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Biomedical subjects

A Popescu

Publications and source records attributed to A Popescu.

At least 19 recordsLinked to original sources

[Rupture of the flexor tendons on an anterior plate for distal radial fracture: four cases and a review of the literature].

We report four cases of flexor tendon ruptures which occurred after distal radial fracture and reviewed the 25 other cases reported in the literature since 1932. Analysis of these 29 cases disclosed the causes of these ruptures. A deformed callus after distal radial fracture or presence of an anterior osteosynthesis plate can under certain conditions lead to secondary flexor tendon tears. It was also found that tears of the flexor pollicis longus rupture predominate, followed by injury to the flexor digitorum profundis and superficialis of the index finger. Other tendons have only been involved in only a few cases. In order to avoid this complication, we propose systematic removal of anterior plates or secondary replacement if the reduction is not totally anatomic. Surgeons should recall the importance of anatomic reduction of distal radial fractures.

Aged↗

The dynamic activation of colicin Ia channels in planar bilayer lipid membrane.

Dynamic activation of ion channels formed by colicin Ia incorporated into a planar bilayer lipid membrane (BLM) was investigated by the voltage clamp technique using different step voltage stimuli. We have demonstrated a critical resting interval, Deltat(c), between two identical successive voltage pulses. If the second pulse is applied within Deltat(c), it produces a predictable current response. On the contrary, if the second pulse is applied after Deltat(c), the current response cannot be reliably predicted. Computer simulations based on an idealized mathematical model, developed in this paper, qualitatively reproduce the system's dynamic responses to stimulus trains. The behavior of the ion channels, when the resting period exceeds Deltat(c), may be interpreted as a transient gain or loss or resetting of memory, as revealed by a specific sequence of electrical pulses used for stimulation.

Animals↗

Carbonic anhydrase inhibitors: inhibition of isozymes I, II and IV by sulfamide and sulfamic acid derivatives.

Sulfamide and sulfamic acid are the simplest compounds containing the SO2NH2 moiety, responsible for binding to the Zn(II) ion within carbonic anhydrase (CA, EC 4.2.1.1) active site, and thus acting as inhibitors of the many CA isozymes presently known. Here we describe two novel classes of CA inhibitors obtained by derivatizations of the lead molecules mentioned above. The new compounds, possessing the general formula RSO2NH-SO2X (X = OH, NH2), were obtained by reaction of sulfamide or sulfamic acid with alkyl/arylsulfonyl halides or arylsulfonyl isocyanates. A smaller series of derivatives has been obtained by reaction of aromatic aldehydes with sulfamide, leading to Schiff bases of the type ArCH = NSO2NH2. All the new compounds act as strong inhibitors of isozymes I, II and IV of carbonic anhydrase. Their mechanism of CA inhibition is also discussed based on electronic spectroscopic measurements on adducts with the Co(II)-substituted enzyme. These experiments led to the conclusion that the new inhibitors are directly coordinated (in a monodentate manner) to the metal ion within the enzyme active site, similarly to the classical inhibitors, the aromatic/heterocyclic sulfonamides.

Animals↗

Carbonic anhydrase inhibitors: synthesis of Schiff bases of hydroxybenzaldehydes with aromatic sulfonamides and their reactions with arylsulfonyl isocyanates.

Reaction of o- or p-hydroxybenzaldehydes with sulfanilamide, homosulfanilamide and p-(2-aminoethyl)- benzene-sulfonamide afforded several new Schiff bases which were subsequently derivatized at the phenolic hydroxy moiety by reaction with arylsulfonylisocyanates. The new arylsulfonylcarbamates obtained in this way possessed interesting inhibitory properties against three carbonic anhydrase (CA) isozymes, hCA I, hCA II and bCA IV (h = human, b = bovine isozyme). All these new derivatives, the simple Schiff bases and the arylsulfonylcarbamates obtained as outlined above, were more inhibitory against all isozymes as compared to the corresponding parent sulfonamide from which they were obtained. Generally, the p-hydroxybenzaldehyde derivatives were more active than the corresponding ortho isomers. An interesting behavior was evidenced for some of the ortho-substituted arylsulfonylcarbamato-sulfonamides, which showed higher affinities for the isozyme hCA I, as compared to hCA II and bCA IV (generally hCA I is 10-1000 less sensitive to "normal" sulfonamide inhibitors, such as acetazolamide, methazolamide or dorzolamide, as compared to hCA II). This make the new derivatives attractive leads for designing isozyme I-specific inhibitors.

