bluuebunny/crossref_metadata_2025_split huggingface dataset:
RPE in Perfusion Tissue Culture and Its Response to Laser Application
Authors: Framme Carsten , Kobuch Karin , Eckert Elfriede , Monzer Jan , Roider Johann 
Published: April 2003

<i>Purpose:</i> To study the effects of conventional laser application on the retinal pigment epithelium (RPE) in a perfusion tissue culture model of porcine retinal pigment epithelium without overlying neurosensory retina. <i>Methods:</i> RPE with underlying choroid was prepared from enucleated porcine eyes and fixed in a holding ring (Minusheet<sup>®</sup>). Specimens were then placed in two-compartment tissue culture containers (MinuCell &#38; Minutissue, Bad Abbach, Germany) and were cultured during continuous perfusion with culture medium at both sides of the entire specimen, the upper RPE and the lower choroid (12 specimens out of 6 eyes). Cultures were kept for 1, 3, 7 and 14 days and were examined histologically. Laser treatment was performed on each tissue ring by application of 3 × 3 laser burns one day after culture began (argon ion laser, wavelength: 514 nm, pulse duration: 100 ms; spot size: 200 µm) using different energy levels (400–1,000 mW); (16 specimens out of 8 eyes). <i>Results:</i> During laser treatment a marked lightening of the RPE with centrifugal spreading was observed. Using higher levels of energy, a contraction of the RPE towards the center of the laser spot was noticed. One day after laser photocoagulation histology revealed destruction of RPE; within 3–7 days of culture, migration and proliferation of neighboring cells was observed in several lesions. After 7 days the initial defect of the irradiated area was covered with dome shaped RPE cells and after 14 days multilayered RPE cells were showing ongoing proliferation. However, there were also cases without proliferation after laser treatment. The non-treated, continuously perfused RPE showed regular appearance in histological sections: during the first 7 days of culture, light microscopy revealed a normal matrix with a well-differentiated RPE monolayer. Subsequently proliferation even without treatment was observed and after 14 days the RPE became multilayered. <i>Conclusion:</i> It was possible to study the early healing response to the effect of laser treatment using the permanently perfused tissue culture system. A marked proliferation and repair of the laser defect could be observed in several but not all lesions. After 14 days even without laser treatment a proliferative multilayered RPE was present. Although this limits the use of the system for longer than 7 days, it seems to be useful for investigation of RPE-related disorders.
Split Cord Malformation in Two Sisters
Authors: Erşahin Yusuf , Kitiş Ömer , Öner Kazim 
Published: April 2003

Split cord malformations (SCMs) are uncommon congenital spinal anomalies and are seen mostly in females. SCMs in siblings are extremely rare. We report two sisters with SCM. These 10- and 8-year-old girls were the first and second children, respectively, of nonconsanguineous parents. Both sisters had a hypertrichosis and pes cavus deformity. The first child had a type I SCM and the second a type II SCM. They had additional spinal lesions, with tethering of the spinal cord. They were operated on and showed an uneventful postoperative course. All reported siblings with SCM have been female. The present data are not sufficient to account for the sex predilection. Therefore, further data and knowledge are needed.
Docetaxel in Combination with Dacarbazine in Patients with Advanced Melanoma
Authors: Bafaloukos D. , Aravantinos G. , Fountzilas G. , Stathopoulos G. , Gogas H. , Samonis G. , Briasoulis E. , Mylonakis N. , Skarlos D.V. , Kosmidis P. 
Published: April 2003

