Biomedical subjects

A Kálmán

Publications and source records attributed to A Kálmán.

At least 19 recordsLinked to original sources

PubMed2002

5-Alpha- and 5-beta-2-deoxyintegristerone A, a 5-alpha and 5-beta isomer pair of ecdysteroids isolated from the Silene genus.

5-Alpha-2-deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were isolated from the aerial parts of Silene italica ssp. nemoralis (Waldst. and Kit.) Nyman using a specific combination of absorption column chromatography, preparative thin-layer chromatography and preparative HPLC. Both normal-phase and reversed-phase modes of HPLC were employed for isolation. Structural elucidation of 5-alpha-2-deoxyintegristerone A was completed by X-ray diffraction. Both 5-alpha-2-deoxyintegristerone A and 5-beta-2-deoxyintegristerone A were firstly isolated from this plant. We propose that 5-alpha-2-deoxyintegristerone A is not an artifact but an integral part of the ecdysteroid spectrum of Silene italica ssp. nemoralis (Waldst. and Kit.) Nyman.

Caryophyllaceae↗

PubMed2002

The use of axillary skin crease incision for thoracotomies of neonates and children.

UNLABELLED: Because of the complications due to "standard" postero-lateral thoracotomy, i.e. winged scapula, scoliosis etc., different muscle-sparing approaches have been published. In 1998 Bianchi et al published their work on axillary skin crease incision for neonates, primarily for the treatment of oesophageal atresia. AIM OF THE STUDY: To assess the usefulness of axillary skin crease incision in paediatric surgery. METHODS: Data of 26 cases with axillary skin crease incision were reviewed and the results compared to those of postero-lateral incisions. RESULTS: Axillary skin crease incision in both neonates and children (up to the age of 15 years) was used to treat both pulmonary and mediastinal lesions and both benign and malignant diseases. The authors performed 17 operations in neonates (8 oesophageal atresia with tracheo-oesophageal fistula, 8 patent ductus arteriosus, 1 congenital cystic adenomatoid malformation) and 9 operations in children (3 neuroblastoma, 1 teratoma, 5 pulmonary operations including lobectomies). The authors were able to perform all operations with unrestricted access through the axillary skin crease incision when the 3rd or 4th intercostal space was necessary for the thoracotomy. The authors compared patients operated with oesophageal atresia through an axillary skin crease incision with patients operated through a postero-lateral incision - seven neonates each. There were no significant differences in the results regarding duration of procedure, duration of postoperative ventilation or the incidence of anastomosis stricture. CONCLUSIONS: Although further long-term studies are necessary to evaluate the axillary skin crease incision, the authors believe that axillary skin crease incision should become the standard method for 3rd and 4th intercostal space thoracotomies in neonates and children.

Adolescent↗

PubMed2001

Basic forms of supramolecular self-assembly organized by parallel and antiparallel hydrogen bonds in the racemic crystal structures of six disubstituted and trisubstituted cyclopentane derivatives.

A selection of stereoisomeric 2-hydroxy-1-cyclopentanecarboxamides, a 4-tert-butyl derivative and three tert-butyl derivatives of the respective carboxylic acid were subjected to X-ray crystallography. The optically active molecules (I)--(VI) form racemic crystals. Each racemic structure is basically determined by two intermolecular hydrogen bonds of O--H...O==C--XH and O==C--X--H...OH types (X = O, NH). The partially similar patterns of close packing observed reflect five basic forms of supramolecular self-assembly. In the racemic crystals of chiral molecules, there are homo- and heterochiral chains of molecules formed by the principal (O--H...O==C) hydrogen bonds. These chains assemble either in a parallel or antiparallel mode. The parallel homochiral chains (hop) observed in structure (II), (1R*,2R*)-2-hydroxy-1-cyclopentanecarboxamide, demand the polar space group Pca2(1), while the parallel heterochiral chains (hep) are organized in antiparallel layers with space group P2(1)/n in structure (VI), (1R*,2S*,5R*-5-tert-butyl-2-hydroxy-1-cyclopentanecarboxylic acid). Heterochiral chains in an antiparallel array (hea) are found in (I), (1R*,2S*)-2-hydroxy-1-cyclopentanecarboxamide, and (V) [(1R*,2S*4S*)-4-tert-butyl-2-hydroxy-1-cyclopentanecarboxylic acid, space group P2(1)/c]. Structures (IV), (1R*,2S*,4R*)-4-tert-butyl-2-hydroxy-1-cyclopentanecarboxylic acid, and (III), (1R*,2R*,4S*)-4-tert-butyl-2-hydroxy-1-cyclopentanecarboxamide, reveal that homochiral chains in an antiparallel array (hoa; cross-linked by heterochiral dimers held together by the second hydrogen bonds) can be formed by either translation (space group P1) or a screw axis (space group P2(1)/c). These alternatives are denoted hoa1 and hoa2. Similarly, within each pattern (hea, hep and hop) two slightly different alternatives can be expected. The partial similarities in the identified five patterns of hydrogen bonding are described by graph-set notations. Structures (I), (IV) and (V) can be characterized by a common supramolecular synthon, while the highest degree of similarity is shown by the isostructurality of (I) and (V).

