bluuebunny/crossref_metadata_2025_split huggingface dataset:
Corneal Toxicity of Xylazine and Clonidine, in Combination with Ketamine, in the Rat
Authors: Tita B. , Leone M.G. , Casini M.L. , Corubolo C. , Bordi F. , Guidolin D. , Fumagalli E. , Romanelli L. , Mattioli F. , Fehér J. , Saso L. 
Published: April 2003

<i>Purpose:</i> To compare the corneal toxicity of xylazine (XYL)/ketamine (KET) with that of clonidine (CLO)/KET in the rat, in the presence or not of the α<sub>2</sub>-adrenergic antagonist yohimbine (YOH). <i>Methods: </i>XYL (10 mg/kg) and CLO (0.15 mg/kg) were administered subcutaneously in the rat in combination with KET (50 mg/kg), in the presence or not of YOH (2 mg/kg). <i>Results:</i> The corneas immediately lost transparency and luster, but recovered within 120 min. By both light and electron microscopy, a marked stromal edema and alterations of all layers were observed. In addition, XYL/KET altered the permeability of the cornea as indicated by the augmented levels of <sup>14</sup>C-indomethacin, topically administered 30 min after the anesthetic combination. <i>Conclusions: </i>The mechanism of the corneal toxicity of XYL and CLO in the rat is unclear but we speculate that: (a) proptosis and inhibition of normal blinking did not play a major role because topical application of hyaluronic acid did not protect against it; corneal decompensation, edema and opacification could be due to (b) osmotic or (c) mechanical endothelial stress: the first resulting from the sudden increase of the glucose concentration in the aqueous humor due to the well-known inhibition of insulin release by α<sub>2</sub>-adrenergic agonists, and the second from the acute elevation of intraocular pressure caused by these α<sub>2</sub>-adrenergic mydriatics in the rat; (d) addition, XYL and CLO could act by directly interacting with local α<sub>2</sub>- or, possibly, α<sub>1</sub>-adrenergic receptors, whose function is still not clear but probably essential for corneal homeostasis.
TAS-301, a New Synthetic Inhibitor of Neointimal Thickening after Balloon Injury, Inhibits Calcium-Dependent Signal Transduction and Cytoskeletal Reorganization
Authors: Sasaki Eiji , Miyoshi Kazuhisa , Nozawa Yoshihisa , Kanda Atsuhiro , Nakano Kohshi , Yamasaki Yasundo , Miyake Hidekazu , Matsuura Naosuke 
Published: April 2003

We previously demonstrated that a recently synthesized drug, TAS-301 [3-bis(4-methoxyphenyl)methylene-2-indolinone], inhibited neointimal thickening after single-balloon injury to the rat common carotid artery by inhibiting both the migration and proliferation processes of vascular smooth muscle cells (VSMCs). The purpose of this current study was to elucidate the possible mechanism of action for its inhibition of the migration process of VSMCs. We also determined the efficacy of TAS-301 on second neointimal formation 14 days after a double-balloon injury to the rat common carotid artery. Neointimal thickening, 14 days after second balloon injury, was reduced by the oral administration of TAS-301 in a dose-dependent manner. In in vitro assays using rat VSMCs, Western blot analysis showed that TAS-301 inhibited platelet-derived growth factor (PDGF)-induced tyrosine phosphorylation of both focal adhesion kinase and paxillin. Tyrosine phosphorylation of these proteins depended on the increment of intracellular calcium concentration ([Ca<sup>2+</sup>]<sub>i</sub>). The PDGF-induced elevation of [Ca<sup>2+</sup>]<sub>i</sub> and activation of Ca<sup>2+</sup>/calmodulin-dependent protein kinase II (CaM kinase II) were also inhibited by TAS-301. Additionally, TAS-301 at 10 µmol/l reduced the extent of F-actin stress fiber depolymerization observed in response to PDGF. These results indicate that TAS-301 reduced the intimal thickening after denudation to a pre-existing lesion to the same extent as it reduced that after a single-balloon injury to the normal artery. Furthermore, the results of our in vitro experiments suggest that antimigratory mechanisms of TAS-301 that contribute to preventing the intimal thickening might be mediated by drug inhibition of Ca<sup>2+</sup>-dependent signal molecules and the following cytoskeletal depolymerization.
Alteration of Drug Kinetics in Rats following Exposure to Trichloroethylene
Authors: Kukongviriyapan Veerapol , Simajareuk Suthanee , Kukongviriyapan Upa , Cha-on Ubon , Airarat Wanchai 
Published: April 2003