<i>Objectives:</i> The number of agents that are active in patients with metastatic melanoma is limited and cure is not a realistic objective for treatment at this stage. The aim of the study was to evaluate the efficacy and safety of new combination regimen cosisting of docetaxel and dacarbazine (DTIC), as first-line chemotherapy, in patients with advanced melanoma. <i>Patients and Methods:</i> Patients with advanced melanoma (including cerebral metastases) were eligible. Docetaxel 80 mg/m<sup>2</sup>, i.v. over 1 h infusion on day 1, and DTIC 400 mg/m<sup>2</sup>, i.v. over 45 min on days 1 and 2, were given every 21 days, for six cycles. All patients were premedicated, prior to each course, with methylprednisolone per os. <i>Results:</i> Forty-one patients entered the study. Thirty-nine were assessable for response and 40 for toxicity. Objective responses were seen in 10 patients (24% of the eligible; 95% CI = 12.4–40.3%, 26% of the assessable and 28% of patients with cerebral metastases were excluded). Three of them achieved a complete response (7%; 95% CI = 1.5–19.9) and 7 a partial response (17%; 95% CI = 7.1–32.0), while 8 patients demonstrated stabilization of their disease (20%; 95% CI = 8.8–34.9). After a median follow-up of 20 months, the median time to progression was 7 months (range 0.5–22) and the median survival was 10 months (1–24+). The main toxicity (G3–4) was neutropenia which occurred in 8/40 (20%) patients. Additional patients had reversible G3–4 toxicities including alopecia, nausea and vomiting and fatigue; 3 of them presented mild to moderate hypersensitivity reactions to docetaxel. No toxic death was noted. <i>Conclusions:</i> The combination of docetaxel and DTIC is active and well tolerated in patients with advanced melanoma. While this combination is at least as effective as various combination regimens, it does not differ from that reported for single-agent DTIC.
N-Methyl-L-Serine Stimulates Hyaluronan Production in Human Skin Fibroblasts
Authors: Sakai Shingo , Sayo Tetsuya , Kodama Shuji , Inoue Shintaro 
Published: April 2003

We examined the effects of <i>N</i>-methyl-L-serine (NMS), an amino acid derivative, on hyaluronan (HA) synthesis in human skin fibroblasts. NMS (1–10 m<i>M</i>), but not L-serine, stimulated the incorporation of [<sup>3</sup>H]glucosamine into HA dose-dependently, with a maximum stimulation of 1.5-fold compared to the control. The effect of NMS was specific for HA production, because there was no change in sulfated glycosaminoglycan formation. Neither the <i>N</i>-methyl derivatives of L-glycine or L-alanine, nor <i>N</i>-methyl-D-serine, could stimulate HA synthesis, indicating that the β-hydroxyl group and the L-configuration were essential for the activity. Gel filtration of the products showed that NMS stimulated the production of high-molecular-mass HA (>10<sup>6</sup> D) without affecting the production of low-molecular-mass HA. NMS required 24 h to stimulate HA production, and when fibroblasts were pretreated for 10–24 h with NMS (1–10 m<i>M</i>), membrane-associated HA synthase activity was increased dose-dependently. Thus, a second messenger is likely to be involved in the stimulation of HA production by NMS.
Nephrotic Proteinuria as a Result of Essential Hypertension
Authors: Obialo Chamberlain I. , Hewan-Lowe Karlene , Fulong Brenda 
Published: April 2003

<i>Background:</i> The presence of nephrotic-range proteinuria in a nondiabetic hypertensive patient is generally indicative of an underlying glomerular disease. A few published reports have noted nephrotic proteinuria in some patients with hypertensive nephrosclerosis. The frequency of this association is unknown. <i>Methods:</i> We retrospectively reviewed renal biopsy reports on all cases of nephrotic syndrome over an 8-year period (1993–2000). We excluded all cases of diabetes mellitus, lupus, hepatitis, human immunodeficiency virus, and chronic use of nonsteroidal anti-inflammatory drugs. Biopsy specimens showing glomerular eosinophilic hyalinosis lesions, positive immunofluorescence staining, or dense deposits on electron microscopy were also excluded. Thirteen of the remaining 237 (5.5%) biopsy specimens satisfied the standard histological criteria for hypertensive nephrosclerosis. <i>Results:</i> All patients were African-Americans with a mean age of 47.5 ± 13 years and an average mean arterial blood pressure of 122 ± 19 mm Hg. The mean values for urinary protein excretion, serum creatinine, albumin, and cholesterol were 8.9 g/day, 3.3 mg/dl, 3.1 g/dl, and 245 mg/dl, respectively. Optimal blood pressure control required at least three antihypertensive agents. Progression to end-stage renal disease occurred over a mean duration of 8.3 ± 6.5 months. Multivariate regression showed a strong but nonsignificant association between the level of proteinuria at the time of biopsy, duration of hypertension, and number of blood pressure medications (R<sup>2</sup> = 0.56, p = 0.38). <i>Conclusions:</i> Nephrotic syndrome may be more common in poorly controlled essential hypertension than previously realized. In African-American patients, the differential diagnosis of nephrotic syndrome should include hypertensive nephrosclerosis, but abrogation of renal biopsy is not implied.
Body-Weight-Independent Dosing of Cyclosporine Micro-Emulsion and Three Times Weekly Maintenance Regimen in Severe Psoriasis
Authors: Thaçi D. , Bräutigam M. , Kaufmann R. , Weidinger G. , Paul C. , Christophers E. 
Published: April 2003