Journal Article↗

PubMed2001

Hydrogen-bonded hexagonal and pseudo-hexagonal grid motifs in supramolecular cobalt(II) and nickel(II) cupferronato complexes incorporating neutral N-donors with intermolecular NH2 connectors and solvent molecules.

The cobalt(II) and nickel(II) cupferronato (N-nitroso-N-phenylhydroxylaminato) mixed-ligand complexes of 2-aminopyridine (2-NH(2)py) [Co(PhN(2)O(2))(2)(2-NH(2)py)(2)] (1), [Ni(PhN(2)O(2))(2)(2-NH(2)py)(2)] (2) and 2,6-diamino-4-phenyl-1,3,5-triazine (dpt) [Co(PhN(2)O(2))(2)(dpt)(2)].[Co(PhN(2)O(2))(2)(EtOH)(2)] (3) have been synthesized and characterized by X-ray diffraction analysis. The cobalt (1) and nickel (2) complexes are isostructural. The crystal lattice of (3) contains different neutral cobalt(II) complexes [Co(PhN(2)O(2))(2)(dpt)(2)] (3a) and [Co(PhN(2)O(2))(2)(EtOH)(2)] (3b). Molecules of (1)-(3) contain octahedral metal centres with all-cis-(1) and -(2) and all-trans-(3) disposal of the ligands. Intramolecular N-H.O hydrogen bonding between the NH(2) groups and the O atom of the cupferronato anion can be observed in (1)-(3). Intermolecular N-H.O and N-H.N interactions between symmetry-related molecules of (1) and (2) led to hexameric aggregates which connect through common edges into a two-dimensional supramolecular network of hexagonal-grid type. In complex (3) the self-complementary dpt units of the (3a) molecules are maintained by intermolecular N-H.N hydrogen bonds, generating infinite chains. These (3a) chains are crosslinked by the (3b) subunits via N-H.O and O-H.N hydrogen bonds, thus completing the parallel two-dimensional supramolecular network consisting of pseudo-hexagonal-grid sheets. In each crystal structure the two-dimensional supramolecular networks are controlled by both hydrogen bonds and pi.pi stacking interactions.

Journal Article↗

PubMed2000

The analysis and crystallographic characterization of 20-hydroxyecdysone.

20-Hydroxyecdysone (20E) is an insect molting hormone that is also widely spread in various plants. Many chromatographic methods can be used to identify and/or determine 20E content in samples of biological origin and various spectroscopic methods serve to identify its structural elements. We have utilized X-ray crystallography to reveal the stereostructures of 20E. Our data demonstrates that 20E exists in two different crystalline forms that are both orthorhombic modifications. One form is homo-molecular, with a limited freedom of internal rotation of the side chain around the C23-C24 bond and the other, which is a clathrate formed with methanol and water, which minimize the conformational freedom of the side chain.

Animals↗

PubMed1999

Volumetric measure of isostructurality.

