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Biomedical subjects

Z Horvath

Publications and source records attributed to Z Horvath.

13 recordsLinked to original sources
PubMed2006

Resveratrol, an ingredient of wine, acts synergistically with Ara-C and tiazofurin in HL-60 human promyelocytic leukemia cells.

Resveratrol (RV), a naturally occurring stilbene derivative, is a potent free radical scavenger causing a number of biochemical and antineoplastic effects. It was shown to induce differentiation and apoptosis in leukemia cells and was also identified as an inhibitor of ribonucleotide reductase (RR), a key enzyme of DNA synthesis. In this study, we report about the biochemical effects of RV in HL-60 human promyelocytic leukemia cells. RV effectively inhibited in situ RR activity. Furthermore, incubation of HL-60 cells with RV significantly decreased intracellular dCTP, dTTP, dATP and dGTP concentrations. In growth inhibition and clonogenic assays, RV acted synergistically with both Ara-C and tiazofurin in HL-60 cells. We conclude that RV could become a viable candidate as one compound in the combination chemotherapy of leukemia and therefore deserves further in vitro and in vivo testing.

Antimetabolites, Antineoplastic↗
PubMed2006

Antitumor effects of 3,3',4,4',5,5'-hexahydroxystilbene in HL-60 human promyelocytic leukemia cells.

Resveratrol (3,4',5-trihydroxystilbene, RV) exerts remarkable cytostatic and cytotoxic effects against a multitude of human cancer cell lines. Since the introduction of additional hydroxyl groups was supposed to increase the biological activity of RV, we have synthesized a number of polyhydroxylated stilbene analogues as potential antitumor agents. In this study, the activity of 3,3',4,4',5,5'-hexahydroxystilbene (M8) was investigated in HL-60 human promyelocytic leukemia cells. Employing a growth inhibition assay, incubation with M8 and RV resulted in IC50 values of 6.25 and 12 microM, respectively. Using a specific Hoechst/propidium iodide double staining method, we found that M8 was able to induce apoptosis in concentrations significantly lower than those of RV. In addition, M8 arrested cells in the S phase and totally depleted cells in the G2-M phase of the cell cycle (143% and 0% of control after treatment with 12.5 microM M8, respectively). We therefore believe that this promising agent deserves further preclinical and in vivo testing.

Antineoplastic Agents↗
PubMed2004

Cytotoxic and apoptotic effects of novel heterodinucleoside phosphates consisting of 5-fluorodeoxyuridine and Ara-C in human cancer cell lines.

In search for possible alternatives in the treatment of human malignancies we investigated several new heterodinucleoside phosphates consisting of 5-Fluorodeoxyuridine (5-FdUrd) and Arabinofuranosylcytosine (Ara-C). We show that all dimers tested inhibited the number of colonies of CCL228, CCL227, 5-FU resistant CCL227 and HT-29 human colon tumor cells with IC50 values ranging from 0.65 to 1 nM. Dimer # 2 inhibited the number of sensitive and Ara-C resistant H9 human lymphoma cells with IC50 values ranging from 200 to 230 nM. Since no significant difference in the cytotoxicity of the dimers could be observed between sensitive and resistant cells, these compounds might be used in the treatment of 5-FU and Ara-C resistant tumors.

Antimetabolites, Antineoplastic↗
PubMed2004

Amidox, an inhibitor of ribonucleotide reductase, potentiates the action of Ara-C in HL-60 human promyelocytic leukemia cells.