<i>Background:</i> Body-weight-dependent (BWD) treatment of psoriasis with cyclosporine A (CsA is well established. It has recently been reported that this is not necessary for the treatment of atopic dermatitis. <i>Objectives:</i> (1) To investigate the efficacy and safety of a CsA micro-emulsion administered in a new body-weight-independent (BWI) protocol and to compare it to a BWD dosage regimen in the treatment of severe psoriasis. (2) To investigate the duration of disease remission after intermittent treatment of psoriasis with CsA. <i>Patients and Methods:</i> 122 adult patients with severe plaque-type psoriasis (PASI ≧12) were included in this study which consisted of two treatment periods: period I was a randomised parallel-group comparison of daily CsA doses of 100–300 mg (BWI) or 1.25–5.0 mg/kg (BWD) for 12 weeks; period II was a randomised double-blind placebo-controlled extension treatment of patients, who had responded (>75% PASI recovery) to the treatment in period I and continued the treatment on their last effective dose or placebo 3 times weekly for a further 12 weeks. <i>Results:</i> In period I, the increase in creatinine in the BWI group (2.7 µmol/l) was proven to be non-inferior to that of the BWD group (3.5 µmol/l) at a non-inferiority limit of 5 µmol/l (p < 0.05). The PASI decreased with BWI dosing from 22.0 to 3.0 and with the BWD scheme from 19.5 to 2.5 (p = 0.98). In period II, the relapse rates were 40.5% (17/42) with intermittent CsA and 56.9% (29/51) with placebo (p = 0.15). <i>Conclusions:</i> BWI dosing is as effective and safe as conventional BWD dosing for the short-term treatment of severe psoriasis. There was a tendency toward a prolongation of remission with intermittent CsA treatment.
Does Growth Hormone Treatment Alter Skeletal Muscle Mitochondrial Respiration in Rats?
Authors: Peyreigne C. , Raynaud E. , Fedou C. , Prefaut C. , Brun J.-F. , Mercier J. 
Published: April 2003

<i>Objective:</i> Growth hormone (GH) has been shown to stimulate lipolysis and enhance lipid oxidation. We investigated whether GH could improve mitochondrial oxidative capacity. <i>Method:</i> Fourteen male Wistar rats received 14-day treatment with biosynthetic human GH (10 IU/kg/24 h) or placebo. Mitochondria were isolated from the total muscle of one hind limb of the rat. Mitochondrial oxygen consumption was measured in vitro using a Clark-type electrode with three substrates: palmitoyl-<i>L</i>-carnitine, pyruvate and succinate (+ rotenone). <i>Results:</i> Muscle mitochondrial yield was not significantly different in the GH-treated group from that in controls. Neither the basal nor ADP-stimulated respiratory state reached a significant difference between the 2 groups with palmitoyl-<i>L</i>-carnitine, pyruvate, and succinate. <i>Conclusion:</i> GH treatment did not improve the oxidative capacity of skeletal muscle mitochondria.
An Immunohistochemical Assessment of the Response of the Psoriatic Lesion to Single and Repeated Applications of High-Dose Dithranol Cream
Authors: Swinkels O.Q.J. , Prins M. , Gerritsen M.J.P. , van Vlijmen-Willems I.M.J.J. , van der Valk P.G.M. , van de Kerkhof P.C.M. 
Published: April 2003