The numerical descriptors of isostructurality are critically reviewed and to overcome their limitations a new volumetric measure is proposed. It is defined as the percentage ratio of the overlapping volume of molecules in the analyzed structures to the average of the corresponding molecular volumes. For the calculation of this index a numerical approach is presented, which is also capable of treating disordered structures. The use of isostructurality calculations is demonstrated using a series of examples. Homologous 9-alkylthiophenanthrenes are used as simple illustrations of the necessity and applicability of the new descriptor. The structural changes in the inclusion compounds of 5-methoxysulfadiazine with chloroform, dioxane and tetrahydrofuran are analyzed and rationalized with the aid of isostructurality indices. The diverse relationships among a series of helical tubuland diols cocrystallized with simple phenols are also characterized. The modifications in molecular and crystal structures are correlated with the calculated degree of isostructurality.

Journal Article↗

PubMed1999

On the polymorphism of a sapogenin monohydrate induced by different rotations of water molecules.

The structure of 1beta,3beta,11alpha-trihydroxyspirosta-5,25(27)-diene (C(27)H(40)O(5); a steroidal sapogenin) isolated from Helleborus serbicus Adam 1906 (Ranunculaceae) and crystallized from absolute ethanol as a monohydrate (melting point 519-522 K) had been characterized by two symmetry-independent binary (steroid-water) layers, cross-linked by hydrogen bonds [Kálmán et al. (1985). Acta Cryst. C41, 1645-1647]. Recently, a novel monohydrate was crystallized again from absolute ethanol (source: Helleborus multifidus subspecies serbicus) with a somewhat higher melting point of 525-526 K. X-ray analysis of these crystals [Argay et al. (1998). Acta Chim. Hung. 135, 449-456] revealed a novel polymorph (hereinafter denoted polymorph B), which is also built up by two binary layers of C(27)H(40)O(5) and H(2)O, but in which the relative position of these layers differs from that found in the first modification (polymorph A). Comparing the two polymorphs, layers of one type are found to be similar, displaying identical hydrogen bonding, whereas layers of the second type differ with respect to the orientations adopted by the water molecules; these orientations also differ from those in the layers of the first type. Consequently, by these water rotations, hydrogen bonds, at least partly, are reversed. This leads to two different close packings: in form A four consecutive layers are cross-linked by two homomolecular (hydroxyl.hydroxyl and water.water) hydrogen-bond pairs, while in B there are only heteromolecular hydroxyl.water bonds. These hydrogen-bond dissimilarities together with the differences in the weak CH.X etc. interactions explain the greater stability of the higher melting-point form B.

Journal Article↗

PubMed1999

Stereochemistry and enantiomeric purity of a novel anxiolytic agent, deramciclane fumarate.

The synthesis, stereostructure, and enantiomeric separation by chromatography of a new, chiral anxiolytic agent, deramciclane fumarate (2, (-)-[1R,2S,4R]-2-(2-dimethylaminoethoxy)-2-phenyl-1,7, 7-trimethylbicyclo[2.2.1]heptane fumarate, EGIS-3886), is described. The optical antipode and the racemate of compound 2 were also prepared. The structure was determined by single crystal X-ray diffraction analysis. The enantiomeric separation was accomplished by HPLC on Chiralcel OD (250 x 4.6 mm; 10 microm) and hexane-ethanol (99.5:0.5) as mobile phase at room temperature. The enantiomeric purity of the synthesized drug substance proved to be very high (>99. 9%). Some statements published earlier on the stereostructure of deramciclane fumarate are critically discussed.

Anti-Anxiety Agents↗

PubMed1996

Kinetic study on the cis-trans isomerization of peptidyl-proline dipeptides.

