bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effectiveness of Eye Drops Protective against Ultraviolet Radiation
Authors: Daxer Albert , Blumthaler Mario , Schreder Josef , Ettl Armin 
Published: April 2003

<b>Background:</b> To test the effectiveness of commercially available ultraviolet (UV)-protective eye drops (8-hydroxy-1-methylchinolinium methylsulphate) which are recommended for protection against both solar and artificial UV radiation. <b>Methods:</b> The spectral transmission in the wavelength range from 250 to 500 nm was investigated in 1-nm steps using a high-resolution double monochromator with holographic gratings of 2,400 lines/mm and a 1,000-watt halogen lamp as light source. The transmission spectrum was measured for different values of the layer thickness. <b>Results:</b> The transmission of a liquid layer of about 10 µm, which corresponds to the thickness of the human tear film, shows a cut-off at 290 nm with a transmission of about 25–50% at shorter wavelengths. For wavelengths longer than 290 nm the transmission is higher than 90%. The threshold time ratio for keratitis formation with and without eye drops is above 0.93 considering solar radiation on the earth’s surface and above 0.65 considering radiation from arc-welding, respectively. <b>Discussion:</b> The transmission spectrum of the eye drops under realistic conditions does not show a protective effect against solar UV radiation. However, there exists reduction of UVC radiation in the spectral range typical of artificial UV sources such as arc-welding. We cannot recommend the application of these eye drops as an UV-protective aid against eye damage by solar UV radiation.
Effect of Retinoic Acid on Proliferation and Polyamine Metabolism in Cultured Bovine Retinal Pigment Epithelial Cells
Authors: Yasunari Takaharu , Yanagihara Nobuyo , Komatsu Toshiro , Moriwaki Mitsuyasu , Shiraki Kunihiko , Miki Tokuhiko , Yano Yoshihisa , Otani Shuzo 
Published: April 2003

Reports regarding the effect of all-trans-retinoic acid (RA) on the cell growth of retinal pigment epithelial cells (RPE) have been contradictory. The aims of this study are to clarify the in vitro effect of RA on RPE cells and to examine polyamine metabolism after RA stimulation. A 4-day incubation of fetal-calf-serum (FCS)-stimulated RPE cells with 10 or 25 µM RA significantly increased both cell number and [<sup>3</sup>H]thymidine incorporation. RPE cells grown over an extended period for 8 days also increased in number and reached full confluency. However, if the incubation was further extended to 12 days, no further increase in cell number was detected. RA treatment of FCS-stimulated RPE cells shifted the peak of ornithine decarboxylase (ODC) activity from 16 to 4 h. S-adenosylmethionine decarboxylase (SAMDC) activity and spermidine/spermine N<sup>1</sup>-acetyltransferase (SAT) activity of RA-treated RPE cells were significantly greater until 8 and 16 h after incubation, respectively. The putrescine content was significantly increased in RA-treated RPE cells up until 24 h, while spermidine, spermine and N<sup>1</sup>-acetylspermidine contents were significantly increased until 16 h. Our findings suggest that RA treatment increases the intracellular polyamine concentration of RPE cells via activation of ODC, SAMDC and SAT and that this results in the promotion of RPE cell growth until the cells reach full confluency.
Pharmacokinetics of Azithromycinin Rabbit Lacrimal Glands and Conjunctiv a
Authors: Karcioglu ZeynelA. , Ahmed WaelS. , Raines Dale , El-Yazigi Adnan 
Published: April 2003

