Search PubMed⌕ Search

Biomedical subjects

M Mezei

Publications and source records attributed to M Mezei.

At least 19 recordsLinked to original sources
PubMed2000

Genetic subtypes of HIV type 1 in Hungary.

We examined the diversity of HIV-1 subtypes in 11 adults from Hungary, using the heteroduplex mobility assay (HMA) and DNA sequencing. HMA results showed that HIV-1 gp120 sequences from 10 patients were of subtype B, whereas 1 patient, infected in Africa, carried a subtype C strain. DNA sequencing confirmed the HMA results and revealed a high intrasubtype diversity in the C2V3 region of env in different clade B isolates, which suggests multiple introduction of subtype B to Hungary. This study shows that subtype B is the predominant HIV-1 clade in Hungary.

Acquired Immunodeficiency Syndrome↗
PubMed2000

Calculating the local solvent chemical potential in crystal hydrates.

Determining solvation patterns in biological systems is crucial in investigating the functional role water may play in structural stabilization and molecular recognition. Determining whether a particular position would be occupied by a solvent molecule requires the local thermodynamics to be known. In this work we introduce a simple and inexpensive approach based on grand canonical molecular simulations to determine the occupancy factors of the cavities. The method is applied to the test case of the sodium salt of hyaluronic acid. The results agree very well with experimental results and demonstrate the success of the method.

Color↗
PubMed2000

Transdermal formulations of deprenyl: guinea pig and pig models.

The efficacy of many drugs relies on their presence at the site of action over a period of time. The retardation or programmed release capability of the conventional dosage forms like oral and parenteral are limited and toxic and undesired side-effects may occur after their applications. These problems may be solved using transdermal delivery systems. Transdermal systems are aimed for local, or systemic action. In the letter case controlling the rate of delivery or modulating the distribution in the organism. The selection of an adequate biological method of evaluating a new transdermal formulation is a critical point of the development. The in vitro methods can help in the characterization of the different formulas, but without an in vivo disposition study they cannot give relevant information about the expectable therapeutic behavior. We adapted and improved an in vivo test system for the evaluation of new transdermal particulate systems (patches) and liposomes containing deprenyl selegiline as active ingredient. The in vivo evaluation system consists of two steps: 1. Full biodisposition study on guinea pig, using isotope labeled selegiline. 2. Biodisposition studies on domestic pigs including dose, area, surface dependence and comparative bioavailability with traditional dosage forms and application moods. Specific examples of these studies and experimental technology are presented.

Administration, Cutaneous↗
PubMed1999

Motor system abnormalities in heterozygous relatives of a D90A homozygous CuZn-SOD ALS patient of finnish extraction.

Presently, 64 mutations in the gene encoding the enzyme CuZn-superoxide dismutase have been found in a small fraction of amyotrophic lateral sclerosis patients worldwide. All but one of these mutations show autosomal dominant inheritance. In Scandinavia, the D90A mutation is inherited as an autosomal recessive trait and patients have an easily recognizable characteristic phenotype with little variation among patients, even amongst different families. Importantly, all D90A heterozygous relatives of Scandinavian D90A homozygous patients have been reported as clinically unaffected. We have investigated a Canadian family of Finnish extraction in which the D90A homozygous proband developed ALS with the characteristic phenotype. Remarkably, two D90A heterozygous relatives show slight symptoms and signs of motor system involvement, suggesting that the final phenotype of an individual with a CuZn-superoxide dismutase mutation is shaped by the combination of the particular CuZn-SOD mutation, other polymorphic modifying genes elsewhere in the genome, stochastics and possible environmental factors.

Aged↗
PubMed1999

Influence of lamotrigine on progression of early Huntington disease: a randomized clinical trial.

OBJECTIVE: To assess the efficacy of lamotrigine, a novel antiepileptic drug that inhibits glutamate release, to retard disease progression in Huntington disease (HD). BACKGROUND: Excitatory amino acids may cause selective neuronal death in HD, and lamotrigine may inhibit glutamate release in vivo. METHODS: A double-blinded, placebo-controlled study was conducted of 64 patients with motor signs of less than 5 years' duration who were randomly assigned to either placebo or lamotrigine and assessed at 0 (baseline), 12, 24, and 30 months. The primary response variable was total functional capacity (TFC) score. Secondary response variables included the quantified neurological examination and a set of cognitive and motor tests. Repeated fluorodeoxyglucose measurements of regional cerebral metabolism using PET also were included. RESULTS: Fifty-five patients (28 on lamotrigine, 27 on placebo) completed the study. Neither the primary response variable nor any of the secondary response variables differed significantly between the treatment groups. Both the lamotrigine and the placebo group deteriorated significantly on the TFC, in the lamotrigine group by 1.89 and the placebo group by 2.11 points. No effect of CAG size on the rate of deterioration could be detected. CONCLUSIONS: There was no clear evidence that lamotrigine retarded the progression of early Huntington disease over a period of 30 months. However, more patients on lamotrigine reported symptomatic improvement (53.6 versus 14.8%; p = 0.006), and a trend toward decreased chorea was evident in the treated group (p = 0.08). The study also identified various indices of disease progression, including motor tests and PET studies, that were sensitive to deterioration over time.