The effect of trichloroethylene (TCY) was investigated to determine whether repeated exposure alters the pharmacokinetics of some drugs. Sprague-Dawley rats were given intraperitoneal injections of TCY (5 mmol/kg) in corn oil once daily for 3 days, while the control group received only corn oil. Four hours after the last dose, theophylline, quinidine, or pentobarbital were administered. Blood samples were collected at appropriate intervals for drug analyses. There was a small decrease in plasma clearance of theophylline, with no change in volume of distribution (V<sub>d</sub>) as compared with controls. For quinidine, the elimination half-life was unchanged, and the V<sub>d</sub> was decreased by 40%. The clearance of pentobarbital was decreased by 40% in male rats, but not in the females. Nonetheless, the duration of the sleeping time for both sexes was remarkably prolonged as compared with the control group. There was a decrease in the cytochrome P-450 content only in male rats. In conclusion, exposure to TCY causes changes in some drug kinetics, probably resulting from differential effects on the drug-metabolizing enzymes.
NMP 22, BTA stat Test and Cytology in the Diagnosis of Bladder Cancer: A Comparative Study
Authors: Gutiérrez Baños J.L. , Rebollo Rodrigo M.H. , Antolín Juárez F.M. , Martín García B. 
Published: April 2003

<i>Objective:</i> To evaluate the usefulness of the NMP 22 and BTA stat test in the diagnosis and follow-up of bladder cancer and to compare these tests to cytology and cystoscopy, routine diagnostic methods. <i>Methods:</i> 150 patients followed up for bladder cancer or symptoms suggestive of bladder cancer underwent cystoscopy after cytology, NMP 22 and BTA stat test using a recently voided urine sample. In suspect cases, TUR and histopathological analysis were performed. <i>Results:</i> Bladder cancer was proven in 76 patients and excluded in 74. For NMP 22 we have used the cutoff value recommended by the manufacturer (10 U/ml) and that obtained by our receiver-operating characteristic curve (6 U/ml). Sensitivity was 84.21% for NMP 22 at the cutoff value of 6 U/ml and 76.32% with 10 U/ml; 72.37% for BTA stat test; 69.74% for cytology, and 100% for cystoscopy. Specificity was 86.49% for NMP 22 at a cutoff value of 6 U/ml and 90.54% at 10 U/ml; 89.19% for the BTA stat test; 93.24% for cytology and 89.19% for cystoscopy. NMP 22 sensitivity for grades 1, 2, and 3 was 68.75, 75.86 and 100%, respectively, at a cutoff value of 6 U/ml, and 50, 68.97 and 96.77%, respectively, at a cutoff level of 10 U/ml; for BTA stat the sensitivity was 56.25% in G1, 62.07% in G2 and 90.32% in G3, and for cytology the sensitivity was 43.75, 62.07 and 90.32%, respectively. The sensitivity of NMP 22 was 68.75% in stage Ta, 84.78% in T1 and 100% in T2–T4 at a cutoff level of 6 U/ml and 50, 80.43 and 92.86%, respectively, at a cutoff level of 10 U/ml; BTA stat sensitivity was 50% in Ta, 73.91% in T1 and 92.86% in T2–T4; and in cytology the results were 37.50, 73.91 and 85.71%, respectively. Using the McNemar test, there was only a significant difference between the sensitivity of NMP 22 at a cutoff level of 6 U/ml and cytology in the overall sample. <i>Conclusions:</i> The high sensitivity of the NMP 22 and BTA stat test in combination with the data obtained from the parameters used for the evaluation of the test demonstrate their usefulness in the diagnosis and follow-up of bladder cancer. NMP 22 at a cutoff value of 6 U/ml is significantly more sensitive than cytology and consequently a thoroughly valid diagnostic tool in the diagnosis of bladder cancer which may substitute voided urine cytology.
A Neuroactive Steroid, Pregnenolone, Alters the Striatal Dopaminergic Tone before and after Puberty
Authors: Muneoka Katsumasa T. , Takigawa Morikuni 
Published: April 2003