Dithranol, although a time-honoured treatment and from the beginning of the previous century still going strong, remains an empirical treatment. There is growing evidence that the biochemical basis for the mechanism of action of dithranol at the molecular level is related to the redox activity leading to the production of active oxygen species, which include singlet oxygen, superoxide anion radical and hydroxyl radical. Some authors suggest that epidermal proliferation and/or keratinisation may be the target for dithranol, while others refer to aspects of cutaneous inflammation as crucial in the antipsoriatic effect of dithranol. The present study aims to analyse the effect of single and repeated applications of dithranol on aspects of epidermal proliferation, keratinisation and inflammation in the psoriatic plaque. The most marked effect of dithranol proved to be that on epidermal proliferation (the number of Ki-67-positive nuclei) with an early reduction already 1 day following the single application. This reduction lasted for 16 days. However, such an application induced only a modest clinical improvement. Repeated challenges, resulting in a decrease in the number of Ki-67-positive nuclei of 66%, led to a substantial clinical improvement after 12 days. Repeated challenges resulted in a significant reduction of the number of polymorphonuclear leucocytes. However, this reduction was less pronounced as compared to the effect on epidermal proliferation. It is concluded that epidermal proliferation is a sensitive marker to demonstrate an early effect of dithranol. The dynamics of the cell-biological responses suggest that intermittent applications might be a promising new approach. As dithranol does not reduce the number of T lymphocytes, it is attractive to speculate that the combination of dithranol with immunosuppressive treatments might be a very effective combination.
Monoclonal Antibodies against Blo t 13, a Recombinant Allergen from <i>Blomia tropicalis</i>
Authors: Labrada Mayrel , Uyema Keiko , Sewer Minerva , Labrada Alexis , González Maritza , Caraballo Luis , Puerta Leonardo 
Published: April 2003

<i>Background:</i> The recombinant allergen of <i>Blomia tropicalis</i>, rBlo t 13, shows 11% of IgE reactivity to sera from allergic patients. This allergen belongs to the fatty acid-binding protein family and its natural equivalent remains to be isolated. Monoclonal antibodies (MAbs) are important tools for specific determination and isolation of natural allergens as well as for characterization of recombinant proteins. <i>Methods:</i> Mice were immunized with partially purified preparation of rBlo t 13 allergen expressed in the yeast <i>Pichia pastoris</i>. Spleen cells were fused with myeloma cells using polyethylene glycol. Hybridoma screening was performed using a direct ELISA with recombinant allergen. MAb specificity to rBlo t 13 was tested by immunoblotting. Topography of binding sites and binding of MAb to native allergen was studied by ELISA. Reactivity of MAb against allergenic extract of <i>B. tropicalis</i> and <i>Dermatophagoides siboney</i> was analyzed by ELISA inhibition. In addition, the reactivity of MAbs against rBlot 13 from <i>Escherichia coli</i> and <i>P. pastoris </i>expression was compared. <i>Results:</i> Two MAbs, 5G3 and 3G4 with IgG1 isotype, were generated. These MAbs specifically recognized the 16-kD band, which corresponds to the molecular weight shown by rBlo t 13 on SDS-PAGE. In ELISA, the binding of 5G3 MAb to <i>B. tropicalis</i> and <i>D. siboney </i>extracts was inhibited by rBlo t 13. Both MAbs showed the highest reactivity when the allergen was expressed in <i>P. pastoris. </i><i>Conclusion:</i> Two MAbs specific for Blo t 13 were obtained. These MAbs recognized the same or close epitopes on the rBlo t 13 molecule. The occurrence of homologous allergens to Blo t 13 in <i>D. siboney</i> is suggested by the ELISA inhibition assay.
Protein Kinase C Beta Isoenzymes in Diabetic Kidneys and Their Relation to Nephroprotective Actions of the ACE Inhibitor Lisinopril
Authors: Pfaff Imke L. , Vallon Volker 
Published: April 2003

