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Biomedical subjects

J Sadowski

Publications and source records attributed to J Sadowski.

At least 37 records · Page 2Linked to original sources
PubMed2000

Differential effect of frusemide on renal medullary and cortical blood flow in the anaesthetised rat.

In addition to its known effect on renal tubular transport, frusemide (furosemide) has been shown to affect renal circulation. This study in the anaesthetised rat examined the influence of frusemide (bolus 0.25 or 0.5 mg kg(-1) I.V., then infusion delivering the same dose over 1 h) on renal cortical and medullary circulation measured as laser-Doppler blood (cell) flux. The responses were compared with simultaneously measured changes in renal excretion and in the tissue admittance, an index of medullary ionic hypertonicity of the interstitium. Renal vascular responses to frusemide were significant but not dose dependent. During low-dose frusemide infusion cortical flux decreased 11.5 +/- 0.9% and medullary flux decreased 32.3 +/- 3.5% (difference significant at P < 0.001). During high-dose infusion the decreases were by 13.5 +/- 1.4 and 29.3 +/- 3.8%, respectively (difference significant at P < 0.001). Sodium excretion increased 15-fold (by 3.7 +/- 0.4 micromol x min(-1)) and 30-fold (by 5.9 +/- 1.1 micromol x min(-1)) during low- and high-rate infusion of frusemide, respectively. By contrast, medullary tissue admittance decreased similarly with the two doses: maximally by 13.4 +/- 1.4 and 10.9 +/- 0.9%, respectively. The observations that an exaggerated post-frusemide decrease in blood flow within the medulla coincided with decreasing tissue admittance in this zone and that neither medullary blood flow nor admittance changes were related to the dose suggest a causal relationship between interstitial ionic hypertonicity and vascular resistance. We propose that the post-frusemide decrease in medullary tissue NaCl depressed medullary circulation by inhibiting local generation of vasodilator prostaglandins.

Animals↗
PubMed1999

Exaggerated volume expansion natriuresis in rats preloaded with hypertonic saline: a paradoxical enhancement by inhibition of prostaglandin synthesis.

In preliminary experiments rats preinfused with hypertonic saline showed exaggerated natriuresis after an additional small volume expansion (SVE). This was systematically studied in anaesthetized Wistar rats prepared for clearance studies of the left kidney and measurements of medullary blood flow (MBF, laser-Doppler technique) and tissue electrical admittance (Y ), an index of interstitial ion concentration. The rats were preinfused i.v. with 3 mL of 5% NaCl during 90 min. A subsequent injection of isotonic saline, 0.5% of body weight, increased sodium excretion (UNaV ) from 2.1 +/- 0.5 to 4.5 +/- 1.1 micromol min-1 and urine flow (V ) from 12.0 +/- 2.3 to 24.3 +/- 5.6 microL min-1 (P < 0.02). The same volume of whole blood increased UNaV from 5.0 +/- 1.4 to 8.7 +/- 1.7 micromol min-1 and V from 22.3 +/- 5.1 to 37.4 +/- 5.9 microL min-1 (P < 0.01). The glomerular filtration rate, MBF and Y did not change. In rats preinfused with 0.9% saline no natriuresis was observed after SVE. To examine if prostaglandins (PG) were involved in SVE natriuresis, indomethacin (Indo), 5 mg kg-1 or sodium meclophenamate (Meclo), 7.5 mg kg-1, were added to the injected 0.9% saline. Paradoxically, both PG synthesis inhibitors enhanced natriuresis to SVE. After Indo UNaV increased from 2.0 +/- 0.6 to 7.6 +/- 1.3 micromol min-1, significantly more than after SVE alone (P < 0.001). At higher baseline UNaV, the increase with Meclo from 4.5 +/- 1.2 to 13.5 +/- 1.8 micromol min-1 was significantly higher than after whole blood infusion (P < 0.001). MBF decreased and Y increased after both inhibitors. Further studies are required to explain the enhancement of natriuresis after blockade of PG synthesis.