<i>Purpose and Background:</i> To measure azithromycin levels in rabbit lacrimal and Harder glands, conjunctiva and plasma after a single oral dose of 20 mg/kg. Drug levels in lacrimal gland tissue are significant in trachoma because the gland may be involved in the disease process and it is the source of tears by which the drug is carried to the external eye. <i>Methods:</i> Lacrimal and Harder glands, conjunctiva and plasma were collected from New Zealand white female rabbits at 24, 48, 72, 96 and 144 h following a single oral dose of azithromycin (20 mg/kg). Azithromycin levels in tissue and plasma were measured using high-performance liquid chromatography (HPLC) electrochemical detection. <i>Results:</i> Azithromycin levels peaked within the first 24 h in all tissues and plasma assayed. The highest concentration was in the lacrimal gland (6.2 µg/g, SD ± 0.8), followed by Harder gland (4.4 µg/g, SD ± 0.8), conjunctiva (0.9 µg/g, SD ± 0.5) and plasma (0.06 µg/g, SD ± 0.03). These concentrations reached their lowest measured levels at 120 and 144 h. <i>Conclusion:</i> Azithromycin levels measured throughout the 144 h after dosing were consistently above the minimum inhibitory range (MIC) for Chlamydia trachomatis (0.03–0.25 µg/ml) in the lacrimal glands, while the conjunctiva maintained a concentration above the MIC for 96 h and stayed within MIC levels for 144 h.
Alpha-Tocopherol Derivatives in an Experimental Model of Filtering Surgery
Authors: Pinilla I. , Larrosa J.M. , Polo V. , Honrubia F.M. 
Published: April 2003

<i>Purpose:</i> To evaluate the efficiency and reliability of α-tocopherol in an experimental model of glaucoma filtering surgery. <i>Methods:</i> Thirty pigmented rabbits were randomly divided into three study groups. Twenty-four hours before surgery, the animals were injected subconjunctivally with 0.5 ml of solution that depended on the group of treatment: group I (n = 10), 0.75% ethanol in balanced saline solution (BSS); group II (n = 10), 100 mg α-tocopherol acetate (ATA) in 0.75% ethanol in BSS; group III (n = 10), 100 mg α-tocopherol acid succinate (ATS) in 0.75% ethanol in BSS. The animals were followed during 30 days (intraocular pressure, IOP; filtering surgery; inflammatory reaction). <i>Results:</i> IOPs were significantly lower in the treatment groups (ATA and ATS) than in the control group from days 7 and 10, respectively, till the end of the study. On day 7, the mean IOP in the ATA group was 15.8 versus 22.1 mm Hg in the control group. On day 10, the mean IOP in the ATS group was 15 versus 22.78 mm Hg in the control group. Filtering blebs showed statistically significant differences between the control and treated groups from day 5 to day 16. <i>Conclusions:</i> α-Tocopherol (ATA and ATS) showed better IOP control and bleb survival in this experimental model of filtering surgery.
Cytokine Production and Antibodies against Heat Shock Protein 60 in Cardiomyopathies of Different Origins
Authors: Mándi Yvette , Hőgye Márta , Talha Elyas M. , Skolák Eszter , Csanády Miklós 
Published: April 2003