Inhibitors of angiotensin-converting enzyme (ACE) or beta isoforms of protein kinase C (PKC) are nephroprotective in diabetes mellitus. We investigated the influence of streptozotocin (STZ)-induced diabetes mellitus and of treatment with the ACE inhibitor lisinopril (4 mg/kg p.o. twice daily for 4 weeks) on the expression of PKC beta 1 and PKC beta 2 in the renal cortex of female Sprague-Dawley rats. Immunohistochemistry indicated an enhanced renocortical accumulation of macrophages expressing both MHC II, a marker for antigen-presenting cells, as well as PKC beta 2 in STZ diabetes which was confirmed by Western blotting demonstrating an enhanced renocortical expression of MHC II (1.8-fold) as well as of membrane-associated PKC beta 2 (1.9-fold). Whereas immunohistochemistry could not detect unequivocal alterations, Western blotting showed a rise in the renocortical expression of membrane-associated PKC beta 1 (1.7-fold) in STZ diabetes. Lisinopril lowered renocortical albumin content and proteinuria in STZ diabetes and attenuated the enhanced accumulation of macrophages expressing PKC beta 2 as well as the increase of membrane-associated expression of PKC beta 1 and PKC beta 2 in the renal cortex. The data suggest that the nephroprotective actions of the ACE inhibitor lisinopril in experimental diabetes mellitus were associated with and thus could be mediated in part by inhibition of diabetes-induced activation of PKC beta isoenzymes in the renal cortex.
Renal Hemodynamics during Development of Hypertension in Young Spontaneously Hypertensive Rats
Authors: Christiansen Rolf E.F. , Roald Anca B. , Tenstad Olav , Iversen Bjarne M. 
Published: April 2003

<i>Background/Aims:</i> Cross-transplantation studies between animals with genetic hypertension and normotensive animals indicate a key role of the kidney in development of hypertension, and studies in young spontaneously hypertensive rats (SHR) have shown reduced glomerular filtration rate (GFR) and renal blood flow (RBF) for a short period at the age of 4–6 weeks during blood pressure increase. We tested the hypothesis that a decline in GFR during development of hypertension in SHR might be more pronounced in juxtamedullary cortex than other cortical zones. <i>Methods:</i> By use of the aprotinin method, total and zonal cortical GFR was measured in anaesthetized Wistar-Kyoto (WKY) rats and SHR at the ages of 2, 4, 6, 8 and 10 weeks. RBF was measured by a transit time flowmeter. <i>Results:</i> Body and kidney weights in SHR and WKY were not significantly different in any age group (p >0.05). Mean arterial blood pressure (MAP) was not different at the age of 2 weeks (79 ± 6 mm Hg in SHR and 74 ± 5 mm Hg in WKY, p > 0.05), but was significantly higher in 4-week-old SHR (104 ± 1 mm Hg) compared to 4-week-old WKY (77 ± 3 mm Hg) (p < 0.01). The difference in blood pressure increased with age from 4 to 10 weeks. RBF, total GFR, and outer, middle, and inner cortical GFR increased with age but were not different in SHR and WKY in any age group (p >0.05). Renal vascular resistance was increased from 4 weeks of age in SHR (21.5 ± 1.8), significantly higher than WKY (14.4 ± 0.9 mm Hg·ml<sup>–1</sup>·min·g) (p < 0.01) and stayed at higher values in older age groups (p ≤ 0.01). <i>Conclusion:</i> RBF, total and zonal GFR are not significantly different in anaesthetized SHR compared to WKY at ages from 2 to 10 weeks and GFR in juxtamedullary cortex is not decreased in SHR during onset of hypertension. The results from the present study indicate that development of hypertension cannot be explained by a temporary decline in RBF or total or zonal GFR.
Modified Protocols for Surfactant Therapy in Experimental Meconium Aspiration Syndrome
Authors: Tashiro Katsumi , Cui Xiao-Guang , Kobayashi Tsutomu , Curstedt Tore , Robertson Bengt 
Published: April 2003

