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Biomedical subjects

J Przybylski

Publications and source records attributed to J Przybylski.

At least 37 records · Page 2Linked to original sources

High renin arterial hypertension due to occlusion of the adrenal veins in the rat.

The direct adreno-renal vascular connection allows precise control of the kidney function by hormones produced by the adrenal gland, without any significant changes in their content in the whole blood. The purpose of the present study is to investigate the effect of the increased blood flow through the vascular network on the blood pressure. In twelve Wistar rats the central adrenal veins were ligated bilaterally. This procedure resulted in chronic increase in systolic blood pressure. This model of arterial hypertension is characterized by high plasma renin activity and normal aldosterone plasma concentration.

Adrenal Glands↗

Advances in the design of selective antagonists, potential tocolytics, and radioiodinated ligands for oxytocin receptors.

Despite intensive efforts over three decades in many laboratories, attempts to design peptide antagonists of oxytocin (OT) which are more selective for OT uterine receptors than for vasopressin (AVP), vasopressor V1a receptors, have met with only limited success. We will review the current status of the field and report on studies in our laboratories which have led to the design of highly potent non-selective and selective OT antagonists. Virtually all are more potent (2-6 fold) and a number are more selective (10-12 fold) than Atosiban, currently in clinical trial as a tocolytic agent. Many of these new published and unpublished OT antagonists are thus promising candidates for development as potential tocolytic agents for the prevention of pre-term labor. We also report on promising new radioiodinatable ligands for OT receptors. All the new OT antagonists are valuable new tools for studies on the physiological roles of OT and as probes for OT and AVP receptors.

Amino Acid Sequence↗

Effects of new somatostatin analogs on the cell proliferation of colonic crypts and colonic cancers in rats.

The antiproliferative activity of two new somatostatin (SS) analogs: ASS-51 and ASS-52 have been tested in this study. We assessed their ability to inhibit the DNA synthesis in normal colon crypt cells and in the cells of chemically (dimethylhydrazine)-induced colon cancer in the rats. The incorporation of bromodeoxyuridine (BrDU) into appropriate cell nuclei was used as an index of DNA synthesis. It was found that: 1) Only ASS-51 significantly decreases the colon crypt cell proliferation in the rat when compared to controls. Since both analogs were previously shown to inhibit GH release, these data indicate that the antiproliferogenic effect of ASS-51 is independent of the inhibition of GH release. 2) Both examined analogs did not significantly effect the BrDU incorporation into cell nuclei of chemically-induced colon cancer.

Adenocarcinoma↗

Potent V2/V1a vasopressin antagonists with C-terminal ethylenediamine-linked retro-amino acids.

We report the solid-phase synthesis and antagonistic potencies of 25 analogues (1-25) of [1-(beta-mercapto-beta,beta-pentamethylenepropionic acid),2-O-ethyl-D-tyrosine,4-valine]arginine-vasopressin (d(CH2)5D-Tyr(Et)2-VAVP) (A) and of the related Ile4 (D) and [D-Phe2,Ile4] (E) analogues, potent antagonists of the antidiuretic (V2-receptor) and of the vasopressor (V1a-receptor) responses to arginine-vasopressin (AVP). Six of these peptides (1, 13, 17, 19, 21, and 23) have the Pro-Arg-Gly-NH2 tripeptide side chain fully or partially replaced or extended by ethylenediamine (Eda). The remaining 19 peptides have L- or D-amino acids retrolinked to these six C-terminal Eda peptides. Peptides 1, 13, 17, and 19 all have the ring structure of (A). Their side-chain structures are as follows: 1, Eda; 13, Pro-Eda; 17, Pro-Arg-Eda; 19, Arg-Gly-Eda. Peptide 21 is the Pro-Arg-Eda analogue of D; peptide 23 is the Pro-Arg-Gly-Eda analogue of E. Peptide 2 is the retro-Arg analogue of 1. Its side-chain structure is Eda<--Arg. Peptides 3-6 are analogues of 2 which have the D-Tyr-(Et)2 residue replaced by L-Tyr(Et)2 (3), D-Phe2 (4), D-Ile2 (5), or D-Leu2 (6), respectively. Peptides 7-12 are analogues of 2 which have the C-terminal retro-Arg replaced in retrofashion by D-Arg (7), Gly (8), Orn (9), D-Orn (10), D-Lys (11), or Arg-Arg (12). Peptides 14-16 have D-Orn (14), D-Lys (15), and D-Arg (16) retrosubstituted to peptide 13. Peptides 18, 20, and 22 are the retro-Arg-substituted analogues of 17, 19, and 21, respectively. Peptides 24 and 25 have Val and D-Val in retrolinkage with 23, respectively. All 25 peptides were examined for agonistic and antagonistic potencies in AVP V2/V1a assays. With the exception of peptides 5 and 6, all exhibit potent anti-V1a antagonism, with anti-V1a pA2 values in the range 7.64-8.33.(ABSTRACT TRUNCATED AT 400 WORDS)

Amino Acid Sequence↗

Direct vascular connection between adrenal gland and kidney may play an important role in pathogenesis of hypertension.