Animals↗
PubMed1998

A scoring scheme for discriminating between drugs and nondrugs.

A scoring scheme for the rapid and automatic classification of molecules into drugs and nondrugs was developed. The method is a valuable new tool that can aid in the selection and prioritization of compounds from large compound collections for purchase or biological testing and that can replace a considerable amount of laborious manual work by a more unbiased approach. It is based on the extraction of knowledge from large databases of drugs and nondrugs. The method was set up by using atom type descriptors for encoding the molecular structures and by training a feedforward neural network for classifying the molecules. It was parametrized and validated by using large databases of drugs and nondrugs (169 331 molecules from the Available Chemicals Directory, ACD, and 38 416 molecules from the World Drug Index, WDI). The method revealed features in the molecular descriptors that either qualify or disqualify a molecule for being a drug and classified 83% of the ACD and 77% of the WDI adequately.

Databases, Factual↗
PubMed1998

Osmotic hypertonicity of the renal medulla during changes in renal perfusion pressure in the rat.

1. The relationship between renal perfusion pressure (RPP) and ion concentration in renal medulla was studied in anaesthetized rats. RPP was changed in steps within the pressure range 130-80 mmHg, while tissue electrical admittance (Y, index of interstitial ion concentration) and medullary and cortical blood flow (MBF and CBF; laser Doppler flowmetry) were measured, along with glomerular filtration rate (C in) and renal excretion. 2. With a RPP reduction from 130 to 120 mmHg, tissue Y remained stable; at 100 and 80 mmHg, Y was 5 and 17 % lower, respectively, than at 120 mmHg. 3. CBF fell less than RPP (partial autoregulation) in the range 130-100 mmHg only. MBF was autoregulated within 120-100 mmHg, but not above or below this range. 4. Each step of RPP reduction was followed by a decrease in sodium and water excretion (UNaV and V). The osmolality of excised inner medulla fragments was similar at 120 and 105 mmHg (586 +/- 45 and 618 +/- 35 mosmol (kg H2O)-1, respectively) but lower at 80 mmHg (434 +/- 31 mosmol (kg H2O)-1, P < 0.01); the ion concentration changed in parallel. 5. The data show that medullary hypertonicity was well preserved during RPP fluctuations within 130-100 mmHg, but not below this range. RPP-dependent changes of UNaV and V were not clearly associated with changes in solute concentration in medullary tissue.

Animals↗
PubMed1998

Protein-calorie malnutrition does not predict subtle vitamin K depletion in hospitalized patients.

OBJECTIVE: Recent studies suggest that subtle vitamin K depletion has far-reaching consequences. As this entity is not associated with prothrombin time elevation, it is important to determine whether alternate methods can help identify it. We investigated subtle vitamin K depletion in a hospital setting and determined whether protein calorie malnutrition predicts its presence. DESIGN, SETTING, SUBJECTS: Using a high-pressure liquid chromatography (HPLC) assay of plasma phylloquinone and a food frequency questionnaire for phylloquinone intake, we examined the phylloquinone status of 27 hospitalized patients with normal coagulation parameters, no liver disease, and no recent warfarin use. We assessed protein-calorie nutritional status with Reilly's criteria and anthropometrics. RESULTS: 51% of patients (95% CI = 31% to 70%) had evidence of subtle vitamin K depletion as defined by a subnormal plasma phylloquinone concentration. Patients whose phylloquinone intake was less than the Recommended Daily Allowance (RDA) over the preceding year had lower plasma phylloquinone concentrations when compared to other patients: median (range) 0.106 nmol/l (0.022-0.461) versus 0.301 nmol/l (0.067-3.928), respectively (P = 0.023). Plasma phylloquinone concentrations were no different, however, between well-nourished and malnourished patients: median (range) 0.245 nmol/l (0.022-0.522) versus 0.188 nmol/l (0.067-3.928), respectively (P=0.782). CONCLUSIONS: Subtle vitamin K depletion is common among hospitalized patients and protein-calorie malnutrition does not predict its presence.