<i>Objective:</i> There is growing evidence that proinflammatory cytokines play an important role in a variety of cardiac pathophysiological conditions. The purpose of this study was to determine the circulating tumour necrosis factor (TNF) and interleukin-6 (IL-6) levels in patients with dilated cardiomyopathy (DCM) (n = 40) or ischaemic heart disease (IHD) (n = 38) in comparison with the corresponding data from patients with hypertrophic cardiomyopathy (HCM) (n = 10) or valvular aorta stenosis (AS) (n = 10) and from healthy blood donors (n = 20). <i>Methods:</i> To investigate the possible sources of cytokines, the in vitro cytokine-inducing capacity of the patients’ peripheral blood leucocytes was also measured. The TNF and IL-6 expression levels in the myocardium were investigated from biopsy specimens. The study of the immunological background of the cardiomyopathies was supplemented with screening of anti-heat shock protein 60 (Hsp60) antibodies in the sera of the patients. <i>Results:</i> Elevated levels of circulating TNF (25–150 U/ml) and IL-6 (50–500 pg/ml) were found in 85% of the patients in the DCM and IHD groups, whereas only the IL-6 level was elevated (125–500 pg/ml) in the HCM patients. The in vitro TNF-α production was higher than in the normal controls only in the DCM group. The ventricular tissue of the DCM patients expressed TNF-α and IL-6. In vitro experiments were performed to examine the production of TNF and IL-6 by cultured rat cardiac myocytes (H9C2) under hypoxic conditions. Even a short hypoxic treatment resulted in cytokine production between 4 and 72 h following reoxygenization. Considerable amounts of anti-Hsp60 antibodies were found in 80% of the IHD patients and in 65% of the DCM patients. The in vitro cytokine production of leucocytes and the frequency of anti-Hsp60 positivity in patients with HCM or AS was not significantly different from those in the normal blood donors. <i>Conclusions:</i> These results demonstrate that TNF-α and IL-6 are of pathophysiological importance in some but not all types of cardiomyopathies, and the sources of cytokine production may differ. The mechanism of the development of primary DCM is still unknown; the high in vitro production of proinflammatory cytokines in the leucocytes of patients with DCM, the presence of TNF and IL-6 in their cardiac tissue and the high prevalence of anti-Hsp60 antibodies in their sera suggest a strong immunological background in the pathophysiology of the disease.
Laser Microdissection and Microsatellite Analyses of Breast Cancer Reveal a High Degree of Tumor Heterogeneity
Authors: Wild Peter , Knuechel Ruth , Dietmaier Wolfgang , Hofstaedter Ferdinand , Hartmann Arndt 
Published: April 2003

Carcinomas with productive fibrosis are the most common forms of breast cancer. Analysis of tumor-specific genomic alterations can be compromised by the presence of normal cells, demanding microdissection of small tumor areas to detect loss of heterozygosity (LOH) and microsatellite instability (MSI). The aim of this study was to evaluate the importance of precise laser microdissection for microsatellite analyses and investigation of tumor heterogeneity in breast cancer. 39 primary breast tumor samples were analyzed for MSI and LOH by PCR followed by polyacrylamide gel electrophoresis and silver staining using 15 microsatellite markers. Different tumor areas were processed separately in 30 patients. Both intraductal and invasive breast cancer regions were investigated in 11 patients. The following results were obtained: (1) accurate microdissection revealed MSI in 3 or more of the investigated markers (≧20%) in 33% of the patients, a higher frequency than reported previously; (2) laser microdissection was 43% more sensitive in detection of LOH compared to manual microdissection due to a reduction of contamination by normal cells, and (3) 29 of 30 investigated tumors showed heterogeneity of genetic alterations in different tumor regions. Laser-based microdissection is a valuable tool in genetic analysis of desmoplastic tumors and allows an accurate determination of genetic alterations in histologically different tumor regions.
Permanent Low-Activity <sup>125</sup>I Seed Placement for the Treatment of Pediatric Brain Tumors: Preliminary Experience
Authors: Rostomily Robert C. , Halligan John , Geyer Russ , Stelzer Keith , Lindsley Karen , Berger Mitchel S. 
Published: April 2003

Although external beam radiation therapy is effective in the treatment of many pediatric brain neoplasms its use in this patient population has been associated with the development of significant cognitive and endocrine dysfunction and is severely limited as an option in previously irradiated patients. Therefore, we have adopted a strategy for management of residual microscopic disease by implantation of low-activity <sup>125</sup>I seeds in the tumor bed at the time of surgery. Six patients aged 2–14 years with recurrent tumors including two supratentorial primitive neuroectodermal tumors (n = 2), one medulloblastoma, one malignant ependymoma (n = 1), glioblastoma (n = 1) and one pleomorphic xanthoastrocytoma were implanted at the time of reoperation. A total of 11–126 seeds were implanted resulting in total doses of 16–21.8 Gy (after theoretical infinite time) at a depth of 5 mm from the implanted resection bed. Five patients had prior external beam radiation while the other patient (2 years old at initial diagnosis) progressed after surgery and chemotherapy. Two patients had lasting local tumor control. One patient is alive at 390 weeks of follow-up and another who died of distant failure at 366 weeks had no recurrence on MRI at 333 weeks’ follow-up. Only 2 patients had first local failures. These results suggest that the use of permanent low-activity <sup>125</sup>I seeds as an adjunct to surgery can provide good local tumor control and is a suitable treatment option for pediatric patients.
Modulatory Effect of Protein Kinase C Activator on Contractility of Rat Vas deferens
Authors: Huang Yu , Pai Raymond K. , Lau C.W. , Chan F.L. , Chen Z.Y. , Yao X.Q. 
Published: April 2003

