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Biomedical subjects

M Péter

Publications and source records attributed to M Péter.

At least 19 recordsLinked to original sources

Liquid chromatographic enantioseparation of beta-blocking agents with (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate as chiral derivatizing agent.

The applicability of (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate [(R,R)-DANI] as a recently developed chiral derivatizing agent for the enantioseparation of a series of beta-blockers is described. The thiourea diastereomers formed were analyzed by reversed-phase high-performance liquid chromatography, mixtures of water and methanol or acetonitrile being used for elution. Conditions of derivatizations (temperature, reagent excess and reaction time) were optimized, and the effects of organic modifiers on the retention and separation were investigated; the diastereomers could readily be baseline separated with methanol-containing mobile phases with resolutions between 1.58 and 2.72.

Adrenergic beta-Antagonists↗

Effects of toxins Pi2 and Pi3 on human T lymphocyte Kv1.3 channels: the role of Glu7 and Lys24.

Pandinus imperator scorpion toxins Pi2 and Pi3 differ only by a single amino acid residue (neutral Pro7 in Pi2 vs. acidic Glu7 in Pi3). The binding kinetics of these toxins to human Kv1.3 showed that the decreased ON rate (k(ON) = 2.18 x 10(8) m(-1)sec(-1) for Pi2 and 1.28 x 10(7) m(-1)sec(-1) for Pi3) was almost entirely responsible for the increased dissociation constant (K(d)) of Pi3 (K(d) = 795 pm) as compared to Pi2 (K(d) = 44 pm). The ionic strength dependence of the association rates was exactly the same for the two toxins indicating that through-space electrostatic interactions can not account for the different ON rates. Results were further analyzed on the basis of the three-dimensional structural models of the toxins. A 3D structure of Pi3 was generated from the NMR spectroscopy coordinates of Pi2 by computer modeling. The Pi3 model resulted in a salt bridge between Glu7 and Lys24 in Pi3. Based on this finding our interpretation of the reduced ON rate of Pi3 is that the intramolecular salt bridge reduces the local positive electrostatic potential around Lys24 resulting in decreased short-range electrostatic interactions during the binding step. To support our finding, we constructed a 3D model of the Ser-10-Asp Charybdotoxin mutant displaying distinctly reduced affinity for Shaker channels. The mutant Charybdotoxin structure also displayed a salt bridge between residues Asp10 and Lys27 equivalent to the one between Glu7 and Lys24 in Pi3.

Amino Acid Sequence↗

Multiple binding sites for melatonin on Kv1.3.

Melatonin is a small amino acid derivative hormone of the pineal gland. Melatonin quickly and reversibly blocked Kv1.3 channels, the predominant voltage-gated potassium channel in human T-lymphocytes, acting from the extracellular side. The block did not show state or voltage dependence and was associated with an increased inactivation rate of the current. A half-blocking concentration of 1.5 mM was obtained from the reduction of the peak current. We explored several models to describe the stoichiometry of melatonin-Kv1.3 interaction considering one or four independent binding sites per channel. The model in which the occupancy of one of four binding sites by melatonin is sufficient to block the channels gives the best fit to the dose-response relationship, although all four binding sites can be occupied by the drug. The dissociation constant for the individual binding sites is 8.11 mM. Parallel application of charybdotoxin and melatonin showed that both compounds can simultaneously bind to the channels, thereby localizing the melatonin binding site out of the pore region. However, binding of tetraethylammonium to its receptor decreases the melatonin affinity, and vice versa. Thus, the occupancy of the two separate receptor sites allosterically modulates each other.

Antibodies, Monoclonal↗

Is every sharply defined, symmetrical, necrotic-demyelinating lesion in the corpus callosum an actual manifestation of Marchiafava-Bignami disease?

Neuroimaging of a 75-year-old lady demonstrated the characteristic pathological features of the Marchiafava-Bignami disease (MBD), which develops usually in chronic alcoholics. The onset of the neurological symptoms and signs were abrupt and similar to those seen in common ischemic vascular lesions. Our patient denied that she had consumed alcoholic beverage during her life. Laboratory results showed her liver enzymes were not elevated and a subsequent abdominal ultrasound examination revealed no liver pathology. The attack responded fairly well to anti-ischemic therapy and a complete recovery was observed within a week. In this sense, her pathology cannot be considered as a true MBD in spite of the presence of the CT and MRI findings of MBD. Our case seems to show that the CT and MRI findings in MBD are not specific because new imaging procedures reveal edematous, necrotic lesions that may have the appearance of MBD.

Aged↗

[CT-guided percutaneous drainage in the treatment of acute necrotizing pancreatitis].