In adult rats with experimental meconium aspiration syndrome, we investigated whether the therapeutic effect of exogenous surfactant was increased by addition of dextran or preceding airway lavage with diluted surfactant. Animals (n = 72) ventilated with pure oxygen were given human meconium suspension (50–75 mg kg<sup>–1</sup>) through the airways. When the PaO<sub>2</sub> had decreased to <20 kPa (mean ± SD 12 ± 3.9 kPa), the rats were randomly allocated to ten groups (G). G 6–10 underwent lung lavage with diluted Curosurf (5 mg ml<sup>–1</sup>, 20 ml kg<sup>–1</sup>), whereas G 1–5 did not. G 1 and 6 received no additional material through the airways. G 2 and 7 received Curosurf (100 mg kg<sup>–1</sup>), and G 3 and 8 received Curosurf (100 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>); G 4 and 9 received Curosurf (200 mg kg<sup>–1</sup>), and G 5 and G 10 received Curosurf (200 mg kg<sup>–1</sup>) plus dextran (75 mg kg<sup>–1</sup>). All rats in G 1 died before 180 min after randomization. In G 2, 3, 6, 7, and 8, the PaO<sub>2</sub> transiently increased to 30–40 kPa. In G 4, 5, 9, and 10, the PaO<sub>2</sub> remained >30 kPa for 180 min. Both airway lavage and supplementation with dextran improved the therapeutic effects of surfactant; however, a large dose (200 mg kg<sup>–1</sup>) was nevertheless required to optimize gas exchange.
Endothelin-A Receptor Antagonist BQ-485 Protects against Intraocular Pressure Spike Induced by Laser Trabeculoplasty in the Rabbit
Authors: Holló Gábor , Kóthy Péter , Lakatos Péter , Vargha Péter 
Published: April 2003

<i>Purpose:</i> We have previously shown in rabbits that the intraocular pressure (IOP) spike caused by argon laser trabeculoplasty (ALT) is associated with an acute endothelin-1 (ET-1) release from the uveal tissue into the aqueous humour. In this study we investigated whether pretreatment with an ET<sub>A</sub> receptor antagonist (BQ-485) protects against the pressure spike induced by ALT, in the rabbit model. <i>Methods:</i> Under general anaesthesia, 10 µl of 10<sup>–5</sup><i>M</i> BQ-485 was injected into the anterior chamber of the right eye, and 10 µl of balanced salt solution (BSS) into the contralateral anterior chamber, for 12 pigmented rabbits. Five minutes later ALT (1,000 mW, 0.1 s, 100 spots over 360° focused on the iris pillars) was performed on both eyes of each animal. IOP was measured before the injections (baseline value), and also 30 min afterwards using a Tono-Pen XL tonometer. Immediately after the second IOP measurement aqueous humour was aspirated for measurement of ET-1 concentration. <i>Results:</i> The baseline IOP (mean ± SD) was 8.08 ± 1.73 mm Hg and 7.92 ± 1.78 mm Hg for the right and left eyes, respectively (Duncan test, p > 0.05). At 25 min after ALT the IOP of the BQ-485-pretreated right eyes remained unchanged (7.83 ± 2.44 mm Hg, p > 0.05) but the IOP of the BSS-pretreated left eyes at 30 min increased significantly to 10.67 ± 4.70 mm Hg (p < 0.05 for comparisons both with the corresponding baseline value for the same eye, and with the IOP of the contralateral eye at 30 min). There was no difference in aqueous humour ET-1 concentration between the corresponding right and left eyes (paired t test, p > 0.05). <i>Conclusion:</i> Intracameral BQ-485 pretreatment protected against the ALT-induced acute IOP elevation, but did not influence the laser-induced ET-1 release. This suggests that ET<sub>A </sub>receptor antagonists may potentially have a therapeutic role in the prevention of laser-induced IOP spikes.