Adult↗
PubMed1998

Mechanism of vasopressin natriuresis in the dog: role of vasopressin receptors and prostaglandins.

Renal effects of physiological amounts of vasopressin were studied in conscious dogs during servocontrolled overhydration (2% body wt). During infusion of vasopressin (50 pg . min-1 . kg body wt-1), plasma vasopressin concentration increased to 2.30 +/- 0.20 pg/ml compared with 0.12 +/- 0.03 pg/ml during control (water diuresis). With vasopressin infusion, urine flow was significantly lower (0.30 +/- 0.10 ml/min) and sodium excretion (UNaV) was significantly higher (58.0 +/- 15.8 micromol/min) than without vasopressin (4.6 +/- 0.4 ml/min and 14.4 +/- 4.1 micromol/min, respectively). Deamino-[Cys1,D-Arg8]vasopressin, a V2 receptor agonist (4 pg . min-1 . kg-1), mimicked the antidiuretic response (0.20 +/- 0.03 ml/min) without changing UNaV (9.7 +/- 4.4 micromol/min). Indomethacin given during arginine vasopressin (AVP) infusion suppressed prostaglandin E2 excretion, intensified the antidiuresis (0.10 +/- 0.02 ml/min), and abolished the natriuresis (13.4 +/- 3.7 micromol/min). During AVP infusion, UNaV was highly correlated (r = 0.85) with prostaglandin E2 excretion. Blood pressure, glomerular filtration rate, plasma atrial natriuretic peptide concentration, and the rate of proximal tubule reabsorption (derived from lithium clearance) were similar in all series. The data indicate that, in the dog, physiological amounts of vasopressin can induce natriuresis, probably through activation of non-V2 receptors and the intrarenal synthesis of prostaglandins.

Animals↗
PubMed1998

[Stents for treatment of transluminal percutaneous coronary angioplasty (PTCA) complications].

UNLABELLED: This study describes initial results of stent implantation in bailout situations in 38 patients with obstructive dissection after percutaneous transluminal coronary angioplasty (PTCA). Before stent introduction 1.8% of all patients after PTCA required emergency bypass grafting (CABG) because of postprocedural complications. In 1997 the rate of such emergency operations decreased to only 0.5% (p < 0.05). The success rate of stent deployment in patients included in the study was 95%. Mean final inflation pressure used for stent deployment was 12.0 +/- 2.3 atm. After stent implantation average residual stenosis was -0.81 +/- 5.75%. Of the 38 patients, 15 (40%) were treated before stent implantation with prolonged inflations with perfusion catheter. Bailout stenting was performed in 10 (25%) patients undergoing PTCA for restenotic lesions. The stents were placed in the left anterior descending coronary artery in 26 patients (69%), left circumflex coronary artery in 3 patients (8%), and in the right coronary artery in 9 patients (23%). Before bailout stenting 28 patients (75%) presented with type C and D dissection. One patient (2.5%) developed acute stent thrombosis. No episodes of subacute stent thrombosis were noted. During six-months clinical follow up no death and no Q-MI were observed. Angiographic follow up restenosis rate was 13/30 (43%), predominantly in patients treated with prolonged perfusion balloon inflations before stent implantation. The incidence of repeated PTCA and elective CABG due to restenosis was 12/30 (40%) and 1/30 (3%), respectively. There were no vascular complication at the puncture site. IN CONCLUSION: the introduction of coronary stenting has provided an excellent non-surgical modality for treatment of imminent or acute vascular closure complicating coronary angioplasty.

Adult↗
PubMed1998

[Calcification of allogenic aortic heart valves].