Amidox (3,4-dihydroxybenzamidoxime), a new polyhydroxy-substituted benzoic acid derivative, is a potent inhibitor of the enzyme ribonucleotide reductase (RR), which catalyses the de novo synthesis of DNA. RR is considered to be an excellent target for cancer chemotherapy. In the present study we investigated the antineoplastic effects of Amidox alone and in combination with Arabinofuranosylcytosine (Ara-C) in HL-60 human promyelocytic leukemia cells. In growth inhibition experiments Amidox yielded an IC50 of 30 microM, colony formation was inhibited at an IC50 of 20 microM as determined by a soft agar assay. Exposure of the cells to 75 and 100 microM Amidox for 24 hours was shown to significantly decrease intracellular dCTP, dGTP and dATP pools, whereas dTTP concentration increased, as determined by HPLC. The combination of Amidox with Ara-C yielded more than additive cytotoxic effects both in growth inhibition assays and in soft agar assays. We could show that--after preincubating the cells with 75 and 100 microM Amidox and subsequent exposure to Ara-C--intracellular Ara-CTP levels increased by 576% and 1143%, respectively. In conclusion, Amidox might offer an additional option for the treatment of leukemia and thus be further investigated in vitro and in vivo.

Agar↗
PubMed1996

Optimization of Flow Injection On-Line Microcolumn Preconcentration of Ultratrace Elements in Environmental Samples prior to Their Spectrochemical Determination

The preconcentration of some elements such as Cd, Co, Ni, and V(IV) was modeled in the presence of complexing agents such as citrate and oxalate at high Ca, Mg, and sulfate concentrations on iminodiacetic acid/ethyl cellulose (IDAEC), a chelating cellulose. The effect of the species present in the solution was studied after construction of the species distribution curves using critical, estimated, and measured stability constants. The stability constants of the IDAEC chelates were determined potentiometrically. The constants were calculated or estimated using computer programs. The diagrams calculated in homogeneous media were used for optimization of the flow injection on-line preconcentration for analysis of ultratrace metals in the highly mineralized water "Hunyadi."

Journal Article↗
PubMed1995

Spike-and-wave epilepsy in rats: sex differences and inheritance of physiological traits.

Spontaneously occurring spike-and-wave patterns were examined in seven to eight-month-old rats of the inbred Fischer 344 and Brown Norway strains and their F1 and F2 hybrids. Neocortical activity and movement were monitored for 12 night h. Spike-and-wave episodes were identified by a three-layer back-propagation neural network. The incidence, average duration and total duration of spike-and-wave episodes were significantly higher in F1 males and F2 hybrids than in the parental strains. Male rats of the Brown Norway strain had significantly more and longer episodes than females, whereas no sex differences were present in Fischer rats. The average intraepisodic frequency of spike-and-wave patterns was significantly lower in Fischer rats than in the other groups and significantly higher in males than females. Tremor (myoclonic movements) associated with spike-and-wave episodes was absent or of very small amplitude in Fischer rats but frequent and of large amplitude in Brown Norway rats and their F1 and F2 descendants. Most of the interstrain differences were limited to male rats. Spike-and-wave episodes recurred at predictable short-term (10-30 s) and long-term (15-30 min) periods. The long-term oscillation corresponded to a similar fluctuation of motor activity. The maximum probability of spike-and-wave patterns occurred at a relatively narrow range of delta power (0-3.1 Hz) of the background EEG activity. Systemic administration of the adrenergic alpha-2 agonist, clonidine, increased the incidence of spike-and-wave episodes several-fold. The total duration of spike-and-wave episodes in the clonidine sessions (15 min) and night sessions (12 h test) correlated significantly. We suggest that several genes interact with maturational, environmental and endocrine factors, resulting in sex differences, and produce the variety of EEG and behavioral findings encountered. In addition, we submit that the clonidine test may be useful in genetic investigations of human absence epilepsies. The findings of this work demonstrate that genetic manipulation of rodents is a promising method for producing analogous models for the various forms of human absence epilepsies.

Animals↗
PubMed1991

Distributed changes in rat brain DNA synthesis with long-term habituation and potentiation of the perforant path-granule cell synapse.