The equilibrium and kinetic parameters of cis-trans interconversion of dipeptides containing peptidyl-proline moiety were investigated using the in-column incubation method with both CZE and HPLC and the ad hoc dissolution method. The use of the latter was possible because the conformational make-up of the solid peptides, and consequently of their ad hoc solution, was sufficiently different from that of the solution at equilibrium. This method with 1H-NMR and CZE analyses yielded very similar results for the cis-trans isomerization of Phe Pro in aqueous sodium borate, pH 8.4, at 10 degrees C with an average value of 0.34 and 6.6 x 10(-5) s-1 for the equilibrium and rate constant, respectively. The in-column incubation method is performed by CZE or HPLC so that the conformers are separated in the first half of the column and then incubated in column where they interconvert and reach equilibrium. Subsequent separation in the second half of the column yielded four peaks. Thus by measuring the conformer composition as a function of the reaction time, the rate constant can be evaluated. The forward rate constant of 1.42 x 10(-4) s-1 determined by the CZE in-column incubation method for Phe-Pro isomerization at 10 degrees C was twice of the value obtained by the ad hoc dissolution method. It is believed that the inner wall of fused-silica capillaries has a catalytic effect on the isomerization. Computer simulation was also employed to gain further insight on the catalytic activity of the capillary inner wall on such isomerization. Whereas the experimental and simulation profiles of Phe-Pro in aqueous borate buffer, pH 8.4, with a 37 cm long capillary were in excellent agreement, a four times faster interconversion rate had to be used to match the experimental profile obtained with a 57 cm long capillary under otherwise identical conditions. The catalytic effect of the octadecyl silica stationary phase on the isomerization was confirmed by the in-column incubation method with HPLC. The overall rate of the cis-trans isomerization of Phe-Pro, which entails the reaction both on the stationary phase and in the mobility phase, was about six times faster at 0 degree C than the rate measured by NMR in free solution using the mobile phase containing 65% (v/v) sodium phosphate, pH 6.5, and 35% (v/v) methanol. The results presented here serve as a caveat that the effect of the wall in CZE or the stationary phase in HPLC on the reaction cannot be ignored.

Chromatography, High Pressure Liquid↗

PubMed1996

[Neonatal primary hyperparathyroidism].

The authors report on a case of severe primary hyperparathyroidism with clinical signs from birth. The boy was admitted because of poor somatomental development, hypotony, hepatosplenomegaly and osseous abnormalities, resembling those of rachitis. Laboratory data showed the typical findings of primary hyperparathyroidism. The authors performed parathyroidectomy with simultaneous heterotopic parathyroid tissue autotransplantation. Histology revealed parathyroid chief cell hyperplasia. Because of the hypercalcaemia and clinical signs persisting after the operation they removed the parathyroid autografts. Since this later was ineffective they performed a left sided neck dissection on the side of the excessive parathormone production. The child became hypocalcaemic necessitating calcium and vitamin D administration. He is now 17 months after the last operation. His somatomental development is accelerated. In connection with the case the authors surveyed the literature of this rare entity.

Humans↗

PubMed1996

Isolation and identification of peptide conformers by reversed-phase high-performance liquid chromatography and NMR at low temperature.

Peptide conformers with one or more rotationally hindered peptide bonds due to the presence of proline and/or another N-substituted amino acid residue in the molecule were separated by reversed-phase chromatography at low temperatures, isolated and identified by NMR. The scope of this investigation included the cis-trans isomers of the dipeptides Leu-Pro, Phe-Pro and Tyr-Pro as well as conformers of opioid peptides containing proline and/or the proline-like Tic (1,2,3,4-tetrahydro-isoquinoline-3-carboxylic acid) residues: Tyr-Pro-Phe (beta-casomorphin 1-3 fragment), Tyr-Tic-Phe-Phe, Try-Pro-Phe-Pro-Gly (beta-casomorphin-5), Tyr-Tic-Phe-Phe-Val-Val-Gly-NH2 and Tyr-Tic-Phe-Gly-Tyr-Pro-Ser-NH2. Chromatography with micropellicular and totally porous octadecylated silica stationary phases and aqueous methanol under isocratic elution conditions resulted in well separated peaks of the rotational isomers at sufficiently low temperatures. Preparative RP-HPLC was carried out with eluents containing water and methanol, both deuterated, and the effluent fractions containing each isomer were collected for further investigation. The conformational states of the peptide isomers upon separation were conserved by storing the effluent fractions in liquid nitrogen. The Leu-Pro, Phe-Pro, Tyr-Pro and Tyr-Pro-Phe conformers were identified by one- and two-dimensional NMR spectroscopy at -15 degrees C. Upon comparing the NMR spectra of the isomers, for these peptides the retention order of the conformers was unambiguously established: in each case the trans, conformer is eluted before the cis conformer. On the basis of NMR data obtained the beta-casomorphin-5, which contains two proline residues, the elution order of its four conformers was established by NMR spectroscopy of the fractions obtained by RP-HPLC at low temperature as trans-trans (least retained), trans-cis, cis-cis and cis-trans (most retained).