Adult↗
PubMed1999

[Headspace solid phase micro-extraction method optimization for residual solvent analysis].

A systematic headspace SPME method optimization is described for the residual solvent analysis using a polidimethyl-siloxane/divinylbenzene (PDMS/DVB) fiber. The first step was the chromatographic system optimization in which a narrow bore capillary column with a thick film (1 micron) of stationary phase, low starting column temperature (30 degrees C) and a narrow bore injector liner (2 mm I.D.) were used. It was found that for the investigated components a desorption temperature of minimum 150 degrees C should be used. The second step was the extraction optimization. The optimum equilibration time for all components was 30 min. It was found that the sample headspace volume has an important effect on method sensitivity and precision. At low headspace volumes (less than 1/3 of vial volume) sensitivity improves but at the same time precision worsen. The optimum headspace volume was found to be 4.6 ml. The total organic content does also have an important effect on method sensitivity and precision. At low organic content sensitivity increases but precision drops significantly. Over 1% organic content in the sample the system becomes unstable due to stationary phase swelling by the organic components. The optimum range for total organic content was found to be between 0.1% and 1%. The added NaCl quantity does increase the extraction yield. The optimum salt quantity to be added was 2 g NaCl in 5 ml sample. The last step was the desorption optimization. The influence of injector temperature and injection depth on desorption were investigated and it was found that it does not have an important effect on desorption yield. The optimum desorption temperature was 220 degrees C and the optimum injection depth was 2 cm into the injector. Among the investigated fibers the best detection limits and chromatographic behavior were given by the PDMS/DVB fiber. The measured detection limits were between 10 and 100 pg/ml and the RSD data were between 1-3%.

Chromatography↗
PubMed1998

Computer simulation studies of the fully solvated wild-type and mutated GnRH in extended and beta-turn conformations.

The conformational preference of the gonadotropin-releasing hormone (GnRH) and its Lys-8 mutant, studied earlier with a continuum model, was revisited using an explicit solvent model and thermodynamic integration to calculate the solvents contribution to the conformation-dependence of its free energy. In addition, the Proximity Criterion was used to further analyze the effects of conformational changes.

Computer Simulation↗
PubMed1998

Topical anaesthesia of intact skin: liposome-encapsulated tetracaine vs EMLA.

In this randomized, double-blind study, we have compared the ability of 5% liposome-encapsulated tetracaine (amethocaine) (LET) vs 5% eutectic mixture of local anaesthetics (EMLA) to produce local anaesthesia of intact skin in 40 healthy volunteers. Volunteers had both preparations applied to their forearms under an occlusive dressing for 1 h. Superficial anaesthesia was measured by a total of nine 1-mm pinpricks on each arm. Deeper anaesthesia was assessed by single insertion of a sterile 22-gauge needle to a depth of 3 mm and pain was reported on a visual analogue scale (VAS). If the volunteer perceived greater than four of the 1-mm pinpricks, the 3-mm insertion was not performed. Results showed that the number of pinpricks perceived was significantly less (P < 0.01) for LET (median 1.0; range 0-9) vs EMLA (1.5; 0-9). In volunteers who had deeper anaesthesia assessed, there was no significant difference (P = 0.065) in VAS scores for LET (mean 1.5 (SD 1.4); n = 34) vs EMLA (2.4 (2.1); n = 28). Overall anaesthetic effect, as ranked by all of the subjects, was significantly better for LET compared with EMLA (P = 0.024). We have demonstrated that when applied in equal volumes, 5% LET produced better superficial local anaesthesia than EMLA.

Administration, Cutaneous↗
PubMed1998

Chameleon sequences in the PDB.

The Brookhaven Protein Data Bank has been searched for sequences that can be found both in helix and sheet conformation. The longest such sequences consist of seven residues.

Amino Acid Sequence↗
PubMed1997

Evidence for a long-lasting single administration contraceptive vaccine in wild grey seals.