A direct vascular connection between adrenal gland and kidney exists in various species. Thereby kidney function might be modified by the adrenal gland more precisely. In addition, the impact of adrenal hormones on the kidney function due to this circulatory 'by-pass' might be much stronger than judged from the relevant hormone concentrations in the circulating blood. Because overactivity of the sympatho-adrenal system is evident in essential hypertension we hypothesize that the adrenal-renal vascular connection plays an important role in the pathogenesis of arterial hypertension.

Adrenal Cortex Hormones↗

The aortic bodies of spontaneously hypertensive (SHR) and normotensive rats--a study concerning location and size.

The aortic bodies, including the right and left subclavian bodies and the superior aorticopulmonary bodies, were examined in inbred normotensive control rats (NCR) of the Wistar strain and in spontaneously hypertensive rats (SHR) of the OKAMOTO-AOKI strain. Paraganglia were found in all rats of either group. They were located near to the left common carotid artery and less frequently between the branching right subclavian and right common carotid artery. Superior aorticopulmonary bodies were rarely seen. No significant differences were found regarding the volume of individual aortic bodies when comparing these paraganglia in NCR and SHR. However, aortic bodies are more numerous in SHR and therefore the total volume of aortic body tissue per rat is significantly larger in this strain. There was good correlation between the total volume of aortic bodies and the total volume of carotid bodies in both strains of rats studied. These findings indicate, that the paraganglionic system as a whole is enlarged in SHR. This enlargement probably is caused genetically and not a result of increased blood pressure.

Animals↗

Carotid and aortic bodies in chronically anemic normotensive and spontaneously hypertensive rats.

Overactivity of the carotid body chemoreceptors along with the enlargement of chemoreceptor tissue were found in spontaneously hypertensive rats of Okamoto-Aoki strain (SHR). The purpose of the present study was to answer the question whether the aortic bodies were also enlarged in SHR. However, because aortic bodies, unlike carotid ones, are sensitive to oxygen content another question arose: do aortic bodies undergo hypertrophy in chronic anemia? Twenty-three spontaneously hypertensive rats of Okamoto-Aoki strain (SHR) and 24 normotensive Wistar rats (NCR) were maintained on low-iron food from the age of 3 weeks. In seven 10-week-old anemic SHR regular diet was substituted (transiently anemic SHR). Blood pressure measurements and hemoglobin were measured every second week. The animals were killed at the age of 18 weeks. Light microscopic studies of the carotid and aortic bodies were performed and volumes of chemoreceptor tissues were determined from serial sections. The eight SHR on low-iron diet exhibited lower hemoglobin concentration than their normotensive counterparts. In the anemic SHR blood pressure was lower than in control SHR, whereas blood pressure did not differ between the anemic and control NCR. Restoration of normal values of hemoglobin in the anemic SHR was followed by only a slight increase in blood pressure. The carotid bodies volumes were 2.5-3 times larger in the SHR than in NCR. The volumes of carotid bodies both of the SHR and NCR were influenced neither by blood pressure nor by hemoglobin concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

Anemia↗

[The first experience using C-D equipment in the surgical treatment of idiopathic scoliosis (preliminary report)].

The authors treated surgically 21 patients with scoliosis by intersegmental posterior spondylodesis with use of the Cotrel-Dubousset instrumetarium. The surgical method and results have been presented. The mean age of the patients was 14.6 years. The used method produced great correction (70 per cent) of scoliosis; its another equally important advantage is the possibility to restore physiological curvatures of the spine and removal of gibbus. The intra obtained operationally perfect internal frame stabilization of a corrected scoliotic segment of the spine enables standing positioning and mobilization of a patient several days after operation, securing the operated on child maximum of psychical comfort. The mean follow-up was 18 months.

Adolescent↗

Effect of alcohol upon arrhythmias following nonpenetrating cardiac impact.