Neuroactive steroids are known to modulate excitability in neurons. Neuronal activity during early development is critical to normal development of the brain. A neuroactive steroid, pregnenolone, was administered (10 µg/g) to rats from postnatal day 3 (PD 3) through PD 7. Dopamine (DA), serotonin (5-HT) and their metabolites were measured in the striatum. The results showed that neonatal treatment with pregnenolone increases DA and 5-HT turnover in the striatum at 3 weeks of age. The increased 5-HT turnover in the pregnenolone-treated animals was normalized at 14 weeks of age whereas the DA turnover in the pregnenolone-treated group was lower than in the control group. The present study indicated that pregnenolone treatment during the neonatal period induced abnormal development of the striatal dopaminergic function in adulthood.
Corticomedullary Procollagen α1(IV) mRNA Levels and Localization after Subtotal Nephrectomy
Authors: Adler Sharon G. , Lee Grace S. , Cohen Arthur H. , Nast Cynthia C. 
Published: April 2003

The relationships between tubular hypertrophy/hyperplasia, procollagen α1(IV) mRNA levels, and the development of tubular basement membrane thickening were studied in male Sprague-Dawley rats subjected to subtotal renal ablation and sacrificed 2 or 15 days later. Tubular hypertrophy and hyperplasia were demonstrable at 2 days, however no increment in procollagen α1(IV) mRNA levels was discerned at that time, demonstrating a dissociation between mRNA levels for classical type IV collagen and tubular enlargement. At 15 days, tubular procollagen α1(IV) mRNA levels did increase approximately 2-fold (p < 0.002), localizing predominantly in proximal tubules in the deep cortex and outer medullary stripe. At this time point, there was still no significant correlation to tubular enlargement, but there was a significant correlation to tubular basement membrane thickening (r = 0.89, p < 0.01). These studies demonstrated that an increase in mRNA for classical type IV collagen is not required for the development of hypertrophy, and that the increment is a better marker for matrix expansion than it is for hypertrophy.
Randomized Trial of Methylcobalamin and Folate Effects on Homocysteine in Hemodialysis Patients
Authors: Trimarchi Hernán , Schiel Amalia , Freixas Emilio , Díaz Marisa 
Published: April 2003

<i>Background:</i> There are no data available on the effects of intravenous (i.v.) methylcobalamin (Me-Cbl), the coenzymatically active form of vitamin B<sub>12</sub> that acts as a cofactor for methionine synthase in the conversion of total homocysteine (tHcy) to methionine, with or without oral folic acid (FA) supplementation, on fasting tHcy levels in hemodialysis (HD) patients. <i>Methods:</i> We performed a prospective randomized trial in which 62 chronic HD patients without previous vitamin supplementation were divided into four groups. Group A received Me-Cbl 500 µg twice/week plus FA 10 mg/day; group B received FA 10 mg/day alone; group C received no vitamin supplementation, and group D was on Me-Cbl 500 µg twice/week alone. Fasting tHcy, vitamin B<sub>12</sub>, serum (s) FA and erythrocytic (e) FA were measured predialysis before and after 4 months of therapy. <i>Results:</i> Final tHcy levels were significantly lower in group A (10.2 ± 3.1 µmol/l) compared to groups C (27.3 ± 9.7 µmol/l, p < 0.001) and group D (24.3 ± 11.8 µmol/l, p < 0.001) and similar to group B (11.2 ± 1.9 µmol/l, p = n.s.). Mean tHcy levels showed a significant decrease in group A from 22.5 ± 15.6 to 10.2 ± 3.1 µmol/l (p = 0.003) and in group B from 19.9 ± 4.0 to 11.2 ± 1.9 µmol/l (p = 0.012), while no significant changes were observed in groups C (25.9 ± 9.3 vs. 27.3 ± 9.7 µmol/l, p = n.s.) and D (26.6 ± 14.3 vs. 24.3 ± 11.8 µmol/l, p = n.s.). <i>Conclusion:</i> Oral FA (10 mg/day) supplementation appears to be an effective approach to normalize plasma tHcy in chronic HD patients; the addition of i.v. Me-Cbl (500 µg twice/week) to this regimen showed no benefit. Separately, FA corrected hyperhomocysteinemia (HtHcy), while Me-Cbl showed no change.
Urinary Excretion of Aquaporin-2 Water Channel in Diabetic Ketoacidosis
Authors: Kusaka Ikuyo , Saito Takako , Nakamura Tomoatsu , Nagasaka Shoichiro , Ishibashi Shun , Ishikawa San-e 
Published: April 2003