The material used for the studies consisted of allogenic aortic valves (AAV) collected from 14 individuals. The necessity of AAV replacement arose from growing circulation insufficiency and AAV dysfunction. The aim the study was the determination of the elemental composition and crystallographic structure of the inorganic deposits in AAV. Moreover, the results of the physicochemical investigations were correlated with clinical data (age of the patient, time between valve replacement surgeries, endomyocarditis, number of infections during last 12 months, arterial hypertension and disturbance of the lipid balance) and with echocardiographic examinations (cusp mineralization and perforation, vegetation, systolic and diastolic dimensions of the left ventricle, maximal and average gradient through allograft valve as well as range of the recoil wave to left ventricle). It was found that mineralization of the AAV cusps was a time-dependent process and took place predominantly at the surface of the cusp. The elemental composition and crystallographic data revealed that the inorganic deposits in AAV were composed of hydroxyapatite crystals. However, the presence of other calcium salts was also found. The development of the mineralization process in AAV does not correlate with endomyocarditis, arterial hypertension and the disturbance of the lipid balance. Probably, endomyocarditis and arterial hypertension induce the pathologic alternations of AAV independently from the mineralization process. The echocardiographic estimations of the pathomorphologic changes of the aortic valve cups are not always consistent with the results of the physicochemical studies.

Adult↗
PubMed1998

[Coronary bypass grafting after failed percutaneous angioplasty (PTCA)].

Between January 1991 and September 1997, in the Cardiovascular Surgery Department of the Institute of Cardiology of Jagiellonian University Medical School, 23 patients underwent emergency CABG due to acute myocardial ischaemia in result of failed PTCA. Over the same period of time invasive cardiologists performed 1883 PTCAs out of which 23 (1.2%) were emergency cardiosurgical procedures, and in 38 patients, stents were implanted in the damaged coronary arteries. The patients' age ranged from 37 to 67 years (median 52.2). In all patients good left ventricular function was preserved, median ejection fraction being 64%. Two patients required IABP to support left ventricular function. 1-4 bypass grafts were implanted (median 1.9 per patient). In one patient, internal mammary artery was collected and then implanted into anterior interventricular branch. The most common complication was myocardial infarction which occurred in 12 patients (52%). In ten patients low output was observed postoperatively. One operated patient (a female died (4.3%). The mean time of hospitalization was 11 days. Emergency myocardial revascularisation procedures performed after failed PTCA, bring higher risk of mortality and dangerous postoperative complications.

Adult↗
PubMed1998

[Aortic dissecting aneurysm in a patient with Marfan syndrome and an artificial aortic valve].

We present patient with the Marfan syndrome in whom the dissecting abdominal aortic aneurysm comprising the left iliac and femoral artery was diagnosed two years after the implantation of an artificial aortic valve. The chest CT showed the extention of the ascending aorta without the aortic dissection features. The patient was taken into the clinic in a very bad general condition with sinus tachycardia, the left ventricular failure together with pulse absence in all standard places of pulse measurement in the left lower limb. During the TEE examination the dissecting aneurysm of type I according to De Bakey's classification and the normal function of the artificial aortic valve were recognized. Colour Doppler revealed the primary entry site above the sinus of Valsalva. The patient was qualified for an urgent surgical intervention. The diagnosis was confirmed during the operation. The patient had resection of aneurysm with Dacron tube replacement. After the cardiosurgical intervention the ischaemic symptoms of the left lower limb retreated, the size of the heart diminished in the chest X-ray and TTE examination. The left ventricular ejection fraction increased from 45% to 62%. The TEE of the patient proved the most accurate and precise method of the diagnosis of the aortic dissection. The obtained information was sufficient to decide on the surgical intervention.

Aortic Dissection↗
PubMed1997

Clinical and echocardiographical study of the aortic homograft implantations in patients with Marfan syndrome.