The involvement of brain deoxyribonucleic acid (DNA) synthesis in adaptive neural events was studied in the adult rat during long-term habituation (LTH) or potentiation (LTP) of the perforant path-granule cell synapse. Male Long-Evans rats were given 50 muCi [3H]thymidine intraventricularly under urethane anesthesia. Soon thereafter, field excitatory postsynaptic potential (EPSP) slope and population spike were monitored from the right dentate gyrus before and at various times (5, 10, 15, 60 min) following the delivery to the ipsilateral perforant bundle of a low frequency (LFS: 1.0 Hz, 160 s) or a high-frequency train (HFS: 400 Hz, 200 ms), repeated once after 5 min. Unstimulated implanted rats served as controls. DNA synthesis was evaluated by the incorporation of the radioactive precursor into DNA of several brain areas at the end of a 1 h incorporation period. In CA1, LTH and LTP increased DNA synthesis by 30% on the stimulated side. In the entorhinal cortex, LTH but not LTP increased DNA synthesis (by 30%) on the stimulated side. Conversely, in the frontal cortex, LTP but not LTH increased DNA synthesis (by 100%) on both sides. Long-lasting changes in synaptic efficacy covaried non-linearly with DNA synthesis in mono- and polysynaptically stimulated hippocampal regions, and in functionally associated neocortical areas. The co-variations of population spike amplitude were positive for LTH and negative for LTP in the dentate gyrus and frontal cortex of both sides, and in CA3/CA1 of the stimulated side, indicating higher DNA synthesis at lower values of LTH and LTP, and viceversa. Further, regional cross-correlation analyses revealed a high degree of synchronization among brain sites, following low- or high-frequency train pulses, indicating that (i) extra-target sites participate on the stimulated and on the contralateral side, and (ii) small distributed changes take place across the sampled neural networks. A modulatory role of information flow on brain DNA synthesis is inferred to take place in a diffuse, distributed manner.

Animals↗
PubMed1987

Mood disorder and multiple sclerosis.

A systematic psychiatric evaluation was performed on 100 consecutive patients attending a multiple sclerosis clinic. Forty-two percent of the patients had lifetime history of depression, and 13% fulfilled criteria for manic-depressive illness. Only 28% of the patients had no psychiatric diagnosis. The relationship of psychiatric disorder to neurologic dysfunction and other aspects of multiple sclerosis are presented. Clinical and theoretical implications of these findings are discussed.

Adult↗
PubMedDate not supplied

Personal and family history of affective illness in patients with multiple sclerosis.

There is a high prevalence of affective illness, both depression and bipolar disorder, in patients with multiple sclerosis. In this study, the family history method was used to assess the prevalence of affective illness in first-degree relatives of patients with multiple sclerosis. There was not an excess of affective illness in the relatives suggesting that affective disorder associated with multiple sclerosis does not have a familial pattern similar to primary affective disorder. Clinical and theoretical implications of these findings are discussed.

Adult↗
PubMedDate not supplied

[MRI guided stereotactic thalamotomy for the treatment of the neurogenic pain].

INTRODUCTION: Medial thalamotomy is one of the first stereotactic operations to have been used for neurogenic pain, has a low complication rate and no risk of the development of iatrogenic neurogenic pain. It represents selective local relief for all types of pain, without causing somatosensorial deficit. PATIENTS AND METHODS: We did 39 posteromedial thalamotomies in patients with persistent intractable pain due to various disorders. The pain was assessed pre- and postoperatively on the VAS (Visual Analogic Scale). RESULTS: Half of the patients operated on had relief of pain after thalamotomy. In 84% (n = 39) of our cases this relief occurred on the second day, in 70% (n = 35) after three months, in 63% (n = 27) after six months, in 64% (n = 25) after nine months, in 62% (n = 23) of the patients after 12 months, and in 62% (n = 22) after 24 months. Three patients had temporary complications and one a permanent complication, but this did not make him an invalid. CONCLUSION: Posteromedial stereotactic thalamotomy under MR guidance can provide safe, effective treatment for persistent, intractable pain.

Adult↗