Alterations of cerebrospinal fluid 5-hydroxyindoleacetic acid,and total blood serotonin content during clozapine treatment

Cerebrospinal fluid 5-hydroxyindoleacetic acid level, and total blood serotonin content was measured in groups of manic and schizophrenic patients before and after 2, 4, 6, 10, 20, and 30 days of clozapine treatment. CSF 5-HIAA values were elevated after 2 and 4 days and returned to baseline levels after 6 days or more. Blood serotonin content, in contrast, increased gradually and remained high even after 30 days. Neither CSF 5-HIAA nor blood 5-HT correlated with age, drug dose, or clinical effectiveness, but some relationship between these and the sedative component of the clozapine action was observed.     

Survivin splice variants regulate the balance between proliferation and cell death

Survivin is an inhibitor of apoptosis protein that also plays critical roles in regulating the cell cycle and mitosis. Its prominent expression in essentially all human malignancies, and low or absent expression in most normal tissues, suggests that it would be an ideal target for cancer-directed therapy. Impeding development of safe and effective survivin antagonists for clinical use is a lack of understanding of the molecular mechanisms by which survivin differentially affects apoptosis and cell division, in normal and malignant cells. We show that the diverse functional roles of survivin can be explained, in part, by its heterodimerization with survivin splice variants in tumor cells. Survivin and survivin-DeltaEx3 interact within the mitochondria where they may inhibit mitochondrial-dependent apoptosis. If the expression of all survivin forms is eliminated by siRNA transfections, cells undergo both apoptosis and defective cell division. Overall, we provide new insights suggesting that targeting specific survivin isoforms, rather than survivin alone, may selectively and effectively destroy tumor cells. These findings are likely to have a significant impact in the design of biologic agents for clinical therapy.     

Potential of endogenous estrogen receptor beta to influence the selective ER modulator ERbeta complex

The ratio of estrogen receptor beta (ERbeta) to ERalpha can alter the estrogen-like properties of tamoxifen. Transient transfection of ERbeta cDNA into cells can decrease the estrogen-like properties of the ERalpha:tamoxifen complex, whereas an increase in the amount of ERbeta is associated with tamoxifen-resistant breast cancer. We have addressed each of these hypotheses by examining well characterized laboratory models. We determined whether changes in endogenous ERbeta are responsible for the estrogen-like or antiestrogenic properties of tamoxifen or raloxifene in MDA-MB-231 cells transfected with cDNAs for ERalpha or mutants D351G, D351Y. We found that the amount of ERbeta mRNA in separate, stable transfectants of mutant ERalpha cDNA was always < 2% of ERalpha. Since at least a 50:50 mixture of ERalpha:ERbeta is needed to silence the tamoxifen:ERalpha complex, we conclude that insufficient ERbeta mRNA is available for selective ER modulation in stable transfectants of D351G and D351Y ERalpha. Similarly, to test the hypothesis that ERbeta is up-regulated and plays an important role during the development of tamoxifen-stimulated tumor growth, we quantitatively analyzed ERbeta and ERalpha mRNA in tamoxifen-na?ve (MCF-7:E2, ECC1:E2) and tamoxifen-stimulated tumors (MCF-7:TAM, EnCa 101:TAM). We found that ERbeta mRNA levels were not significantly elevated in tamoxifen-stimulated tumors and the ERalpha mRNA remained over 99% out of all ER species for all the tumors tested. The same results were also obtained when mRNA levels of ERbeta and ERalpha in a series of tamoxifen-na?ve and tamoxifen-resistant breast cancer was analyzed. We conclude that endogenous ERbeta may not play a dominant role in the modulation of the tamoxifen ERalpha complex, or in the development of tamoxifen-stimulated resistant tumor growth.     

Treatment of children's and adolescent's knee injuries

INTRODUCTION: Authors made 162 knee arthroscopic operations due to hemarthrosis of the knee, acute knee blocking or acute developed instability on patients under 18 years after knee injury during a 12 years period. The retrospective analysis of patient reports shows, that in 61.7% of the cases they found chondral- or osteochondral fracture in the knee. MATERIAL AND METHODS: On three dimensional routine X-ray pictures they were performed after the injury, in 85% of the cases fractures were not seen. Fortunately the most part of the hyalin surface injuries was smaller than 0.5 cm or were situated on less weight-bearing area only hemarthrosis evacuation and removing of loose body were done. If the osteochondral fractures was bigger than 0.5 cm or was broken from the weight-bearing surface, they were fixed by KFI or Herbert-screws. When refixation of osteochondral fracture was not possible technically or in cases of chondral fractures, primary mosaic chondroplasty was used. The correct diagnosis and the early reconstruction of injured hyalin surface in childhood and teenagers is essential regarding to the function of the knee.     

Catheter ablation for supraventricular tachycardia in children and congenital heart diseases

INTRODUCTION: Recently catheter ablation has been accepted as standard therapy for symptomatic supraventricular tachycardia in children. Nature of childhood and the variability of congenital heart diseases and congenital heart surgery distinguishes pediatric catheter ablation from the adult practice. OBJECTIVES: The aim of the present study was to summarize a single-center experience of the first 30 consecutive patients regarding the electrophysiological studies and catheter ablations, moreover to report on the national adoption of these interventions for pediatric patients in Hungary. METHODS: Between April 1996 and September 2004 catheter ablation was offered for 30 children as treatment of their supraventricular tachycardia because of failure of pharmacological therapy or parents preference. RESULTS: The mean age of the patients was 13.7 years (2.3-18.0 years) and the mean weight was 52.0 kg (12.0-81 kg). Electrophysiology study revealed 33 arrhythmogenic substrates in 30 patients, 30 of those 33 were congenital while 3 were acquired. Catheter ablation was attempted in 27 patients with acute success in 24 cases (89%). Recurrence was observed in 2 patients and the redo ablation was effective in both, although a second recurrence occurred later in one of them. There were no major complications, but two minor ones (pseudoaneurysm of arteria femoralis, transient ventricular ectopy) occurred. CONCLUSIONS: Catheter ablation is safe and effective in children with congenital heart disease. Our results are comparable with the international data.     

The environmental estrogen bisphenol a inhibits estradiol-induced hippocampal synaptogenesis

Bisphenol A (BPA) is an estrogenic chemical that is widely used in the manufacture of plastics and epoxy resins. Because BPA leaches out of plastic food and drink containers, as well as the BPA-containing plastics used in dental prostheses and sealants, considerable potential exists for human exposure to this compound. In this article we show that treatment of ovariectomized rats with BPA dose-dependently inhibits the estrogen-induced formation of dendritic spine synapses on pyramidal neurons in the CA1 area of the hippocampus. Significant inhibitory effects of BPA were observed at a dose of only 40 microg/kg, below the current U.S. Environmental Protection Agency reference daily limit for human exposure. Because synaptic remodeling has been postulated to contribute to the rapid effects of estrogen on hippocampus-dependent memory, these data suggest that environmental BPA exposure may interfere with the development and expression of normal sex differences in cognitive function, via inhibition of estrogen-dependent hippocampal synapse formation. It may also exacerbate the impairment of hippocampal function observed during normal aging, as endogenous estrogen production declines.