Potassium transport in Langendorff-perfused mouse hearts assessed by 87Rb NMR spectroscopy.

We studied the fluxes of a potassium congener (Rb(+)) in mouse hearts by (87)Rb MRS at 8.4T. The hearts were loaded with Rb(+) by perfusion with Krebs-Henseleit buffer, in which 50% of K(+) was substituted with Rb(+). We initiated Rb(+) efflux by changing the perfusion medium to Rb(+)-free buffer. Spectra were acquired every 1.85 min, and the kinetics of Rb(+) transport were analyzed by means of monoexponential fits. The rate constants of Rb(+) uptake and efflux were 0.0680 +/- 0.0028 and 0.0510 +/- 0.0051 min(-1), respectively (approximately 30% faster than in the rat heart). The ATP-sensitive potassium channel opener, P-1075 (5 microM), and mitochondrial uncoupler, 2,4-dintrophenol (50 microM), activated Rb(+) efflux from mouse hearts by approximately 35%. The mechanisms responsible for the differences in Rb(+) uptake and efflux under baseline conditions and stimulation, in comparison with rat hearts, are discussed. These data provide a background for studies of cardiac potassium transport in transgenic mouse strains.     

Some international differences in treatment and survival in breast cancer

In a recent study, 5-year survival rates for breast cancer patients in Boston (Massachusetts), Glamorgan (Wales), Slovenia (Yugoslavia) and Tokyo (Japan) were 57.3%, 49.5%, 41.9% and 74.9%, respectively. In this report, data are presented on the types of treatment used in the four areas and on the relationship of differences in treatment practices to the differences in survival rates. Generally, surgically treated patients who also had radiotherapy had lower survival rates than patients in the same area who had similar operations without radiotherapy. In each area, the survival rate was higher for patients who had radical mastectomy than for those who had simple mastectomy. The Japenese patients had the highest survival rate within nearly every treatment and extent-treatment category. Thus, the high survival rate of these patients was not explained by the variables considered. Survival differences between Boston, Glamorgan and Slovenia were largely explained by differences in extent of disease and type of treatment. As the nature of the treatment—survival trends was consistent with the interpretation that treatment tended to be selected according to apparent prognosis, the degree to which treatment customs were determinants of the differences in survival rate among the three areas is uncertain.     

Estimation of DNA damage and cytotoxicity of anthracycline analogs in human melanoma cells on early and late passages

Human malignant melanoma is a major problem characterized by both rapid rising incidence and strong chemoresistance. The aim of present experiments was to estimate the effects on DNA of new anthracycline analogs in melanoma cells obtained from various patients, cultured on early (E) and late (L) passages. For determination of cytotoxic effect, MTT assay was used and comet assay was used for the detection of DNA damage. The discrepancy between the intensity of DNA damage processes and IC50 values may indicate that there are some critical loci in the genome, responsible for cell death.     

Diode laser photocoagulation for retinopathy of prematurity--outcomes in one-year observation

PURPOSE: To evaluate structural and functional outcomes in one-year old patients, treated for retinopathy of prematurity (ROP) with transpupillary diode laser photocoagulation. MATERIALS AND METHODS: 58 children (116 eyes) 12 months old, after treatment for ROP with diode laser photocoagulation, were examined. Both, functional outcome (visual acuity--basing on the examination with Teller Acuity Card Procedure), and structural outcome were evaluated. The cycloplegic refraction was examined in all cases. RESULTS: We have found good functional outcome in 81.9%, and good structural outcomes in 96.5% of examined eyes. 64.6% of eyes had hyperopic refractive error, and 31% were myopic. CONCLUSIONS: Diode laser photocoagulation is an effective method of treatment for ROP.     

Bronchial carcinoid--a rare neoplasm metastasis to choroid

PURPOSE: To present a clinical picture and results of treatment in two patients with bronchial carcinoid metastases to choroid. MATERIAL AND METHODS: Two females aged 47 and 56 with bilateral and multiple metastases of bronchial carcinoid were enrolled in this study. Choroidal metastases occurred 6-7 years after primary tumors had been diagnosed. The follow-up period ranged from 2.5 to 5 years. In one patient teleradiotherapy of choroidal metastases was performed, while in a second case plaque therapy with 106 Ru and 125 I and a diode laser therapy were used. RESULTS: After therapy, one patient demonstrated partial regression of two choroidal metastases and total regression of one tumor, while the second one, showed total regression of all intraocular tumors. One patient developed irradiation neuropathy and retinopathy as a result of teleradiotherapy, which were the main cause of decreased visual acuity in her one eye. CONCLUSIONS: Regarding the good prognosis and potentially long survival of patients with bronchial carcinoid, prompt treatment of choroidal metastases is recommended. Applied method of therapy depends on tumor size, its localization and patient's general condition.     