The authors analysed the results of the treatment of 24 patients with acute necrotizing pancreatitis. Besides intensive and operative treatment prophylactic antibiotics, early naso-jejunal feeding, CT guided percutaneous peripancreatic drainage are favourable to avoid septic complications and to postpone the first operation. In 11 patients percutaneous drainage was performed. Using percutaneous drainage three patients (33.3%) recovered without operation, the mean drainage time was 23.4 days. The first operation could be postponed in the other 8 patients after percutaneous drainage. No complications occurred as result of the interventions, although in one patient the drain slipped out spontaneously. Due to the complex treatment the total mortality rate was 12.5%.

Adult↗

[The role of percutaneous radiologic interventions in the treatment of pancreatic pseudocysts].

Authors evaluate the indications and results of percutaneous puncture and drainage of pancreatic pseudocysts. The interventions were performed in 20 patients. The first line treatment is usually surgical. Percutaneous drainage or aspiration is suggested if the patient is symptomatic, the size of pseudocyst is between 3 and 6 cms and when it can be punctured using radiological procedures, without the risk of damaging other organs. Previous peripancreatic operation, high-risk surgical intervention and the refusal of the operation by the patient should also be considered. Percutaneous drainage is an alternative method for the treatment of pancreatic pseudocysts. The advantages of this procedure are: It is minimally invasive, complications are rare and reintervention is possible. Disadvantage is high risk of recurrence.

Adult↗

Blockage of human T lymphocyte Kv1.3 channels by Pi1, a novel class of scorpion toxin.

Using the patch-clamp technique we determined that Pandinus imperator toxin Pi1, a recently described peptide toxin having four disulfide bridges instead of the usual three in scorpion toxins, blocked Kv1.3 channels of human T lymphocytes from the extracellular side with a 1:1 stoichiometry. Kv1.3 block was instantaneous and removable with toxin-free extracellular solution. The toxin did not influence activation or inactivation of the channels. We found that Pi1 blocked Kv1.3 with less affinity (K(d) = 11.4 nM) than the structurally related three disulfide bridge containing toxins Pi2 (50 pM) and Pi3 (0.5 nM). The fourth disulfide bridge in Pi1 had no influence on the channel binding ability of the toxin; the less effective block was due to differences in amino acid side chain properties at positions 11 and 35.

Amino Acid Sequence↗

[Clinical evaluation of local lipiodol chemoembolization therapy in primary and secondary hepatic tumors].

The authors treated with locoregional lipiodol chemoembolization 32 patients suffering from primary and secondary liver malignancies. They present the clinical results of the 22 patients who received at least 2 treatments. Distribution of patients: 17 men, 5 women, mean age 56.2 (43-80) years. Seven patients suffered from primary liver carcinoma; regarding the Child's staging of the tumors 4 patients were in Child A, 3 patients in Child B. In 15 cases the treatment indication was secondary liver cancer. The primary tumors in these secondary liver cancer cases were: one case lung cancer, 11 colon (2 cases rectum) cancer, 2 cases pancreas cancer, one case gastric carcinoma. The 22 patients received in total 97 cycles of therapy. After the selective catheterisation of the hepatic artery adriamycin, mitomycin C, 5-fluorouracil or lipiodol was administered. During the mean follow up time of 9 months (3-15 months) remission could be observed in 6/22 patients. The side effects were preventable or medically treatable. It can be concluded that in the case of well-selected cases of non-resectable liver malignancies local chemoembolization could be beneficial, as it could slow down the progression of the underlying disease with the maintainment or even improvement of the quality of life.

Adult↗

Application of (1S,2S)- and (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate to the indirect enantioseparation of racemic proteinogenic amino acids.

The application of (1S,2S)- or (1R,2R)-1,3-diacetoxy-1-(4-nitrophenyl)-2-propylisothiocyanate as a new chiral derivatizing agent for the resolution of compounds possessing an amino group is described. The reagent is easily accessible in both enantiomeric forms after a simple two-step synthesis. Its applicability was demonstrated on the example of the resolution of a series of alpha-amino acids. The diastereomeric thiourea derivatives produced were separated by reversed-phase high-performance liquid chromatography. The effects of pH, temperature and reagent excess on the derivatization kinetics were investigated, as were the effects of pH and organic modifier on the separation.

Amino Acids↗

[Results of surgical treatment of liver abscess, with special emphasis of percutaneous puncture and drainage].

Authors present 5 cases of liver abscess treated with US or CT guided percutaneous puncture and/or drainage performed in cooperation of the 2nd Surgical Department and the Radiological Department of the University of Debrecen. They analyse the indications and results of this method. They also include the results of twelve liver abscesses treated surgically. For one or a small number of liver abscesses (Bigger than 5 cm) they prefer percutaneous drainage combined with systematic antibiotic treatment if the condition is not complicated by other surgical diseases, and if the abscesses are accessible for radiological intervention. All patients recovered without recurrence during a one-year follow-up period. The main advantages of this method are smaller trauma and fewer complications.