The modulatory effect of the protein kinase C activator was examined on contraction of rat isolated vas deferens induced by constrictive agonists, noradrenaline (NA), ATP, BaCl<sub>2</sub> and high K<sup>+</sup>. Phorbol 12,13-diacetate (PDA, 1 µmol/l) induced a transient extracellular Ca<sup>2+</sup>-dependent contraction while the inactive analogue, 4α-phorbol (1 µmol/l) had no effect. PDA significantly enhanced the peak amplitude of the contractile response to NA (0.1–10 µmol/l), ATP (100 µmol/l), Ba<sup>2+</sup> (3 mmol/l) or high K<sup>+</sup> (30 mmol/l). Staurosporine at 30 nmol/l reduced the enhancing effect of PDA on the agonist-induced contraction. NA (10 µmol/l) produced a phasic contraction followed by a sustained contraction, while ATP induced monophasic contraction. Pretreatment with nifedipine (10 nmol/l) had no effect on the phasic contraction induced by NA, but it significantly reduced ATP- or high K<sup>+</sup>-induced contraction. Staurosporine (30 nmol/l) alone attenuated the peak contractile response induced by NA or ATP but not by Ba<sup>2+</sup>. NA produced a transient contraction in Ca<sup>2+</sup>-free Krebs solution, and PDA (1 µmol/l) markedly enhanced this effect. These novel data indicate that activation of a protein kinase C-dependent mechanism not only affects contraction mediated by Ca<sup>2+</sup> influx through voltage-sensitive Ca<sup>2+</sup> channels, but also promotes intracellular Ca<sup>2+</sup> release or intracellular Ca<sup>2+</sup>-mediated contractile mechanism in rat vas deferens.
Gastric Emptying in Diabetic Gastroparetic Dogs: Effects of SK-951,a Novel Prokinetic Agent
Authors: Takeda Motohiro , Mizutani Yuka , Yamano Masaya , Tsukamoto Katsura , Suzuki Tsunemasa 
Published: April 2003

We examined whether delayed gastric emptying could be produced by diabetes in dogs. Diabetes was produced by a single injection of streptozotocin (30 mg/kg i.v.), and diabetic hyperglycemia was observed from 2 to 15 months after injection. The plasma acetaminophen concentration, which is an indirect indicator of the gastric emptying rate, was delayed in 2 of 5 diabetic dogs from 15 months after the induction of diabetes. The effects of SK-951, a benzofuran derivative, on delayed gastric emptying were also examined in diabetic gastroparetic dogs in comparison with those of cisapride. SK-951 (1 mg/kg i.v.) significantly enhanced delayed gastric emptying in diabetic dogs, but cisapride (1 mg/kg i.v.) had no effect. In addition, SK-951 increased the plasma glucose levels in a manner correlated with its effect on gastric emptying. The present study suggested that SK-951 may be useful in the treatment of diabetic gastroparesis.
Effects of a Novel Hepatoprotective Drug, ZNC-2381, on Fas-Induced Hepatocellular Caspase-3 Activity and Apoptosis in Mice
Authors: Segawa Yoshihide , Tsuzuike Naoki , Itokazu Yoshihiko , Omata Takeshi , Inoue Naonori , Nagasawa Masaaki , Nishioka Hiroyasu , Nakano Yoshihisa , Kobayashi Tadashi , Kanda Takashi 
Published: April 2003