We studied the changes in plasma arginine vasopressin (AVP) and urinary excretion of aquaporin-2 (UAQP-2) water channel in 3 patients with diabetic ketoacidosis. They had marked hyperglycemia of 27.9 ± 2.8 mmol/l (mean ± SEM), and elevated hemoglobin A1c of 8.8 ± 1.4%. Circulatory blood volume was decreased by approximately 25%, which was determined by the changes in hematocrit. Plasma AVP levels were elevated to 10.3 ± 3.0 pmol/l and UAQP-2, 578 ± 200 fmol/mg creatinine (normal, 153 ± 28) at the hospitalization. When hyperglycemia was improved by the intravenous infusion of a small dose of insulin plus fluid administration, both plasma AVP and UAQP-2 promptly decreased to 1.2 ± 0.2 pmol/l and 252 ± 29 fmol/mg creatinine on day 7, respectively. These alterations were concomitant with the recovery of circulatory blood volume. In the present study, UAQP-2, in addition to plasma AVP, indicates circulatory blood volume depletion, and the changes in UAQP-2 estimates the AVP-dependent recovery of circulatory blood volume during the therapeutic period in the patients with diabetic ketoacidosis.
Insulin-Like Growth Factors and Insulin-Like Growth Factor Binding Proteins in Adult Patients with Severe Liver Disease before and after Orthotopic Liver Transplantation
Authors: Weber Matthias M. , Auernhammer Christoph J. , Lee Phillip D.K. , Engelhardt Dieter , Zachoval Reinhart 
Published: April 2003

<i>Introduction:</i> The liver is the main source of serum insulin-like growth factors (IGFs) and IGF-binding proteins (IGFBPs) and the concentration of these proteins might reflect liver function. <i>Methods:</i> In a retrospective longitudinal study we examined serum levels of total and free IGF-I, IGF-II, IGFBP-1, IGFBP-2, IGFBP-3 and IGFBP-6 in 21 adult patients with end-stage liver disease before and after orthotopic liver transplantation (LTX) by sensitive and specific RIAs. In each patient, the mean value of at least three measurements before and after LTX was calculated. <i>Results:</i> Before LTX, serum levels of total and free IGF-I, IGF-II, IGFBP-3 were low and showed a rapid and significant increase in almost all patients after successful LTX (total IGF-I: 30 ± 7 vs. 256 ± 30 ng/ml, p < 0.001; free IGF-I: 1.3 ± 0.3 vs. 3.5 ± 0.6 ng/ml, p < 0.01; IGF-II: 177 ± 28 vs. 618 ± 30 ng/ml, p < 0.001; IGFBP-3: 1,230 ± 136 vs. 3,665 ± 264 ng/ml, p < 0.001). In contrast, IGFBP-1 was found to be high immediately before LTX, and declined to normal levels after LTX (210 ± 40 vs. 90 ± 15 ng/ml, p < 0.01), while IGFBP-2 did not show any significant changes (1,154 ± 296 vs. 1,303 ± 192 ng/ ml). Positive correlations were found between IGF-I, IGF-II or IGFBP-3, and serum pseudocholinesterase (R = 0.50, 0.72 and 0.61 respectively, p < 0.001). Negative correlations were found between IGF-I, IGF-II or IGFBP-3, and prothrombin time (R = 0.50, 0.59 and 0.51 respectively, p < 0.001). <i>Conclusion:</i> Patients with severe liver disease show decreased levels of total and free IGF-I, IGF-II and IGFBP-3, and increased levels of IGFBP-1. These abnormalities are promptly normalized after successful LTX. Thus, serum levels of IGF-I, IGF-II and IGFBP-3 might be useful parameters for the assessment of liver function.
Study of the Patch Test Reactions to <i>Myocoptes musculinus</i> (Kekuidani) of NC/F Mice (Atopic Model Mice)
Authors: Sugiura Keiji , Sugiura Mariko , Hayakawa Ritsuko , Shamoto Mikihiro , Takahashi Hisahide 
Published: April 2003