The purpose of this study was to determine if alcohol worsens arrhythmias produced by nonpenetrating cardiac impact. Twenty-three dogs were studied. Twelve underwent nonpenetrating cardiac impact alone at 12 m/sec with a contact compression of 2 cm. Eleven underwent cardiac impact after having received intravenous alcohol (blood level of 197 +/- 37 mg/100 ml) (mean +/- SD). Three dogs experienced ventricular fibrillation immediately after impact and died: of these, two underwent impact alone and one underwent impact following ethanol. These three dogs were eliminated from the study. All of the dogs had some form of complex arrhythmia during the first 10 minutes of observation, the average cumulative duration of which during the first 10 minutes following trauma was greater among dogs that received ethanol. No complex arrhythmias other than ventricular premature contractions or ventricular tachycardia were observed after the first 10 minutes following impact. During the first 2 hours of observation following cardiac impact, dogs that received alcohol before trauma showed more single premature ventricular contractions (p less than 0.03), couplets (p less than 0.01), triplets (p less than 0.02), runs of 4-20 beats (p less than 0.05), and total number of premature ventricular contractions (p less than 0.05) than dogs that underwent trauma alone. Following the first 10 minutes, ventricular irritability increased with time until approximately 1 hour, and then there was a gradual reduction of the frequency of arrhythmias in both dogs that received alcohol and those that did not. In conclusion, nonpenetrating cardiac impact in dogs that previously received ethanol was associated with greater ventricular irritability than in dogs that underwent impact alone.

Animals↗

Peak aortic blood acceleration reflects the extent of left ventricular ischemic mass at risk.

Peak aortic blood velocity (Vel), peak acceleration (Acc), stroke volume (SV), and left ventricular (LV) ejection fraction (EF) have been used as noninvasive indicators of global LV performance. The purpose of this study was to determine which of these indices of LV performance relates best to the extent of LV ischemic mass at risk. Studies were performed in 24 open-chest anesthetized dogs. Acute ischemia was produced by occlusion of various levels of the left anterior descending and circumflex coronary arteries. LV ischemic mass, measured as a percent of total LV mass, was delineated by injection of Evans blue dye into the nonischemic zone. Acc and Vel were measured with continuous-wave Doppler ultrasound. EF was measured angiographically. All parameters were measured during a control period and within 6 minutes of coronary occlusion. The percent change during ischemia of each parameter relative to control (% delta) was calculated. The correlation coefficient between the percent ischemic mass at risk and % delta Acc was 0.88. It was 0.84 for % delta EF, 0.77 for % delta Vel, and 0.17 for % delta SV. These results indicate that among the various global indices of LV performance that have been used noninvasively, Acc correlates most closely with the extent of LV ischemic mass at risk.

Animals↗

Supernormal conduction in the accessory pathway of patients with overt or concealed ventricular pre-excitation.

It was recently shown that supernormal conduction in the diseased His-Purkinje system is more common than previously thought, and is always associated with prolongation of refractoriness. To assess whether supernormal conduction could also occur in the accessory pathway of patients with ventricular pre-excitation, 21 patients with manifestly prolonged refractoriness in the accessory pathway were studied. Under these conditions, programmed atrial stimulation revealed a phase of supernormal conduction in 16 (76%) of the 21. Therefore, what was believed to be a nonexistent or exceptional physiologic event was shown to be a rather common finding, at least under certain circumstances. Supernormal conduction occurred in all 7 patients with an anterograde refractory period of 480 to 980 ms, and in 5 of 10 patients with a refractory period greater than 1.0 second or with no anterograde conduction. Supernormal conduction could not be demonstrated in four patients with a refractory period less than or equal to 440 ms, but appeared in all four patients after the refractory period was prolonged by a rapid rate of stimulation or administration of ajmaline. The electrophysiologic changes underlying the occurrence of supernormal conduction in the accessory pathway are similar to those previously reported for the bundle branch system. The demonstration of supernormal conduction in the accessory pathway may uncover the presence of concealed ventricular pre-excitation. Supernormal conduction over the accessory pathway may facilitate a rapid ventricular response during atrial fibrillation, even if the refractory period is prolonged.

Heart Conduction System↗

Does excessive tissue oxygen supply contribute to the development of spontaneous arterial hypertension in rats?

Fifteen spontaneously hypertensive rats of the Okamoto strain and 14 normotensive Wistar rats were kept on low iron diet until 3 weeks old. Nine hypertensive and 10 normotensive rats fed regular diet served as controls. Hypertensive rats exhibited higher haematocrit and haemoglobin levels. Low iron diet produced a more pronounced decrease in the haemoglobin level in hypertensive than in normotensive rats, indicating increased iron turnover in the former group. Anaemia inhibited development of arterial hypertension in Okamoto strain rats whereas it did not affect blood pressure in normotensive rats. The results point to an important role of the blood oxygen carrying capacity for the development of spontaneous hypertension in rats.