Photodynamic therapy of circumscribed choroidal hemangioma

PURPOSE: To evaluate efficacy of photodynamic therapy (PDT) with verteporfin in treatment of posterior pole symptomatic circumscribed choroidal hemangiomas. MATERIAL AND METHODS: Four patients (3 men and 1 woman), 15-55 years old (mean age: 29 years) with circumscribed choroidal hemangiomas of the posterior pole, were examined. The hemangiomas localization were subfoveal in one patient, extrafoveal in 2 cases, and juxtapapillar in one case. The diagnosis of choroidal hemangioma was established on the base of clinical examination, A and B--scan ultrasound imaging, Doppler ultrasonography, fluorescein and indocyanine angiography results. Tumour thickness before treatment ranged from 2.3-3.6 mm (mean thickness: 2.8 mm). One course of PDT with verteporfin was performed in 3 cases, while in one patient PDT was performed four times. RESULTS: In a follow-up period which range from 3 to 14 months (mean 5.7 months) all cases demonstrated clinical features of lesion regression with a reduction of thickness on ultrasonography and choroidal vasculature on angiograms. Visual acuity was improved in 3 patients (from 1 to 4 lines on Snellen charts), or remained stable in 1 case. CONCLUSIONS: Our preliminary results indicate that PDT with verteporfin is a safe and effective method of treatment for circumscribed choroidal hemangiomas, especially in patients with posterior pole location of the tumour.     

Anticonvulsant and antidepressant activity of the selected terpene GABA derivatives in experimental tests in mice

The present study was designed to investigate the central nervous system activity of terpene GABA (and piracetam) derivatives designated as BF-1, BF-2, BF-3, BF-4, BF-5, BF-6. We assessed their anticonvulsant activity in the two main mouse models of seizures (MES-test, PTZ-test), an antidepressant-like effect in the forced swim test (FST), as well as an influence on spontaneous locomotor activity. Our study demonstrated the strong anticonvulsant activity of (1S,3R,7R)-(-)-3,8,8-trimethyl-4-aza-bicyclo[5.1.0]acetate-5-one hydrochloride (compound BF-2) in the PTZ-test. Activity of BF-2 was equipotent to ethosuximide (380 mg/kg, po) in the PTZ-test, when used at a dose of 100 mg/kg, po. No neurotoxic effects were demonstrated by administration of all tested compounds. Moreover, BF-2, BF-3, BF-6 compounds significantly reduced the immobility time in FST at both doses (by 21-50%), while BF-5 induced a significant anti-immobility effect only when used at a dose of 100 mg/kg (by 39%). The compound BF-6 used at the dose of 30 mg/kg was the most active (50% reduction), and the effect was similar to the result obtained with classical antidepressant--imipramine. The motor stimulatory activity was demonstrated by BF-1 compound at the dose of 100 mg/kg with no effect at a lower (30 mg/kg) dose. On the other hand, the BF-3 at 30 mg/kg significantly decreased spontaneous activity during 30 min observation period, while no alteration in this activity during 6-min observation was detected. At present, it is not possible to indicate which mechanisms of novel, active terpene GABA derivatives are involved in the demonstrated antidepressant-like activity. Although further studies are needed to solve this issue, these data suggest a potential value of the examined terpene GABA derivatives.     

Connexin expression and gap junctional intercellular communication in human squamous cell carcinoma of the head and neck.

OBJECTIVE: Our laboratory is investigating the role that gap junction intercellular channels (composed of proteins called connexins) play in communicating apoptotic signals from therapeutically targeted squamous cell carcinoma of the head and neck (SCCHN) cells to adjacent, untreated, "bystander" cells (bystander effect). The nature of this research underscores the importance of delineating connexin expression patterns in SCCHN, and how this correlates with gap junctional intercellular communication (GJIC) and bystander effects. STUDY DESIGN: The GJIC activity of a diverse panel of SCCHN cell lines, as well as normal oral epithelial (NOE) cell controls was determined in vitro. These data were correlated with connexin expression patterns determined through connexin 43 and connexin 26 immunofluorescence. RESULTS: Cell lines with retained GJIC activity all expressed connexin 43 on the cell membrane. Cell lines that did not communicate microinjected lucifer yellow (lost GJIC activity) showed no connexin expression, either at the cell membrane or in the cytosol. Connexin 26 was not expressed in any of our SCCHN cell lines, whereas both connexin 43 and connexin 26 were expressed in the NOE cell controls. Furthermore, connexin 43 introduction into a GJIC (and connexin) deficient SCCHN cell line conferred no growth inhibitory effect. CONCLUSION: Connexin 43 expression correlates with retained GJIC in SCCHN in vitro. Connexin 26 may have a role as a tumor suppressor in SCCHN. SIGNIFICANCE: The data presented have relevance to our ongoing investigations of gap-junction mediated bystander effects in SCCHN and are being expanded to investigations on actual SCCHN tumor specimens.     

Surgical management of iris melanoma

PURPOSE: To describe the own experiences of surgical treatment of iris melanomas. MATERIAL AND METHODS: 56 patients with iris melanoma were treated between January 1995 and June 2001. Two surgical modalities were used depend on tumor location: partial iridectomy (in 45 cases) or transscleral iridotrabeculectomy (in 11 cases with the iridocorneal angle involvement). Additional ruthenium brachytherapy was performed in 3 cases. RESULTS: There were no any complications during surgery. Filtration bleb occurred in 1 patient during post-operative follow-up. Local recurrence of melanoma successfuly treated with ruthenium plaque appeared in one person. Histologically, the majority were spindle B melanomas (70%), mixed in 27% and epithelioid in 3%. The visual acuity was better or not changed in 90% of cases. CONCLUSIONS: Surgical management of iris melanoma seems to be save and effective treatment.