<i>Background:</i> Atopic dermatitis is considered to be developed by the IgE-mediated immediate allergy and by the delayed hypersensitivity to causative allergens. We have previously reported that IgE-mediated type I allergy to mites contributed to the development of skin eruptions on atopic model mice (NC mice). <i>Objective:</i> This time, we studied the delayed hypersensitivity skin reaction to mites in NC/F mice. <i>Methods:</i> We conducted 48-hour closed patch testing with <i>Myocoptes musculinus</i> (kekuidani) that is a parasite in NC/F mice and BALB/C mice. <i>Results:</i> At both the 48- and 72-hour readings, 7 (87.5%) out of 8 NC/F mice tested showed positive reactions to <i>M. musculinus</i>. All BALB/C mice showed negative reactions to <i>M. musculinus</i>. All animals showed negative reactions to white petrolatum. <i>Conclusion:</i> Our previous data and results of this study give positive proof that both IgE-mediated immediate allergy and cell-mediated delayed hypersensitivity to a mite antigen contribute to the development of skin eruptions on NC/F mice resembling human atopic dermatitis.
Effect of a Prostacyclin Analogue, Iloprost, on Urinary Aquaporin-2 Excretion in Humans
Authors: Buemi Michele , Di Pasquale Giuseppe , Ruello Antonella , Floccari Fulvio , Aloisi Carmela , Latassa Giuseppe , Corsonello Andrea , Sturiale Alessio , Corica Francesco , Frisina Nicola 
Published: April 2003

The regulation of aquaporin-2 (AQP2) water channel excretion in the collecting duct depends mainly on the action of vasopressin (AVP). Recently, however, other regulatory factors have been identified: atrial natriuretic factor, oxytocin and prostaglandins. In healthy volunteers (5 males, 5 females; mean age 23 ± 3 years) we therefore evaluated the effect of a stable analogue of prostacyclin-2 (PGI<sub>2</sub>), iloprost, on renal function and on the urinary excretion of AQP2 (U-AQP2). After 6 h of iloprost infusion, U-AQP2 increased from 0.8 ± 0.15 to 1.8 ± 0.2 pmol/mg creatinine (p < 0.001), while the urinary flow rate increased from 1.4 ± 0.2 to 1.8 ± 4 (p < 0.01). No significant change was found in the AVP serum concentration, with a basal value of 3.17 ± 0.12 vs. 3.15 ± 0.12 pg/ml after 6 h of prostacyclin infusion. All the values returned to pre-study levels after a recovery period of 6 h. In conclusion, the PGI<sub>2</sub> analogue, iloprost, can induce U-AQP2 excretion independent of AVP.
Red Cell Mass, Spleen Size and Plasma Erythropoietin in Polycythaemia vera and Apparent Polycythaemia
Authors: Johansson Peter , Safai-Kutti Soodabeh , Lindstedt Göran , Suurküla Madis , Kutti Jack 
Published: April 2003