Anemia↗

Efficacy of amiodarone during long-term treatment of malignant ventricular arrhythmias in patients with chronic chagasic myocarditis.

Oral amiodarone was administered to 24 patients with chronic chagasic myocarditis (CCM) and malignant ventricular arrhythmias. Control 24-hour Holter recordings revealed frequent ventricular premature beats (VPBs) (157 to 2572/hr; mean 714 +/- 125), multiform VPBs, and countless numbers of ventricular couplets in all patients, R-on-T phenomenon in 17 patients, and ventricular tachycardia in 21 patients. Amiodarone caused total and persistent suppression of ventricular couplets and tachycardia and greater than 93% reduction of VPB number in 22 patients, during a follow-up of 26.6 months (range 2 to 55 months). In 1 patient, ventricular couplets and tachycardia persisted despite the fact that a 98.2% reduction of VPB number was achieved. This latter patient was the only one in the whole group who experienced sudden death. The maximal antiarrhythmic effect was attained gradually after 3 to 26 weeks (mean 7.4). In four patients in whom treatment was discontinued after 3 to 12 months, the antiarrhythmic protection lasted 4 to 9 weeks. In nine patients the dose of amiodarone was 600 to 800 mg/day. In 15 patients the dose had to be increased to 800 to 1000 mg/day. Despite the presence of congestive heart failure in seven patients and intraventricular block in 17 patients, no limiting side effects were observed. Amiodarone proved to be extremely effective and safe against the most malignant ventricular arrhythmias of CCM.

Adult↗

Electrocardiographic changes evoked by ajmaline in chronic Chagas' disease with manifest myocarditis.

Conversion from Chagas' infection to chagasic myocarditis occurs slowly and the earliest signs of myocardial involvement are hard to define. To obtain new information on this difficult clinical problem, ajmaline was administered (1 mg/kg body weight intravenously) to 101 patients with Chagas' infection and to 46 patients without such infection (control group). In 3 patients in the control group left anterior hemiblock alone occurred whereas in the group with Chagas' infection, ajmaline caused the occurrence of right bundle branch block, left anterior hemiblock, or both, in 32 patients (31.6 percent), ventricular extrasystoles in 8 (7.9 percent) and ischemic ST-T changes in 7 (6.9 percent). Ajmaline may thus evoke the most typical electrocardiographic changes of chronic chagasic myocarditis in patients without signs of myocardial involvement or only minor nonspecific signs. A positive ajmaline test, defined in the present context as the occurrence of a fascicular block, ventricular arrhythmias or ischemic ST-T changes, may indicate the existence of localized areas of injured myocardial tissue, not enough to alter the electrocardiogram by itself, but able to give rise to severe abnormalities after exposure to the drug. The test may therefore be used as a nonspecific detector of myocardial damage, and thus may have a much broader scope of clinical application. In chronic Chagas' infection, the ajmaline test is a relatively simple and apparently safe procedure that may serve to unveil the earliest signs of chagasic myocarditis.

Adolescent↗

Usefulness of the ajmaline test in patients with latent bundle branch block.

Twelve patients were studied with intermittent bundle branch block whose conduction disturbance disappeared completely and could no longer be recorded even after provoked changes in heart rate. Premature atrial stimulation and atrial pacing at rapid rates were performed in nine patients; in none of these nine were these procedures able to evoke the complete bundle branch block pattern that all patients exhibited before the spontaneous normalization of conduction. In marked contrast, the administration of ajmaline (1 mg/kg body weight, intravenously in 90 seconds) caused the bundle branch block pattern to reappear in 10 (83.3 percent) of the 12 patients 30 to 120 seconds after the end of the injection, and in 11 patients (91.6 percent) when additional atrial stimulation was performed in 1 of the 2 "failures." This pharmacologic test was much more rapid and simple than electrophysiologic testing and it was noninvasive. Results of this study suggest that some form of subclinical fascicular injury was present (or had persisted) at a time when intraventricular conduction was persistently normal even though no significant physiologic alteration could be demonstrated by the atrial stimulation techniques. The ajmaline test may become a valuable tool for uncovering cases of latent bundle branch block and furthering our knowledge of the early natural history of intraventricular block.

Adult↗