We examined the effects of ZNC-2381 (1-(4-aminophenyl)methyl-3-(3-nitrophenyl)-1,3-dihydroimidazo[4,5-b] pyridine-2-one), a new oral hepatoprotective agent, on hepatocellular caspase-3 activity and apoptosis induced by anti-mouse Fas antibody (anti-Fas ab) in mice. Oral ZNC-2381, administered at doses of 10, 30 and 100 mg/kg 1 h before inducing hepatic injury with anti-Fas ab, dose-dependently inhibited the increase in serum alanine aminotransferase (s-ALT) activity 8 h after injection of anti-Fas ab. Increases in DNA fragmentation (nucleosome assay) and caspase-3 activity in the liver 2 h after injection of anti-Fas ab were also inhibited by ZNC-2381 in a dose-dependent manner. As shown by histopathological examination, ZNC-2381 dose-dependently inhibited the appearance of TUNEL-positive apoptotic cells in the liver. Moreover, in studies in vitro, ZNC-2381 (1– 100 µmol/l) concentration-dependently inhibited increases in DNA fragmentation and caspase-3 activity caused by anti-Fas ab in isolated mouse hepatocytes. N- Acetyl-Asp-Glu-Val-Asp aldehyde (Ac-DEVD-cho), a caspase-3-specific inhibitor, inhibited hepatocellular apoptosis caused by anti-Fas ab both in vivo and in vitro, as well as the increase in s-ALT activity in vivo. These results demonstrate that orally administered ZNC-2381 inhibits hepatocellular apoptosis induced by anti-Fas ab and presents the progression of hepatic injury. We propose that the mechanism of action of ZNC-2381 may involve blockade of the signal transduction pathway (caspase-3) of apoptosis mediated by anti-Fas ab.
Pharmacological Properties of Excitation-Contraction Mechanisms in Isolated Mouse Left Atria
Authors: Nishimaru Kazuhide , Makuta Ryuji , Tanaka Yoshio , Tanaka Hikaru , Shigenobu Koki 
Published: April 2003

Effects of 4-aminopyridine (4-AP), nicardipine and ryanodine on the action potential and contractile force were examined in isolated mouse left atria. The mouse left atria had an action potential with an extremely short duration and two phases of repolarization; action potential duration at 50% repolarization was 6.7 ± 0.4 ms (n = 15). The action potential duration, as well as contractile force, was increased by 4-AP (at 100 µmol/l and 1 mmol/l). Nicardipine (3 µmol/l), which is known to greatly reduce the contractile force in atria of most other experimental animal species, had no significant effect on the action potential and decreased contractile force by only 40% in mouse atria. Ryanodine (10 nmol/l) decreased the contractile force by 90% of basal value. At 100 nmol/l, ryanodine slightly affected the action potential configuration, which could be explained by indirect effects through inhibition of Ca<sup>2+</sup> release from the sarcoplasmic reticulum. The extremely short action potential duration and the highly sarcoplasmic reticulum-dependent contraction of the mouse atria appear to underlie its unique response to agonists.
Effect of SR59230A on Atypical β-Adrenoceptor Mediating Relaxation in the Guinea Pig Gastric Fundus
Authors: Horinouchi Takahiro , Yamamoto Yoshihisa , Koike Katsuo 
Published: April 2003