Most frequently, an elevated packed cell volume (PCV) value arouses the suspicion of a polycythaemic state. The aim of the present work was to assess a few readily available variables which could help the clinician to differentiate between polycythaemia vera (PV) and apparent polycythaemia (AP). During a 5-year period, 31 consecutive newly diagnosed patients with PV were identified, and during a 4-year period 38 consecutive subjects were considered to be afflicted with AP. In each subject: (i) the red cell mass (RCM) and plasma volume were measured, (ii) the spleen size was assessed using γ-camera imaging, and (iii) the plasma erythropoietin (EPO) concentration was determined. The diagnosis of PV was based upon recently proposed criteria. By definition, all PV patients had absolute erythrocytosis, i.e. the RCM was greater than 25% above the mean normal predicted value for the individual. There was no statistical difference between the plasma volumes for PV and AP patients. However, the mean measured/predicted plasma volume for subjects with AP was significantly lower than the mean for PV. The means for spleen scan areas (posterior and left lateral projections) for AP patients were identical to the mean reference values for our laboratory. As compared to AP, in PV the spleen scan areas were significantly increased, and the lateral spleen scan area was significantly larger than the posterior area. It was also shown that, in contrast to AP, both spleen scan areas were significantly larger in male than in female PV patients. All PV patients had plasma EPO concentrations below the lower reference limit, and in 68% of the patients undetectable EPO concentrations were present. Most AP patients (84%) had EPO values within the reference range; 8% had slightly subnormal, but not undetectable, plasma EPO levels.
Impact of Cortisol on Emotions under Stress and Nonstress Conditions: A Pharmacopsychological Approach
Authors: Reuter M. 
Published: April 2003

Although the importance of the hypothalamic-pituitary-adrenal axis in emotional stress response is a well-established fact, the causal relationship between glucocorticoids and emotions remains unclear. Therefore, it was tried to elucidate this relationship by an experimental approach in 100 healthy volunteers. The effects of different oral dosages of cortisol (hydrocortisone; 20 and 40 mg) or placebo on emotional states were tested under stress and nonstress conditions in an independent group design. Furthermore, the time of drug application was varied in relation to the onset of the stress/nonstress conditions (1 vs. 2 h prior to exposure). Stress and nonstress conditions were induced by a film depicting violence and neutral scenes, respectively. The results indicate that the application of cortisol ameliorates emotional states irrespective of the time of drug administration and stress exposure. Also the dimensions of activity were increased by cortisol in all experimental conditions, except when applied 1 h before stress onset, indicating an adaptive negative feedback regulation preventing stress-induced overactivation.
Progesterone Inhibits Rejection of Xenogeneic Transplants in the Sheep Uterus
Authors: Majewski A.C. , Hansen P.J. 
Published: April 2003

<i>Objectives:</i> One of the proposed roles of progesterone is to prevent maternal immunological destruction of the allogeneic conceptus. Here, it was demonstrated that progesterone allows survival of a xenotransplant placed in the uterine lumen. <i>Methods:</i> Ovariectomized ewes, surgically prepared to have ligatures around each uterine horn, were given daily subcutaneous injections of 50 mg progesterone or vehicle (sesame oil). After 30 days of treatment, mouse hybridoma cells were transplanted to one ligated uterine horn and phosphate-buffered saline was injected into the other horn. The uterus was flushed after an additional 14 days of treatment and hybridoma cells were identified by immunofluorescence. <i>Results:</i> Overall, hybridoma cells were recovered from 4 of 5 progesterone-treated ewes and 1 of 5 vehicle-treated ewes. Immunohistochemical analysis of intercaruncular endometrium using antibodies towards CD8, γδ, and CD45R lymphocyte markers revealed that local presence of hybridoma cells caused a significant increase in CD8+ cells in all tissue compartments. While not significant, the numbers of CD8+ cells in the luminal and glandular epithelium were lower for progesterone-treated ewes. Progesterone tended to increase γδ T cell numbers in the glandular epithelium. <i>Conclusions:</i> Results demonstrate that xenograft rejection in the uterus is associated with an increase in CD8+ cells in the endometrium and that progesterone can inhibit uterine tissue graft rejection responses sufficiently to allow survival or delay rejection of xenograft tissue.