Amino Acid Sequence↗

PubMed1996

[Saturated heterocyclic compounds. 216 (1). Synthesis, structure and ring opening of trans-perhydro-1,4-benzoxazepin-3-one derivatives].

trans-Perhydro-1,4-benzoxazepin-3-ones 2a-e were synthesized and transformed to condensed-skeleton perhydro-trans-1,4-benzoxazepines 3a,b, the thiones 4a,b, the urea derivatives 5a,b, and N-acylated compounds 6a-e. Compounds 6b,d were ring-opened by hydrochloride acid in ethanol to yield trans-2 (1-carbethoxyethoxy)-1-(acylaminomethyl)-cyclohexane derivatives 7b,d. The 1H- and 13C-nmr investigation and X-ray analysis of 5b and 6c,d proved that the expected N-acylated derivatives were formed and that both rings of the annolated compounds have a chair conformation.

Acetylation↗

PubMed1995

Capillary zone electrophoresis at subzero temperatures. I. Separation of the cis and trans conformers of small peptides.

The cis-trans conformers of two dipeptides, Phe-Pro and Leu-Pro, and two opioid heptapeptides containing one or two proline residues were separated by capillary zone electrophoresis (CZE) in borate buffer at low temperatures down to -17 degrees C. At temperatures near ambient, the relaxation time of the cis-trans isomerization is on the time-scale of minutes for the dipeptides and thus commensurate with the migration times in CZE under usual operating conditions. The conformers of both dipeptides could be separated with baseline resolution below 10 degrees C in neat aqueous 100 mM sodium borate (pH 8.4). The conformer peaks on the electropherograms were identified by using authentic samples of the cis and trans forms of Phe-Pro and Leu-Pro that were obtained by reversed-phase HPLC at 0 degree C, validated by NMR spectroscopy and stored in liquid nitrogen. The interplay of the electrophoretic migration and on-column isomerization reaction in CZE of Phe-Pro under various conditions was analyzed in the light of the Damköhler number (Da). The results showed that besides employing low temperature increasing the voltage and/or decreasing the capillary length also reduce the magnitude of Da to bring about the separation of interconverting species. In this work the use of low temperature in this work was preferred due to the experimental simplicity. The separation of cis-trans conformers of two opioid heptapeptides was carried out by CZE at subzero temperatures with aqueous sodium borate containing 23% (v/v) glycerol at pH* 11.3 as measured with a glass electrode. The two conformers of Tyr-Pro-Phe-Asp-Val-Val-Gly-NH2 were baseline separated at -12 degrees C and the four conformers of Tyr-Pro-Phe-Gly-Tyr-Pro-Ser-NH2 due to the presence of two peptidyl-proline bonds in the molecule, were also resolved at -12 degrees C. From the electrophoretic mobilities, the hydrodynamic radii of the cis-trans conformers of the dipeptides Phe-Pro and Leu-Pro were estimated. In both cases, the trans isomers had 1.3 times greater Stokes radii than the cis conformers. This agrees with the observed migration order and molecular modeling results. The hydrodynamic radii of the Phe-Pro conformers were smaller than those of the Leu-Pro isomers despite the lower molecular mass of the latter. The results demonstrate that CZE is suitable for measuring certain molecular properties and suggest that the methods introduced here are applicable to the study of other systems of interconverting conformers.

Amino Acid Sequence↗

PubMed1995

[The value of ultrasonic diagnosis in acute appendicitis].