The aim of the study was to assess the long-term results of surgical treatment with homogenic aortic grafts (HAGs) implantation in patients with Marfan syndrome. There were 31 patients with Marfan syndrome and aortic aneurysm who were operated on between 1980 and 1996. Aortic dissection was diagnosed in 14 patients, DeBakey Type I in six patients and Type II in eight patients. Four patients had to be operated urgently in cardiogenic shock with cardiac tamponade. Sealing up and reinforcement with strip of felt or Gore-Tex has been applied in 22 patients. The surgical modifications mentioned above have been applied since 1987 in all patients with the diameter of the aortic ring exceeding 30 mm or with active infective endocarditis or during reoperation. In 16 patients the space between the aortic homograft and patients own aortic wall was joined to the right atrial auricle. Patients were followed up for 12-179 months (average: 94.6 +/- 499). Three patients died in the early postoperative period and four patients died in the late postoperative period. Rethoracotomy because of bleeding complications was necessary in five patients. HAG damage was responsible for six other reoperations-new HAGs have been implanted in three patients and artificial prostheses were implanted in the other three patients. In the late follow-up period significant improvement in cardiac performance was observed in 24 patients (NYHA I or II). Survival probability of 15 years for the whole group was 80%. The lowest survival probability has been shown in the group of patients with DeBakey Type I aortic dissection (35% survived 15 years after operation). Echocardiographic follow-up has shown that the pressure gradient in HAG was low (7.4 +/- 6.2 mmHg). Only in two patients did the HAG gradient exceeded 20 mmHg. There were no significant differences concerning aortic ring diameters, dimensions of HAG and echocardiographic parameters between the group with surgical modifications, i.e. sealing up and reinforcement with strip of felt or Gore-Tex applied and the group in which these modifications were not applied. Homogenic aortic graft implantation as a method of surgical treatment of aortic aneurysm in patients with Marfan syndrome avoids postoperative anticoagulation, results in substantial improvement of cardiac performance and prolongs life. Surgical treatment should be considered in asymptomatic patients with large aneurysms (exceeding 55-65 mm) in patients with Marfan syndrome because there is a high risk of death in this group of patients in the case of dissection.

Adolescent↗
PubMed1997

A hybrid approach for addressing ring flexibility in 3D database searching.

A hybrid approach for flexible 3D database searching is presented that addresses the problem of ring flexibility. It combines the explicit storage of up to 25 multiple conformations of rings, with up to eight atoms, generated by the 3D structure generator CORINA with the power of a torsional fitting technique implemented in the 3D database system UNITY. A comparison with the original UNITY approach, using a database with about 130,000 entries and five different pharmacophore queries, was performed. The hybrid approach scored, on an average, 10-20% more hits than the reference run. Moreover, specific problems with unrealistic hit geometries produced by the original approach can be excluded. In addition, the influence of the maximum number of ring conformations per molecule was investigated. An optimal number of 10 conformations per molecule is recommended.

Anti-Arrhythmia Agents↗
PubMed1997

Cardiovascular and renal effects of endothelin receptor blockade with PD 145065 and interaction with urodilatin.

Role of endogenous endothelins (ET) in the control of cardiovascular system and renal function, and ET interaction with urodilatin (URO) were studied in anaesthetized rats. Activity of ET was blocked using PD 145065 (5 mg kg-1 body wt i.v.) a non-selective antagonist of ETA and ETB receptors. PD 145065 decreased mean arterial blood pressure (MBP) from 114 +/- 4 to 109 +/- 4 mmHg and the renal blood flow (RBF) from 6.6 +/- 0.3 to 5.8 +/- 0.4 mL min-1 (P < 0.02) and increased renal vascular resistance (RVR) from 17.7 +/- 1.2 to 20.1 +/- 2.1 mmHg min mL-1. Heart rate (HR) and renal function were not affected. URO was infused i.v. at 0.1 nmol min-1 kg-1 body wt without or with previous ET receptor blockade. After pre-treatment with PD 145065, infusion of URO decreased MBP more than did URO alone: 15 +/- 3% vs. 7 +/- 2% (P < 0.05). RVR and HR did not change after URO alone but decreased with URO given to PD 145065 treated rats (19 +/- 5% and 14 +/- 3%, respectively, P < 0.01). It is concluded that in anaesthetized surgically prepared rats endogenous ET can cause renal vasodilation, in contrast to constriction of systemic vasculature. Enhancement by ET blockade of vascular systemic and renal effects of URO supports ET interaction with natriuretic peptides in the control of cardiovascular and renal function.

Animals↗
PubMed1997

Reinvestigation of water diuresis in the rat: role of anesthesia and acute surgery.