Animals↗

Multinuclear magnetic resonance studies of Escherichia coli adenylate kinase in free and bound forms. Resonance assignment, secondary structure and ligand binding.

The crystal structure of Escherichia coli adenylate kinase (AKe) revealed three main components: a CORE domain, composed of a five-stranded parallel beta-sheet surrounded by alpha-helices, and two peripheral domains involved in covering the ATP in the active site (LID) and binding of the AMP (NMPbind). We initiated a long-term NMR study aiming to characterize the solution structure, binding mechanism and internal dynamics of the various domains. Using single (15N) and double-labeled (13C and 15N) samples and double- and triple-resonance NMR experiments we assigned 97% of the 1H, 13C and 15N backbone resonances, and proton and 13Cbeta resonances for more than 40% of the side chains in the free protein. Analysis of a 15N-labeled enzyme in complex with the bi-substrate analogue [P1,P5-bis(5'-adenosine)-pentaphosphate] (Ap5A) resulted in the assignment of 90% of the backbone 1H and 15N resonances and 42% of the side chain resonances. Based on short-range NOEs and 1H and 13C secondary chemical shifts, we identified the elements of secondary structure and the topology of the beta-strands in the unliganded form. The alpha-helices and the beta-strands of the parallel beta-sheet in solution have the same limits (+/- 1 residue) as those observed in the crystal. The first helix (alpha1) appears to have a frayed N-terminal side. Significant differences relative to the crystal were noticed in the LID domain, which in solution exhibits four antiparallel beta-strands. The secondary structure of the nucleoside-bound form, as deduced from intramolecular NOEs and the 1Halpha chemical shifts, is similar to that of the free enzyme. The largest chemical shift differences allowed us to map the regions of protein-ligand contacts. 1H/2H exchange experiments performed on free and Ap5A-bound enzymes showed a general decrease of the structural flexibility in the complex which is accompanied by a local increased flexibility on the N-side of the parallel beta-sheet.

Adenylate Kinase↗

Wedge factor dependence with depth, field size, and nominal distance--a general computational rule.

We have investigated the dependence of the wedge factors with field size, depth, nominal, and extended distances for 4, 6, 18, and 24 MV photon beams. Analysis of the experimental data suggests a general linear dependence of the wedge factors with field size and depth. The study shows that changes in wedge factors are insignificant (< or = +/-1.0%) with respect to measurements at nominal SSD, SAD, or extended SSD. This independence of the wedge factors on source-to-surface distance was studied for different photon energies (4-24 MV) and for different attenuating wedges (external and internal wedges). For clinical applications, an algorithm is presented to calculate the wedge factor dependence with field size and depth. The new algorithm has been successfully implemented to replace wedge look-up tables for dose and MU calculations in PRISM 1.2 treatment planning system used in our department.

Algorithms↗

Carbonic anhydrase inhibitors. Schiff bases of some aromatic sulfonamides and their metal complexes: towards more selective inhibitors of carbonic anhydrase isozyme IV.

Reaction of three aromatic sulfonamides possessing a primary amino group, i.e., sulfanilamide, homosulfanilamide and p-aminoethyl-benzenesulfonamide with heterocyclic and aromatic aldehydes afforded a series of Schiff bases. Metal complexes of some of these Schiff bases with divalent transition ions such as Zn(II), Cu(II), Co(II) and Ni(II) have also been obtained. The new compounds were assayed as inhibitors of three isozymes of carbonic anhydrase (CA). Several of the new compounds showed a modest selectivity for the membrane-bound (bovine) isozyme CA IV (bCA IV) as compared to the cytosolic human isozymes hCA I and II, in contrast to classical inhibitors which generally possess a 17-33 times lower affinity for bCA IV. This greater selectivity toward bCA IV is due mainly to a slightly decreased potency against hCA II relative to classical inhibitors. However, metal complexes of these Schiff bases possessed an increased affinity for hCA II, being less inhibitory against bCA IV. The first type of compounds reported here (i.e., the Schiff bases of aromatic sulfonamides with heterocyclic aldehydes) might thus lead to the development of low molecular weight isozyme specific CA IV inhibitors. The difference in affinity for the three isozymes of the inhibitors reported by us here is tentatively explained on the basis of recent X-ray crystallographic studies of these isozymes and their adducts with substrates/inhibitors.

Aldehydes↗

[The vitreoretinal complications of cataract surgery].