The purpose of the present study was to clarify whether atypical β-adrenoceptors which presented in the guinea pig gastric fundus are β<sub>3</sub>-adrenoceptors or putative β<sub>4</sub>-adrenoceptors. In the presence of both the selective β<sub>1</sub>-adrenoceptor antagonist atenolol (10<sup>–4</sup> mol/l) and the selective β<sub>2</sub>-adrenoceptor antagonist butoxamine (10<sup>–4</sup> mol/l), the selective β<sub>3</sub>-adrenoceptor antagonist SR59230A caused a concentration-dependent rightward shift of the concentration-response curve to catecholamines (isoprenaline, noradrenaline and adrenaline) and β<sub>3</sub>-adrenoceptor agonists (BRL37344 and CGP12177A) in the guinea pig gastric fundus. Schild plot analyses of SR59230A against these agonists gave pA<sub>2</sub> values of 7.35 ± 0.03 (isoprenaline), 7.26 ± 0.04 (noradrenaline), 7.26 ± 0.05 (adrenaline), 7.79 ± 0.03 (BRL37344) and 6.74 ± 0.03 (CGP12177A), respectively, and all Schild slopes were not significantly different from unity. These results suggest that atypical β-adrenoceptors mediating relaxant responses of these agonists in the guinea pig gastric fundus are β<sub>3</sub>-adrenoceptors rather than putative β<sub>4</sub>-adrenoceptors.
Lack of Reinforcing Effect of the Benzodiazepine and Tricyclic Antidepressant Combination of Diazepam and Dothiepin
Authors: Oittinen Henna , Rameis Heinz , Saria Alois , Zernig Gerald 
Published: April 2003

Fixed combinations of a tricyclic antidepressant (TCA) with a benzodiazepine (BZD) for the treatment of depressive syndromes enjoy remarkable acceptance among patients and prescribing physicians. In order to investigate if the widespread use of one such fixed TCA-BZD combination might be due to its high positive reinforcing effect, we tested each drug alone and in combination in an operant conditioning paradigm (fixed ratio 1 time-out 150 s) of intravenous self-administration in rats and compared their reinforcing effects to that of cocaine. Diazepam proved to be of only moderate reinforcing strength. Dothiepin alone was ineffective as a reinforcer but essentially abolished the reinforcing effect of diazepam when given in combination with it. These data indicate that the widespread acceptance of the fixed diazepam-dothiepin combination by the therapeutic community is not due to an increase in the positive reinforcing effect of diazepam by dothiepin but that, in contrast, addition of dothiepin might even decrease diazepam’s moderately positive reinforcing effect.
Encapsulation in Cationic Liposomes Enhances Antitumour Efficacy and Reduces the Toxicity of Etoposide, a Topo-Isomerase II Inhibitor
Authors: Sengupta S. , Tyagi P. , Chandra S. , Kochupillai V. , Gupta S.K. 
Published: April 2003

Etoposide exerts its antineoplastic effect by forming a ternary complex with topo-isomerase II and DNA, leading to DNA breaks and cell death. However, it causes myelosuppression and its lipophilicity poses a major limitation during administration. Liposomes have been reported to increase the efficacy and reduce the toxicity of antineoplastic agents. Recent evidence suggests that cationic liposomes bind efficiently to tumours. The present study was thus designed to encapsulate etoposide in cationic liposomes and to evaluate its antitumour efficacy and systemic toxicity in comparison with a conventional parenteral formulation. Etoposide encapsulated in liposomes was synthesised by thin film hydration followed by an extrusion method. Fibrosarcoma was induced in mice by subcutaneous administration of 20-methylcholanthrene. Chemotherapy was started when the tumour reached 200 mm<sup>3</sup> in volume. Liposomal etoposide (10 mg/m<sup>2</sup>/day for 5 days) significantly delayed tumour growth as compared to non-liposomal etoposide. The median time of death was calculated to be 19.5, 26.25 and 56 days in vehicle-treated controls, non-liposomal-etoposide- and liposomal-etoposide-treated groups, respectively. A transient reduction in body weight was seen in both the liposomal- and non-liposomal-etoposide-treated groups. The maximum tolerated dose was however significantly higher in the group treated with liposomal etoposide, which also exhibited a lesser degree of myelosuppression than the animals treated with non-liposomal etoposide. The present findings suggest that cationic liposomes could be considered as potential for delivery of etoposide to tumours.