Electrospray ionization and matrix-assisted laser desorption/ionization mass spectrometric investigation of an imidazolato-bridged Cu-Zn complex that mimics superoxide dismutase.
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Biomedical subjects
Publications and source records attributed to I Szilágyi.
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The solution equilibrium and the binding mode of the species in the five-component system containing two metal ions (copper(II) and zinc(II)) and three ligands (A=diethylenetriamine, B=imidazole, C=tris(2-aminoethyl)amine) were investigated by pH-potentiometric titration, UV-visible spectrophotometry and EPR (electron paramagnetic resonance) spectroscopic titration in aqueous solution in the 2-11 pH range. An imidazolate-bridged heterobinuclear complex (ACuBH(-1)ZnC) was found to evolve above pH=7 and was stable between pH 7 and 11. The existence of the ACuBH(-1)ZnC complex (by determination of its molecular weight) was proved by mass spectrometry (ESI-MS (electrospray ionization mass spectrometry) and MALDI (matrix-assisted laser desorption/ionization) techniques). The electrochemical behaviour and the superoxide dismutase activity of this complex were also tested by cyclic voltammetry and the Riboflavin/NBT (nitro blue tetrazolium) assay, respectively.
Breast cancer is extremely rare in children, and consequently no consensus has been reached on the optimal treatment modalities. The medical history and treatment plan for a 7.5-year old male breast cancer patient is described. Radical mastectomy with sentinel node biopsy was performed in October 2002. As no malignant cells were detected in the sentinel node, and no BRCA1-2 mutations were detected, no further radio- or chemotherapy was performed. A "wait-and-see" policy was decided on. Further treatment will be given if this becomes necessary with the development of metastases.
The appearance of free DNA ends in the chromatin is usually considered an indication of advanced apoptosis. Unexpectedly, the nuclei of non-apoptotic cells derived from mouse thymuses could be specifically labeled by terminal transferase after proteinase K treatment of the fixed, cytocentrifuged samples. Artifactual mechanical or contaminating nucleolytic factors have been ruled out as players in the generation of free DNA ends. The phenomenon was detected in both formaldehyde- and ethanol-fixed specimens, in agarose-embedded fixed cells, and in chromatin spreads. By urea-agarose gel electrophoresis, the average single-strand size of the DNA molecules carrying the free ends was found between 50 and 250 kb. We suggest that ss discontinuities preexisting in the fixed normal cells are unmasked by protease treatment eliciting TUNEL (terminal transferase-mediated nick end-labeling) positivity.
Loop-size chromatin fragmentation frequently observed upon apoptotic cell death is thought to be initiated by ss nicks. Here we show that the agarose-embedded, deproteinized chromatin of normal, non-apoptotic murine and human cells, as well as yeast protoplasts, falls apart to 50-300 kb ss fragments upon heat denaturation, as revealed by urea-TAE field-inversion agarose gel electrophoresis resolving ss and ds fragments alike. These data were in line with S1digestion experiments. The nicks (gaps) observed are best explained either by enzymatic cleavages occurring upon cell lysis instantaneously or by preexisting discontinuities becoming manifest upon heat denaturation. These discontinuities go unnoticed in the usual nondenaturaing circumstances but seem to be inevitably present in any DNA preparation. The loop-size ds DNA fragmentation in apoptosis may be based on these pre-existing or "ready-to-go" (upon cell lysis) ss discontinuities of the normal cellular chromatin.
The thermal behaviour of Selegiline (a chiral, non racemic pharmaceutical used in the therapy of Parkinson disease) was studied by differential scanning calorimetry (DSC) for determining the enantiomeric purity (e.p.) of the bulk substance. It has been found, that (i) the binary phase diagram (melting point phase diagram) of the R/S enantiomer mixtures is characteristic to that of the true racemic compounds; (ii) the melting behaviour of the R/S binary mixtures follows the thermodynamic laws (i.e. the Schröder-Van Laar and the Prigogine-Defay equations); (iii) the e.p. of the highly purified bulk substance can be expressed as "DSC purity" (this latter is obtained from the Van't Hoff equation) and the microcalorimetric method as above gives good reproducibility; (iv) due to the minor impurities (other than the S(-) enantiomer) the obtained e.p. (expressed as DSC purity) can be higher but not lower than the actual e.p. of the investigated substance.