The paper reports a retrospective study performed between January 1996 and January 1999 which comprised 423 patients who underwent eye cataract surgery. Vitreoretinal complications (retinal detachment, cystoid macular edema, choroidal detachment, endophthalmitis, luxation of the lens into the vitreous body) were related to age, sex, other general and local diseases and surgical complications, like disruption of the posterior capsule. The study presents also vitreoretinal complications after Nd:YAG laser posterior capsulotomy. The outcomes of the study show that 18 cases (4.25%) had retinal detachment, 11 (2.60%) had cystoid macular edema, 2 cases had endophthalmitis, while choroidal detachment and luxation of the lens into the vitreous body were reported each in 1 case. Retinal detachment following Neodymium:YAG laser capsulotomy (performed in 109 cases) was found in 2 cases. All of those vitreoretinal complications were reported with a higher incidence in patients with vascular diseases (diabetes mellitus, arterial hypertension, angiosclerosis) and also in patients who had axial lengths of 25 mm or greater.

Aged↗

Mutation spectrum and phenylalanine hydroxylase RFLP/VNTR background in 44 Romanian phenylketonuric alleles.

The mutation spectrum and polymorphic haplotype background in 22 Romanian families have been analysed in this study using the restriction digestion of phenylalanine hydroxylase (PAH) regions specifically amplified or the DGGE/direct sequencing methods. Eleven PAH mutations specifically associated with six mutant haplotypes were detected. In spite of the relative heterogeneity of the molecular defects in the PAH gene, three mutations covered almost 70% of all alleles: R408W, 47.72%, 21/44; K363fsdelG 13.63%, 6/44; and P225T 6.81%, 3/44. Among these, R408W, the most frequent mutation in our population, represented 50% of all the phenylketonuric (PKU) chromosomes. Splice mutation IVS12nt1g-->a affected two PAH alleles (4.54%); the remaining seven mutations were rare, each having an effect on just one chromosome (1/44), resulting in a relative frequency of 2.27%. A high frequency was observed in our PKU samples for the relatively uncommon mutations, K363fsdelG and P225T mutation, suggesting a possible founder effect at origin. Within the investigated panel, these mutations, both very rare among other Caucasians were exclusively linked to haplotype 5.8 and 1.7, respectively. These results provide a basis for the development of a routine molecular analysis of Romanian PKU families.

Adult↗

[The use of viscoelastic compounds in cataract surgery].

The viscoelastic substances are very useful generally in cataract surgery, but absolutely useful in phacoemulsification. In present is used for viscoelastic compounds two terms that assemble the rheologic and physics-chemical properties: is said about the viscoelastic substance that is cohesive and dispersive (respective cohesivity or dispersivity property). Thus both types of viscoelastic substances--cohesive and dispersive--is used, sequentially, in one system. This double technique provides a fluid, heterogeneous work environment, which differ from the other techniques that use only one viscoelastic substance and provide a fluid, homogeneous work environment.

Cataract Extraction↗

[Vascular risk factors in glaucoma].

The study realised in the Eye Clinic of the Central Military Hospital during February 1995-November 1997 analyses the impact of the vascular risk factors on the evolution of the primary glaucoma. The group consists in 533 patients which primary open angle glaucoma, from which 90.6% patients with primary open angle glaucoma and 9.3% with normal tension glaucoma. The assessment of the patients in order to identify the vascular risk factors it was performed on the basis of anamnestic questionnaire, following: degenerative vasculopathies, spastic vasculopathies, arterial hypotension and coronary insufficiency. 70.5% of the patients presented minimum one vascular risk factor. In the case of the patients with primary open angle glaucoma, we found a high frequency of the degenerative vasculopathies. In the patients with normal tension glaucoma the most frequent factor were: arterial hypotension and spastic vasculopathies. The coronary insufficiency had equal distribution in the primary open angle glaucoma and normal tension glaucoma. The parameters of the disease were affected faster in the patients with vascular risk factors. The outcomes of the study allow to estimate that the screening of the vascular risk factors has a distinct importance in the evolution and accurate treatment of glaucoma.

Aged↗

[Cataract and the exfoliative syndrome].

Exfoliation syndrome is more frequently in the older age and represents a risk factor for cataract surgery. This paper presents the results of a clinical trial made on 436 patients with troubles of transparency of the lens who were investigate in our clinic during January 1995-January 1997, and in whom, clinic and paraclinic exams have not revealed any associated ocular disease. In 14% of these patients who presented troubles of transparency of the lens were found uni- or bilateral exfoliation. The authors present the treatment applied both in patients in clinical follow-up (50% of patients with exfoliation syndrome develop secondary glaucoma) and patients who underwent surgical treatment. The patients with exfoliation syndrome and cataract have had a high risk to develop intra- and postoperative complications. The surgical treatment suggested by authors is extracapsular cataract extraction, either or without lens implantation and peripheral iridectomy which represents a compulsory step.

