL. Our data suggest that the production of ADMA by human endothelial cells is regulated by S-adenosylmethionine-dependent methyltransferases. This activity is upregulated by LDL cholesterol, which may be due in part to the enhanced gene expression of PRMTs. In concentrations reached by stimulation of methyltransferases (5 to 50 micromol/L), ADMA significantly inhibited the formation of (15)N-nitrite from L-[guanidino-(15)N(2)]arginine. These findings suggest a novel mechanism by which ADMA concentration is elevated in hypercholesterolemia, leading to endothelial dysfunction and atherosclerosis.

Arginine↗
PubMed2000

Plasma concentration of asymmetric dimethylarginine, an endogenous inhibitor of nitric oxide synthase, is elevated in monkeys with hyperhomocyst(e)inemia or hypercholesterolemia.

Hyperhomocyst(e)inemia is associated with endothelial dysfunction. Mechanisms responsible for endothelial dysfunction in hyperhomocyst(e)inemia may involve impaired bioavailability of endothelium-dependent nitric oxide. We tested the hypothesis that hyperhomocyst(e)inemia is associated with an elevated plasma concentration of asymmetric dimethylarginine (ADMA), an endogenous inhibitor of nitric oxide synthase. One group of adult cynomolgus monkeys was fed either a control or hyperhomocyst(e)inemic diet for 4 weeks in a randomized crossover design. The second group was fed an atherogenic diet that produces both hyperhomocyst(e)inemia and hypercholesterolemia for 17 months, followed by an atherogenic diet supplemented with B vitamins for 6 months to decrease plasma homocyst(e)ine concentration. Human endothelial cells were used to study the effects of methionine and homocysteine in the presence or absence of B vitamins or the methylation inhibitor S-adenosylhomocysteine on the formation of ADMA and its inactive stereoisomer, symmetric dimethylarginine. The hyperhomocyst(e)inemic diet produced 2- to 3-fold increases in plasma levels of homocyst(e)ine and ADMA (both P<0.05). The atherogenic diet also produced elevated plasma levels of homocyst(e)ine and ADMA (both P<0. 05). Supplementation of the atherogenic diet with B vitamins decreased the plasma levels of homocyst(e)ine but did not affect the plasma levels of ADMA or endothelial function. There was a strong correlation between plasma ADMA and homocyst(e)ine and a strong inverse correlation between ADMA and carotid artery relaxation to acetylcholine. ADMA release by cultured endothelial cells was significantly increased in the presence of methionine or homocysteine. This effect was blocked by S-adenosylhomocysteine but not by B vitamins. We conclude that plasma levels of ADMA are elevated in hyperhomocyst(e)inemia. Because ADMA acts as a competitive inhibitor of endothelial nitric oxide synthase, these findings suggest a novel mechanism for impaired endothelial function in hyperhomocyst(e)inemia.

Animals↗
PubMed1996

Quantification of the negative feedback mechanism between pituitary and thyroid in subjects with normal thyroid function.

Using sufficiently sensitive and precise assays, we systematically investigated the correlation between thyrotropin, thyroglobulin, index of free thyroxine and index of free triiodothyronine after different doses of thyroxine (25, 50, 100, 150 micrograms), which were administered daily for 10 days to individuals with normal thyroid function and in a control group. Analysis of the data using relative median values expressing changes to basal values before administration of thyroxine yielded the following results: (i) thyrotropin and thyroglobulin decreased monoexponentially, depending on the doses of thyroxine administered; (ii) the extent of their decrease showed a linear correlation with the dose of thyroxine administered and was greater for thyrotropin than for thyroglobulin; (iii) the relative velocity of their decrease increased monoexponentially with the dose of thyroxine and did not differ between thyrotropin and thyroglobulin. These results provide strong evidence for a clear quantitative reaction of the feedback mechanism and confirm that the secretion of thyroglobulin is a physiological process dependent on thyrotropin. The high intra-individual variations obtained for thyrotropin were probably due to its pulsatile secretion.

Adolescent↗
PubMed1996

[Mucociliary clearance of radically operated maxillary sinuses and effect of endoscopic ethmoid bone revision on the mucociliary system].