Renal effects of water loading on urine flow rate (V) and concentration (Uosm) were studied in Wistar rats subjected to minor or extensive surgery, under different kinds and level of anesthesia. In the explanted kidney of chronically prepared rats, under light chloralose anesthesia, 1 h.i.v. hypotonic fluid load increased V of the experimental (left) kidney 11 fold while Uosm decreased from 1181 +/- 142 to 210 +/- 80 mosm kg/H2O. In the acutely exposed kidney, under Inactin anesthesia, V increased 5 fold and Uosm decreased from 785 +/- 170 to 204 +/- 57 mosm/kg H2O. In similar experiments under Nembutal anesthesia V increased 4 fold but the urine did not become hypotonic. After acute surgery under Inactin anesthesia water diuresis can be induced but urine concentration before water loading is impaired. Urine hypotonicity after water loading is not achieved in acute experiments under Nembutal--an unsuitable approach to studies of water diuresis. Thus, a transition from antidiuresis to urine dilution can best be accomplished in the chronic explanted kidney model under light anesthesia and without invasive surgery.

Anesthesia↗
PubMed1997

Simultaneous recording of tissue ion content and blood flow in rat renal medulla: evidence on interdependence.

The relationship of renal medullary tissue ion concentration and medullary blood flow (MBF) has never been closely evaluated because of limitations of available measuring methods. In an attempt to overcome this difficulty, an integrated probe was developed for simultaneous recording in rat renal medulla of tissue electrical admittance (Y), an index of interstitial ion concentration, and tissue perfusion with blood (laser-Doppler method). During spontaneous-selective MBF variations tissue Y showed inverse changes (r = -0.77, P < 0.001). The inverse correlation of the two variables was also seen after MBF has been reduced (-43%) by indomethacin, 5 mg/kg body wt iv (r = -0.77, P < 0.01). A modest selective MBF reduction (15%) induced by glibenclamide, an inhibitor of ATP-dependent K channels, did not alter medullary tissue admittance. The data support experimentally the concept that the rate of medullary tissue perfusion with blood is one determinant of interstitial solute concentration; however, changes in the latter were demonstrable only with major alterations of the MBF.

Animals↗
PubMed1996

Genetic and physical mapping in Brassica diploid species of a gene cluster defined in Arabidopsis thaliana.

We report the genetic and physical analysis by pulse field gel electrophoresis (PFGE) in three Brassica diploid genomes for a cluster of five genes characterized in a selected segment of 15 kb on chromosome 3 of Arabidopsis thaliana, encoding a Bradyrhizobium CycJ homologue (At1), a rat p67 translation factor homologue (At2), an Em-like (early methionine) protein (At3), chlorophyll synthase (At4) and a yeast Sac1 homologue (A5). The Arabidopsis gene array was found to be conserved on a single linkage group in each of the Brassica genomes. However, partial complexes were found to be duplicated in other chromosome segments on the same or other linkage groups. Some of the At genes, which could not be genetically mapped because of lack of polymorphism, were assigned to their respective linkage groups by physical mapping. The presence of multiple copies of the A. thaliana gene cluster in the three Brassica genomes further establishes their complex nature, which results from extensive duplication and chromosomal rearrangement. In general, genetic distances between the At genes agreed with values expected for the physical distances determined in Brassica.

Aminopeptidases↗
PubMed1996

The comparison of geometric and electronic properties of molecular surfaces by neural networks: application to the analysis of corticosteroid-binding globulin activity of steroids.

It is shown how a self-organizing neural network such as the one introduced by Kohonen can be used to analyze features of molecular surfaces, such as shape and the molecular electrostatic potential. On the one hand, two-dimensional maps of molecular surface properties can be generated and used for the comparison of a set of molecules. On the other hand, the surface geometry of one molecule can be stored in a network and this network can be used as a template for the analysis of the shape of various other molecules. The application of these techniques to a series of steroids exhibiting a range of binding activities to the corticosteroid-binding globulin receptor allows one to pinpoint the essential features necessary for biological activity.

Drug Design↗