A single-administration birth control vaccine based on liposome delivery of porcine zona pellucida antigens reduced pup production in grey seals (Halichoerus grypus) by about 90%. Anti-porcine zona pellucida titers of individual seals with two or more recaptures were variable but without a diminishing trend during the 5 year post-immunization period. Seals that produced at least one or more pups during the 2-5 year post-immunization period when the vaccine is fully effective, had an average anti-porcine zona pellucida titer of 5% of the reference serum. In contrast, the subset of seals that did not reproduce but were recaptured during the breeding season had an average titer of 31% of the reference serum. As measured by antibody titers and pup production, there were no differences in efficacy of the vaccine in 14-, 20- and 21-year-old female grey seals.

Age Factors↗
PubMed1997

Temporal trends in antibody production in captive grey, harp and hooded seals to a single administration immunocontraceptive vaccine.

The temporal production of antibody to a single-administration immunocontraceptive vaccine, known to be immunocontraceptive in free-ranging female grey seals (Halichoerus grypus), was studied in captive grey seals, harp seals (Phoca groenlandica) and hooded seals (Cystophora cristata). The vaccine is based on liposome delivery of porcine zona pellucida antigens. When measured by antigen capture, the response of hooded and harp seals to the vaccine was similar to the response of grey seals. Determination of antibody production by ELISA with protein A, ELISA with rabbit anti-seal immunoglobulin sera and SDS-PAGE after affinity chromatography confirmed the similarity in response to the vaccine by grey and harp seals, but suggested lower titers in hooded seals. The vaccine produced titers in captive, juvenile grey and harp seals known to be immunocontraceptive in wild, adult grey seals.

Animals↗
PubMed1997

The sensitivity of conformational free energies of the alanine dipeptide to atomic site charges.

Different atomic point charge sets are obtained for the alpha R and C7,eq conformations of the alanine dipeptide by fitting the charges of each conformation to the respective ab initio electrostatic potential surfaces both individually and simultaneously, in both the united atom and the all-atom representations. Using these charge sets, the sensitivity of the relative conformational aqueous free energies to the atomic site charges is investigated. For this particular system, we find that the solute-water contributions to the conformational free energy differences have a rather weak dependence on site charges; the calculated intramolecular contributions, however, show a rather strong dependence on the atomic site charges. It is suggested that the calculated results for the alanine dipeptide using a single, simultaneously fit set of charges for both conformations are in better agreement with experiments than the calculations carried out with charges determined individually for each conformation.

Binding Sites↗
PubMed1997

Comparative topical anaesthesia of EMLA and liposome-encapsulated tetracaine.

BACKGROUND: The eutectic mixture of local anaesthetics (EMLA) provides effective topical anaesthesia after a minimum of 60 to 90 min application. Since liposome-encapsulated tetracaine (LET) can provide rapid dermal penetration, the goal of this study was to compare the local anaesthetic effects of EMLA and LET in human volunteers after 60 min application. METHODS: After obtaining institutional approval and informed consent, healthy volunteers were recruited in a double blind, crossover, randomized trial. The study creams (0.5 ml EMLA and 0.5 ml LET 5%) were applied randomly to opposite arms for 60 min. The discomfort of i.v. catheterization was assessed using a visual analogue pain score (VAS). Cutaneous side effects of the creams were recorded. RESULTS: Sixty-one subjects were studied. Twenty-one were excluded because of technical difficulties. Forty subjects completed the study and were included in the data analysis. The mean ( +/- SD) VAS was lower for LET than for EMLA (10.9 +/- 9.0 mm vs 22.7 +/- 17.1 mm, P < 0.001). Erythema secondary to vasodilatation occurred more frequent in the LET group than in the EMLA group (33 vs 3, P < 0.001). One subject with a history of atopy developed a rash at the LET application site. CONCLUSION: Liposome-encapsulated tetracaine can provide a more effective topical anaesthesia than EMLA for intravenous catheterization after 60 min application. Clinical evaluations are necessary to determine the efficacy and safety of LET in providing topical anaesthesia for various invasive percutaneous procedures in other patient populations.

Administration, Topical↗
PubMed1996

Grand canonical ensemble Monte Carlo simulation of the dCpG/proflavine crystal hydrate.

The grand canonical ensemble Monte Carlo molecular simulation method is used to investigate hydration patterns in the crystal hydrate structure of the dCpG/proflavine intercalated complex. The objective of this study is to show by example that the recently advocated grand canonical ensemble simulation is a computationally efficient method for determining the positions of the hydrating water molecules in protein and nucleic acid structures. A detailed molecular simulation convergence analysis and an analogous comparison of the theoretical results with experiments clearly show that the grand ensemble simulations can be far more advantageous than the comparable canonical ensemble simulations.