Adult↗

Study of diastereomeric thioureas formed with a new chiral derivatizing agent.

(1S,2S)-1,3-Diacetoxy-1-(4-nitrophenyl)-2-propyl isothiocyanate ((S,S)-DANI) was recently introduced as a new chiral derivatizing agent for the enantioseparation of amino compounds. In the present study, diastereomeric derivatives of racemic amino acids were formed with (S,S)-DANI. The thioureas produced were distinguished by means of infrared spectroscopy, theoretical calculations and high-performance liquid chromatography. The differences observed between the corresponding diastereomers by the independent methods are considered to prove the applicability of the new reagent in the field of enantiomer separation.

Amino Acids↗

[Diagnostic possibilities in gastric leiomyoma in relation to two of our cases].

Two cases of rare, benignant gastric tumors are reported. The suggest that while in the diagnosis of tumors with a mucous membrane involvement endoscopy has doubtless a leading role, tumors not infiltrating the mucous membrane are usually better recognizable by radiological (ultrasonography, computer tomography and double contrast x-ray) methods. An appropriate diagnosis followed by surgical removal of the tumor might result in a complete healing of the patient.

Aged↗

[Our experience with Transjugular Intrahepatic Portosystemic Shunt (TIPS)].

The transjugular intrahepatic portosystemic shunt is a relatively new interventional procedure for the treatment of portal hypertension. It helps to stop the hemorrhage from varices. Decreases the risk of rebleeding and the quantity of ascites. 32 patient underwent the intervention from the May of 1995 until October of 1998. Majority of cases belong to Childs'B and C type. In the anamnesis there were 24 alcoholic cirrhosis. Shunt patency, complications and survival were analyzed. TIPS was successfully placed in 27 patients (84%). Portocaval pressure gradient decreased from 22 mmHg to 10.3 mmHg. There was no treatment related mortality. The average follow up was 14 months. In two patients the stents are patent for 36 months. Two stents became stenotic and there were nine occlusions within three years. Hepatic encephalopathy occurred in two cases. The TIPS is a safe, alternative interventional radiological therapy in the cure of portal hypertension without the mortality and morbidity of an open surgical procedure. By the use of TIPS the portosystemic gradient decrease successfully and can be ruled.

Adult↗

[Diagnosis of Meckel diverticulum, containing ectopic gastric mucosa", by studying small bowel passage].

Radiological diagnosis of Meckel diverticulum is a difficult task. Here we report a patient with hereditary sphaerocytosis who complained of a chronic periumbilical pain and in whom antegrade barium enema suggested Meckel diverticulum. The diagnosis had been proven both surgically and histologically. This observation indicates that so called traditional x-ray still has its role even in the era of modern (and expensive) radiology.

Adult↗

[Study of the contractility of the gallbladder by ceruletide infusion cholescintigraphy after litholysis].

Twenty-six randomly selected patients 2-6 years (mean: 3.5) after rapid percutaneous catheteric litholysis at the Radiological Department were investigated by quantitative Ceruletide cholescintigraphy in this pilot study. The average EF of the patients with recurrent gallstones (Group II) was lower (55 +/- 23%) than that of the patients without stones (69 +/- 23%) (Group I). The authors conclude that this scintigraphic method could help not only to select the best method to make patient stonefree but has an important role in forecasting the prognosis of gallstone recovery after litholytic therapy.

Ceruletide↗

Pandinus imperator scorpion venom blocks voltage-gated K+ channels in human lymphocytes.

Using the patch-clamp technique, we determined that Pandinus imperator scorpion venom blocked whole-cell n-type K+ currents in human peripheral blood lymphocytes in a dose-dependent manner with Kd = 0.02 microgram/ml. K+ channel block was instantaneous and removable by washing with venom-free extracellular solution. The venom-induced block was independent of membrane potential. The venom did not influence activation and inactivation kinetics of the K+ channels, however, accelerated recovery from inactivation. Purified peptides Pi1, Pi2, and Pi3 from the P. imperator venom powerfully blocked Kv1.3 channels in human lymphocytes with Kd values of 9.7 nM, 50 pM, and 0.5 nM, respectively. Flow cytometric membrane potential measurements with the oxonol dye showed that Pi2, the most effective peptide toxin of the P. imperator venom, depolarizes human lymphocytes in accordance with its K+ channel blocking effect.

Barbiturates↗

Postoperative chemoembolism treatment of primary and metastatic malignant hepatic tumours.

Between 1992 and 1996 62 patients were operated for primary malignant and metastatic hepatic tumours. After the operation 31 patients received cytostatical treatment, 9 patients were treated with the method of chemoembolism. 46 patients are alive 30.7 (5-54) months after the operation. 9 patients died 12.5 (3-27) months after the resection of the liver. Authors have favourable experiences on the treatment of chemoembolism.

Antineoplastic Combined Chemotherapy Protocols↗