A series of N-(phosphonoacetyl)-dipeptide derivatives was synthesized for pharmacological testing as antihypertensive compounds. Several of these compounds demonstrated a moderate antihypertensive effect in Wistar spontaneous hypertensive rats (SHR) with p.o. dosing. ACE inhibition by the compounds was studied using ACE from rat plasma and lung. Inhibitors containing esterified C-termini are pro-drugs and showed activity only for plasma ACE.
The authors have been performing intrauterine insemination with the washed sperm of the husband since 1986. Previous to the intervention husband and wife went through a very thorough infertility examination according to the principles of the WHO. The cycle of women given intrauterine insemination was monitored. The maximum value of estradiol was measured on the 12th and 13th day of the cycle and the maximum mean value of the follicles on the 13th-14th day. In cases of ovulation the mean value of serum progesterone was found to rise on the 14th-15th day of the cycle. The semen was washed and concentrated, different protein components and bacteria were eliminated and the fraction with good motility was used for insemination. Intrauterine insemination with washed human sperm was carried out with 2 groups of patients. In the series studied the authors induced with intrauterine insemination 24 pregnancies in 100 infertile marriages. Intrauterine insemination was found to be successful if the infertility was caused by the hostility or poor quality of the cervix mucus. The treatment may be successful also in cases with slighter alteration of the spermiogram, whereas no results can be expected from intrauterine insemination with spermiograms displaying more serious alteration.
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Intrauterine insemination with washed semen has been carried out in our department since the beginning of 1986. Couples are examined carefully according to the principles of WHO before entering the program. The cycles of those couples treated by intrauterine insemination were monitored. Oestradiol values showed the highest levels on days 13 and 14, such as the size of folliculi, and serum progesterone level increased on days 14 and 15 ovulatory cycle. Insemination was performed with washed sperm after cleansing from it different albumin components and bacteria; the insemination was carried out in two groups. Good results were achieved in cases where the poor quality or hostility of the cervical mucus was the cause of infertility. The treatment can be successful if the spermiogram does not show severe deviation. No success can be expected in severe deviation of the spermiogram.
Thirty-two cases of malignant Müllerian tumours of the uterus of the mixed mesodermal type were investigated. Histological examinations were performed on tissue obtained during curettage or biopsy and/or surgical removal of the uterus; in 4 cases postmortem examination was also carried out. The biphasic tumours of the uterus were classified into four groups and comprised 44% of alle uterine sarcomas. In 10 of the 28 cases in which uterine curettage or cervical biopsy was carried out, the final diagnosis was clarified when the tumorous uterus was removed. The prognosis was poorer for heterologous than for homologous tumours. In the heterologous group, the prognosis was better for the form with chondrosarcomatous features (2 patients are still alive after more than 5 years) than for the form containing striated muscle tissue (all 5 patients died within 1 year). Attention is drawn to the fact that the adenosarcoma should be considered a separate type; its prognosis was relatively good (2 such patients are still alive after more than 5 years).
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A scanning electron microscopic study of the chondropathy of the patellar articular surfaces following knee injury was made. The early signs of degeneration were evident in the superficial membrane. Here, the fibres running parallel with the surface then turning deep become irregularly arranged, i.e. the amount of matrix embedding the fibres was reduced and the uncovered fibres became fragmented causing degeneration of the superficial membrane. During the progressive pathological process, as a result of the gradual deterioration of the interterritorial substance of the uncovered hyaline cartilage, spaces, fissures and deep pits were formed in the upper, then the lower, articular layers. The degeneration involved also the chondrons. With the disintegration of the chondrons the external and internal cell areolae disappear, the cell nests of chondrocytes are opened and the cells degenerate. Finally, the irregular cellular and fibrous structures and their remnants as well as the elements of connective tissue proliferation initially associated with the degenerative process can be visualized ultrastructurally.
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The effects of a loading dose of pyridoxine (100 mg) given intramuscularly or per os to 24 earlier non-supplemented pregnant women at term was investigated. The in vitro oxygen affinity (P50) and the prolactin level in both maternal and newborn blood was sampled. The blood P50 values were measured by a variant of "mixing method". Blood prolactin levels were determined by RIA. After pyridoxine administration, the maternal P50 values increased moderately and the newborns' cord blood P50 values increased significantly when compared with the control group's (number of cases 12) values. The decrease of blood oxygen affinity was most pronounced in the supplemented groups in newborns' capillary blood at the age of five days. The pyridoxine supplementation had no effect on the maternal and the newborns' cord blood prolactin level or on the daily amount of breast milk. Pyridoxine supplementation of the mother at labour may influence favourably the oxygen transport function of the newborn's blood and it may be especially advantageous in early postnatal adaptation disturbances of newborns.