Twenty-six maxillary sinuses (of 20 patients) were studied following Caldwell-Luc procedures. Surgery had been performed between 1 to 27 years previously. Follow-up studies included nasal endoscopy, coronal computed tomography and camera-sequence scintigraphy. Findings demonstrated that normalization of disturbed mucosal function was possible after surgery. Indications for revision endoscopic sinus surgery are discussed, as are the limitations of surgery.

Ciliary Motility Disorders↗
PubMed1995

[Effect of the phytogenic secretolytic drug Gelomyrtol forte on mucociliary clearance of the maxillary sinus].

BACKGROUND: To date, there has not been sufficient experimental evidence to demonstrate the pharmacological effect of secretolytic and mucolytic drugs. METHODS: Scintigraphic studies to detect the mucociliary clearance in the maxillary sinus before and after application of the secretolytic drug Gelomyrtol forte were performed on four healthy persons and one patient after sinus surgery. The most important parameter was the mucociliary transport velocity of the "region of interest-maxillary sinus" and the increase of radioactivity accumulated in a tampon placed in the middle meatus of the nose. Measurements were done with a gamma-camera, 99 m Technetium-sulphurcolloid was used as the radiopharmacentical. A dose of 1 MBq in 0.2 ml NaCl-solution was injected into the maxillary sinus. RESULTS: The results show a clear increase of mucociliary transport velocity in the maxillary sinus after intake of secretolytics in connection with an increase of radioactivity in the tampon. DISCUSSION: The results can be explained by the secretolytic and secretomotoric effects of the investigated drug. CONCLUSION: The study reveals that ethereal oils have secretolytic effects and also have a pharmacological effect on the mucociliary apparatus.

Adult↗
PubMed1992

Practical approach for determining glomerular filtration rate by single-injection inulin clearance.

We compared the glomerular filtration rate as measured by a single-injection inulin clearance with that measured by a standard isotope method with 99mTc-labeled diethylenetriaminopentaacetic acid in 21 subjects with glomerular filtration rates greater than 35 mL/min. After a bolus injection of 5 g of inulin, blood samples were taken 20, 45, 90, 120, 145, 180, and 240 min afterwards. Inulin was measured by optimized chemical or enzymatic methods of high analytical sensitivity to determine inulin at low concentrations. We used the one-compartment model and inulin concentrations measured at two sampling times to calculate the glomerular filtration rate from the data of the disappearance curve of inulin. Inulin concentrations at 20 and 240 min after injection of the inulin bolus were suited to estimate glomerular filtration rate by this procedure, resulting in values (y) comparable with those obtained by isotope technique (x). The relationship to the isotope technique was characterized by the equation y = +4.80 mL/min + 0.92x (r = 0.97). The single-injection inulin clearance determination can detect a decrease of glomerular filtration rate at the beginning of kidney damage, given that our study included subjects with glomerular filtration rates greater than 35 mL/min. We conclude that the glomerular filtration rate can be determined by analyzing only two blood samples after a bolus injection of inulin.

Adult↗
PubMed1991

[Experimental studies of the physiology of the paranasal sinuses].

The mucociliary clearance of the maxillary sinus mucosa was studied by 99mTc-SC in 38 healthy subjects. The mucociliary transport rate was relatively constant under physiological conditions so that it was possible to describe a normal range with a narrow variation. This range can be used to estimate the physiological responses of the mucociliary apparatus, and to define pathological disorders. In 3 cases we saw a slow clearance which has never been described before in the sinuses. In our experimental study we showed that the mucociliary activity of the sinuses is not only a mechanism to clean the mucosa, but is moreover a controlled system which can be activated by a physiological stimulus. After the stimulation the production of mucus and its outflow to the nose increased. Physiological and phylogenetic aspects of the existence of the sinuses in vertebrates and man are discussed.

Adult↗
PubMed1991

[Nuclear medicine studies of the regenerative behavior of paranasal sinus mucosa after functional endoscopic ethmoid bone surgery].

The mucociliary clearance of the maxillary sinus mucosa was studied before and 6-18 months after functional sinus surgery using 99mTc-SC in 34 sinuses of 22 patients with chronic inflammation of the ethmoid and maxillary sinus. Before operation the mucociliary transport was very slow and sometimes absent. In the postoperative interval between 6 and 18 months we saw a significant return of the mucosal function. In 56% of the sinuses investigated the postoperative clearance rate was within the normal range. We also recorded a similar trend in allergic patients, although there was not such a clear return to normal of the mucociliary clearance, and the rates were not within the normal range. We found no recovery of the mucociliary function in 11 sinuses of 7 patients with impaired healing. Decisions on subsequent treatment were based on postoperative nasal endoscopy and functional mucosal repair.