Binding Sites↗
PubMed1996

Superficial siderosis--a cause of audiovestibular failure.

Bilateral vestibular end organ failure in adult life is a rare condition with some specific known causes, such as relapsing polychondritis, autoimmune inner ear disease, Lues venerium, and an acute effect of gentamicin. This case report draws attention to a rare condition that is potentially recognizable early in its development. The patient has superficial siderosis, which is iron deposits over the cerebrum, resulting in progressive neurologic failure involving all of the systems. Early in its course before other symptoms appear, there is development of progressive hearing loss and vestibular failure. This case report and literature review are given, including a potential for attempts at therapy if the disorder is recognized early.

Brain Diseases↗
PubMed1995

A role for amplified protein kinase C activity in the pathogenesis of amyotrophic lateral sclerosis.

Amyotrophic lateral sclerosis (ALS) is a human neurodegenerative disorder of unknown origin that is characterized by progressive degeneration of corticospinal tracts and anterior horn cells in the brainstem and spinal cord. Previous studies have indicated that motoneuron degeneration associated with ALS may be triggered by mechanisms leading to increased intracellular Ca2+. In the present report, Ca(2+)-activated phospholipid-dependent protein kinase C (PKC) was evaluated in cervical spinal cords from ALS patients and control subjects. In patients who died with ALS, PKC histone H1 phosphotransferase activity was significantly increased by 330% in cytosolic- and 118% in particulate-derived extracts compared with controls. This increase in PKC phosphotransferase activity appeared to be partially due to an increase in the amount of PKC protein present in ALS spinal cord tissue. PKC histone H1 phosphotransferase activities of cytosolic- and particulate-derived extracts from motor and visual cortex of ALS patients and controls were not statistically different, nor were there differences in PKC histone H1 phosphotransferase activity in platelets and leukocytes. The specific nature of PKC alterations in affected regions of the CNS supports a role for PKC in the events leading to motoneuron death in sporadic ALS.

Aged↗
PubMed1995

Pharmacokinetics of inhaled liposome-encapsulated fentanyl.

BACKGROUND: Pulmonary administration of fentanyl solution can provide satisfactory but brief postoperative pain relief. Liposomes are microscopic phospholipid vesicles that can entrap drug molecules. Liposomal delivery of fentanyl has the potential to control the uptake of fentanyl by the lungs and thus provide sustained drug release. To demonstrate that inhalation of a mixture of free and liposome-encapsulated fentanyl can provide a rapid increase and sustained plasma fentanyl concentrations (CfenS), this study determined the pharmacokinetic profiles after the inhalation of free and liposome-encapsulated fentanyl in healthy volunteers. METHODS: After obtaining institutional approval and informed consent, ten healthy volunteers (five men, five women) were studied. Each subject received 200 micrograms intravenous fentanyl and inhaled 2,000 micrograms of free (50%) and liposome-encapsulated fentanyl (50%) on separate occasions. Frequent venous blood samples were collected, and CfenS were determined by radioimmunoassay. The pharmacokinetics and absorption characteristics of the inhaled mixture of free and liposome-encapsulated fentanyl were determined using moment analysis and least-squares numeric deconvolution. RESULTS: The mean (+/- SD) volume of distribution at steady-state and clearance of fentanyl after the intravenous administration were comparable to previous studies: 435 +/- 1821 and 0.584 +/- 0.209 l.min-1, respectively. The mean (+/- SD) peak Cfen was significantly greater for the intravenous administration compared to the aerosol mixture of free and liposome-encapsulated fentanyl (4.67 +/- 1.87 vs. 1.15 +/- 0.36 ng.ml-1). However, CfenS at 8 and 24 h after aerosol administration were greater compared to intravenous (0.25 +/- 0.14 and 0.12 +/- 0.16 ng.ml-1 for aerosol versus 0.16 +/- 0.10 and 0.05 +/- 0.06 ng.ml-1 for intravenous). The peak absorption rate, time to peak absorption, and bioavailability after inhalation were 7.02 (+/- 2.34) micrograms.min, -1(16) (+/- 8.0) min, and 0.12 (+/- 0.11), respectively. CONCLUSIONS: The data suggest that this analgesic method offers a simple and noninvasive route of administration with a rapid increase of Cfen and a prolonged therapeutic fentanyl concentration. Future studies are required to determine the optimal liposome composition that would produce a sustained stable Cfen within analgesic therapeutic concentrations.

Adult↗