Aged↗

An approach to establishing a health information market.

The Tempus CME project "Regional Network for Healthcare Management" was aiming to perform a feasibility study for a communication network dedicated to the healthcare field. The needs assessment survey as well as the debates during the working sessions and during the conference on how communication can support a better healthcare delivery, substantiated the approach for achieving the Romanian health information market. The proposed communication network can be considered as a national information infrastructure offering good links between health, education, research and industry and a unique frame for information providers and users, for the estate and private companies. The network should also provide support and guidance for the development of new educational fields as applied informatics in healthcare.

Computer Communication Networks↗

Resolution of enantiomers of uridine analogs, potential antiviral agents.

Racemic mixtures of 5-substituted carbocyclic analogs of uracil nucleosides, 2"- and 3"-furyl, 2"- and 3"-thienyl and 2"-selenienyl, potentially anti-viral agents, were resolved using amylose tris(3,5-dimethylphenyl)carbamate as the stationary phase. The mobile phase was n-hexane with ethanol or 2-propanol. Effects of some structural features on the extent of discrimination between the enantiomers were examined through the selectivity and resolution factors as well as the elution order. The structural features were as follows; the type and position of the hetero-atom O, S or Se, in the cyclopentadienyl substituent 5 of the uracil and hydroxymethyl vs. acetoxymethyl groups on the cyclopentene moiety of the uridine analogs. It appeared that effects of the structural features on the separation were solvent dependent, with some very unusual solvent effects. For example, average retention, which did not follow the polarity of the mobile phase modifiers, was much higher when ethanol was used compared to 2-propanol. Also, the elution order of the two enantiomers of several pairs was reversed when ethanol was changed to 2-propanol. In general, ethanol affected higher selectivity and resolution of all the enantiomeric pairs.

Antiviral Agents↗

Three-dimensional structure of the immunophilin-like domain of FKBP59 in solution.

FKBP59 is a protein usually associated with heat-shock protein hsp90 and steroid receptors. The N-terminal domain of the rabbit liver protein (149 amino acids) has a sequence homology with FKBP12, binds FK506 immunosuppressor, and has a peptidyl-prolyl cis-trans isomerase activity. The three-dimensional structure of this domain (FKBP59-I) was determined using homo- and heteronuclear multidimensional NMR spectroscopy, distance geometry, and molecular dynamics methods. Structure calculations used 1290 interproton distance restraints derived from nuclear Overhauser enhancement measurements, 29 dihedral phi angle restraints, and 92 hydrogen bond restraints. For the final 22 structures, the root mean square distance from the mean atomic coordinates, calculated for well-defined secondary structure fragments, is 0.47 +/- 0.05 and 1.26 +/- 0.15 A for backbone heavy atoms (N, C alpha, C') and for all non-hydrogen atoms, respectively. The global fold contains a twisted six-stranded antiparallel beta-sheet and a short alpha-helix packed on the hydrophobic side of the sheet. The 20 N-terminal and 12 C-terminal amino acids of the domain are disordered. The main-chain structure of FKBP59-I is globally similar to the NMR-derived and X-ray structures of unbound FKBP12. An unusual hydrogen bond interaction between the indole amino proton of Trp 89 and the aromatic cycle of Phe 129 was observed. This gives a large upfield shift (-4.8 ppm) and a significant exchange protection factor. The implications of the present structure determination on the ligand binding of FKBP59 are discussed.

Amino Acid Sequence↗

The Gram stain after more than a century.

The Gram stain, the most important stain in microbiology, was described more than a century ago. Only within the past decade, however, has an understanding of its mechanism emerged. It now seems clear that the cell wall of Gram-positive microorganisms is responsible for retention of a crystal violet:iodine complex. In Gram-negative cells, the staining procedures damage the cell surface resulting in loss of dye complexes. Gram-positive microorganisms require a relatively thick cell wall, irrespective of composition, to retain the dye. Therefore, Gram-stainability is a function of the cell wall and is not related to chemistry of cell constituents. This review provides a chronology of the Gram stain and discusses its recently discovered mechanism.

Gentian Violet↗