Chronic Disease↗
PubMed1989

[The use of imaging procedures following kidney transplantation--diagnostic strategy].

Despite the continuously increasing number of successfully transplanted kidneys, graft and patient are still "threatened" by several postoperative complications as acute and chronic rejection, acute tubular necrosis, urologic and vascular complications and disorders caused by immunosuppressive medication. An early and safe detection of these conditions is of high clinical importance and a challenge to diagnostic imaging. All radiologic methods and nuclear medicine have their value for transplantation diagnostics, but in recent years a trend to noninvasive methods with no contrast media and little discomfort to the patient is clearly visible (sonography, magnetic resonance). Rational diagnostic strategies for various conditions after renal transplantation are described.

Diagnostic Imaging↗
PubMed1988

[The low molecular weight proteins ribonuclease, beta 2 microglobulin and lysozyme in the serum and urine of patients with chronic kidney diseases].

The diagnostical relevance of the low-molecular proteins ribonuclease, beta 2-microglobulin and lysozyme in serum and urine to detect a reduced glomerular filtration rate was examined in 52 patients with chronic renal diseases. The radioisotope clearance using 99mTc-DTPA was the base reference; the reference values of the low-molecular proteins were estimated in a control group. Ribonuclease was increased above the upper borderline value, if the glomerular filtration rate was lower than 1.24 ml s-1. Creatinine, beta 2-microglobulin and lysozyme remain yet in part in the normal range. The estimation of the ribonuclease in serum is suitable to detect an impaired glomerular filtration rate if the creatinine value is still not increased. Thereby, the diagnostics in renal diseases may be improved in the creatinine-blind area.

Adult↗
PubMed1988

[Percutaneous removal of kidney calculi and extracorporeal shockwave lithotripsy in patients with hemorrhagic diatheses].

Hemorrhage is the main complication of percutaneous kidney stone removal. Shock-wave lithotripsy also may causes bleeding complications. It seems that both procedures are contraindicated on patients with coagulation disorders. On the base of two cases the specification of treatment by patients with hemorrhagic diatheses is demonstrated. Modern treatment modalities of urinary stone disease are also applicable to those patients, when attention is paid to some conditions and attentive measures are taken.

Adult↗
PubMed1988

[Standardization of methods and assessment of conventional and radionuclide clearance investigations: recommendations of the Renal Diagnostics Study Group of the Society of Nephrology, GDR].

Recommendations of the Study Group "Renal Function Diagnostics" of the Society of Nephrology to the performance of the steady state clearance using inulin or PAH and the slope clearance with radionuclides for estimation of effective renal plasma flow are presented. These investigations are indicated in the early recognition and follow-up of latent or residual disturbance of the renal function in the creatinine-blind area. Recommendations have been done on selection and dosage of test substances, timing of examination and evaluation of results.

Blood Pressure↗
PubMed1987

Diagnostic significance of different urinary enzymes in patients suffering from chronic renal diseases.

The urinary enzymes alanine aminopeptidase (EC 3.4.11.2), alkaline phosphatase (EC 3.1.3.1), gamma-glutamyltransferase (EC 2.3.2.2), N-acetyl-beta-D-glucosaminidase (EC 3.2.1.30), and ribonuclease (EC 3.1.4.22) were measured in 66 healthy persons and 52 patients suffering from chronic renal diseases (pyelonephritis, glomerulonephritis). The residual renal function of patients characterized by 99mTc-diethylenetriaminopentaacetate isotope clearance was only moderately reduced. Except for gamma-glutamyltransferase, patients generally showed increased urinary enzyme excretions. N-Acetyl-beta-D-glucosaminidase was more sensitive to detect renal dysfunction than the other enzymes and the conventional parameters serum creatinine, total protein excretion, and the measurement of glomerular filtration rate. The determination of this enzyme can be recommended as a suitable diagnostic parameter in nephrology.

Acetylglucosaminidase↗