The diagnostic accuracy and practical value of graded compression ultrasound was evaluated in 298 patients admitted for ultrasound examination because of having suspected appendicitis by surgeons. The result of the ultrasound was considered to be positive, if the inflamed appendix, larger, than 6.5 mm in outer diameter or an abscess was depicted. Of the 99 pathologically proven cases of acute appendicitis ultrasound was positive in 94, that is the sensitivity was 94.9%. The diagnostic accuracy and specificity were 96.3% and 97.9%. The predictive value of a positive test was 95.9%, and was 97.5% of a negative one. In the group of patients under 18 years (140 patients) sensitivity, specificity and diagnostic accuracy were 93.3%, 96.3% and 95% respectively. The use of ultrasound helped many patients to earlier operation and reduced considerably the negative laparotomy rate. The routine use of ultrasound in the diagnosis of appendicitis especially if the clinical presentation is equivocal, complements usefully the clinical signs and increases diagnostic accuracy.

Acute Disease↗

PubMed1995

Structure-activity relationships of dermorphin analogues containing N-substituted amino acids in the 2-position of the peptide sequence.

A series of dermorphin analogues containing an N-alkylated amino-acid residue Xaa in the 2-position of the peptide sequence was synthesized (Xaa = N-methylalanine, proline, pipecolic acid, N-methylphenylalanine, 1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid [Tic]). These peptides have the potential of assuming a cis Tyr1-Xaa2 peptide bond. Their in vitro opioid activity profiles were determined in mu- and delta-receptor-representative binding assays and bioassays. Aside from [D-Pro2]dermorphin, all analogues showed high affinity for mu- and/or delta-opioid receptors. Whereas most compounds were found to be full mu-agonists in the guinea pig ileum (GPI) assay, [Tic2]dermorphin (compound 7) was a partial mu-agonist. Replacement of Gly4 in 7 with Phe resulted in an analogue (8) with weak mu-antagonist activity. Furthermore, analogues 7 and 8 both were potent delta-antagonists (Ke = 3-40 nM) against the delta-agonists Leu-enkephalin, DPDPE and deltorphin I in the mouse vas deferens (MVD) assay. Compound 3, containing L-Pro in the 2-position, turned out to be one of the most mu-receptor-selective linear dermorphin analogues reported to date. Low-temperature HPLC experiments using micropellicular octadecyl silica as stationary phase revealed conformational heterogeneity of the dermorphin analogues which was ascribed to cis-trans isomerization around the Tyr1-Xaa2- and Tyr5-Pro6 peptide bonds. In the case of analogue 7 four separate peaks corresponding to the four possible isomers were apparent at -5 degrees C.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗

PubMed1993

[Crystallographic and molecular structure determination of beta-5-isopropyl-2'-deoxyuridine by x-ray diffraction and comparison with similar 5-alkylated uridine structures].

X-ray crystal structure determination of beta-5-isopropyl-2'-deoxyuridine was performed yielding a structure model at R = 0.061 for 992 data. C(8) terminal methyl carbon atom of the isopropyl moiety lies in the pyrimidine base plane while C(7) and C(9) is displaced from this plane by 0.2 and 1.59 A. The glycosidic torsion angle is 64.4 degrees corresponding to anti conformation. The O5' atom is placed in a gauche-gauche position with respect to O(1') and C(3'). Steric position of the isopropyl moiety suggests that is may considerably hinder development of base stacking in DNA synthesis due to the protruding C(9) atom. Conformation of the molecule was compared for similar structures in the Cambridge Structural Database in order to shed light on the occurrence of such peculiar alignment of bulky 5-substrates.

Alkylation↗

PubMed1989

Fentanyl-midazolam-flumazenil anesthesia for induced abortion.

A new anesthetic method (fentanyl-midazolam-flumazenil) was compared with a previously administered anesthetic regimen (pethidine-diazepam-ketamine) in two groups of 25 women, each of whom underwent termination of pregnancy. No significant difference was found between the two groups in quality of anesthesia. Recovery was assessed by means of the Aldrete score and a visual analog scale. The recovery time was significantly shorter in patients who received the fentanyl-midazolam-flumazenil.

Abortion, Induced↗

PubMed1989

Comparison of the polymorphic modifications of famotidine.

The polymorphic modifications of famotidine are described and characterized by their spectroscopic (infrared, X-ray) and some physico-chemical data. In addition to the standard physico-chemical data (melting point, solubility, bulk density) some further properties influencing its use in pharmaceutical technology are also characterized. The methods used to prepare the morphologically homogeneous modifications are also given.

Calorimetry, Differential Scanning↗