bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Anatomy of a Clinical Trial
Authors: Shepherd J. , Gaw A. 
Published: April 2003

<i>Objective: </i>Treatment of hyperlipidemia to reduce the risk of ischemic heart disease was, prior to the statin era, disappointingly limited in its ability to yield the benefits expected from the strong relationship known to exist between serum cholesterol and coronary death. Three primary prevention trials, using clofibrate, cholestyramine and gemfibrozil, had achieved modest reductions in fatal and nonfatal coronary events but none was able to extend life overall or even to reduce cardiovascular mortality; and combined analyses of the three raised disquiet over potential links between cholesterol reduction, cancer and aggressive or violent behaviour. The time was therefore ripe to determine whether statins could help prevent that first and all important myocardial infarction. <i>Methods:</i> The West of Scotland Coronary Prevention Study recruited 6,595 45- to 64-year-old men with no history of prior myocardial infarction and with low-density lipoprotein cholesterol in the range 4–6 mmol/l (155–232 mg/dl). Subjects who had undergone coronary revascularisation or had been hospitalised for angina pectoris in the previous 12 months were excluded, as were those with significant electrocardiographic abnormalities. Participants were randomised to receive pravastatin 40 mg/day or matching placebo and were followed for an average of 4.9 years. <i>Results:</i> Treatment with pravastatin reduced the combined risk of fatal and nonfatal myocardial infarction by 31%. Cardiovascular death overall fell by 32% and the need for coronary revascularisation procedures was reduced by 37%. All of these endpoint benefits were statistically significant. Because there was no increase in non-cardiovascular mortality, the reduction in death from any cause also proved to be statistically significant (p = 0.051 by log rank test and p = 0.037 after adjustment for baseline risk factors). <i>Conclusions:</i> The West of Scotland Coronary Prevention Study is the first to show that cholesterol reduction with pravastatin helps avoid the first myocardial infarction, reduces coronary mortality and extends life. Ongoing exploration of the study database continues to unearth additional surprisingly beneficial effects of the treatment and permits authoritative decision-making on the effective use of lipid-lowering drugs.
Comparison of the Protective Effect of Formoterol and of Salmeterol against Exercise-Induced Bronchospasm when Given Immediately before a Cycloergometric Test
Authors: Ferrari Marcello , Segattini Carlo , Zanon Roberto , Bertaiola Mariano , Balestreri Filippo , Brotto Emanuele , Lo Cascio Vincenzo 
Published: April 2003

<i>Background:</i> Salmeterol and formoterol, two long-acting β<sub>2</sub>-adrenergic agonists, have been shown to be effective against exercise-induced bronchospasm (EIB) several hours after inhalation, but no study has yet compared their protective effect immediately after administration. <i>Objectives:</i> To compare the protective effect of inhaled formoterol and salmeterol against EIB immediately and 4 h after administration. <i>Methods:</i> Double-blind, two-period cross-over study of 11 EIB-positive asthmatic subjects (mean age 21.2 years) administered formoterol 24 µg and salmeterol 50 µg by means of metered-dose inhalers (MDIs) on 2 days separated by an interval of 72 h; the subjects performed two cycloergometric exercise tests immediately and 4 h after dosing. Forced expiratory volume (FEV<sub>1</sub>) measurements were made before and at the end of exercise, and then after 3, 5, 10, 15, 20, 25 and 30 min. The maximum percentage decrease in FEV<sub>1</sub> in the 30 min following exercise was considered. <i>Results:</i> Immediately after drug administration, but not 4 h later, formoterol provided significantly better protection against EIB than salmeterol (p = 0.02). The number of formoterol-treated subjects protected against EIB (i.e. with a <15% decrease in FEV<sub>1</sub> after treatment) was 10/11 after the first exercise test and 7/8 after the second; the corresponding figures after salmeterol treatment were 5/11 and 7/8. <i>Conclusions:</i> Our results show that formoterol inhaled via an MDI is effective in preventing EIB as early as within a few minutes of administration, whereas salmeterol does not offer any appreciable protection. On the contrary, the protective effect of the two drugs is clinically equivalent 4 h after administration.
Participation of the 26S Proteasome in the Regulation of Progesterone Receptor Concentrations in the Rat Brain
Authors: Camacho-Arroyo Ignacio , Villamar-Cruz Olga , González-Arenas Aliesha , Guerra-Araiza Christian 
Published: April 2003

The aim of this study was to investigate the participation of the 26S proteasome in the regulation of progesterone receptor (PR) concentrations in the rat brain in vivo. Ovariectomized adult female rats were treated with estradiol (10 µg/100 g s.c.), estradiol + progesterone (400 µg/100 g), and vehicle (corn oil/10% ethanol) in the presence or absence of the proteasome inhibitor Z-Ile-Glu (OBu<sup>1</sup>)-Ala-Leu-H (PSI, 300 µg/100 g). Proteins were extracted from the preoptic area, the hippocampus, and the frontal cortex, and processed for Western blot. Estradiol-induced PR expression in the preoptic area and the hippocampus, whereas progesterone did not modify the effect of estradiol. Neither estradiol nor progesterone modified PR content in the frontal cortex. PSI treatment increased PR content in the preoptic area and the hippocampus. This increase was significant in both regions after 24 h of the treatment with progesterone + PSI in the animals primed with estradiol. In this case, the content of both PR isoforms (PR-A and PR-B) was increased in a similar manner by PSI in the preoptic area (90 and 97%) and in the hippocampus (49 and 50%). PSI did not affect PR content in the frontal cortex. Our results suggest that the 26S proteasome could participate in the turnover of PR in the preoptic area and the hippocampus of the rat in vivo.
Association between the G Protein β3 Subunit 825t Allele and Radial Artery Hypertrophy
Authors: Hanon Olivier , Luong Vu , Mourad Jean Jacques , Bortolotto Luiz A. , Safar Michel , Girerd Xavier 
Published: April 2003

The GNB3 C825T gene polymorphism has recently been identified and associated with hypertension, obesity and left ventricular hypertrophy. The aim of the study was to determine the relationship between the C825T polymorphism of the gene encoding for the G protein β3 subunit (GNB3 C825T) and vascular hypertrophy. We studied a cohort of 306 subjects (age 49 ± 12 years) without evidence of cardiovascular disease and never treated with cardiovascular drugs. Vascular phenotypes were evaluated for the common carotid and radial arteries using high-resolution echo-tracking devices. Genotype frequencies were in agreement with the Hardy-Weinberg equilibrium. For the radial artery, mean wall thickness was significantly higher in subjects carrying the 825T allele than in CC genotype subjects (240 ± 54 µm for CT genotype and 241 ± 53 µm for TT genotype vs. 222 ± 52 µm for CC genotype, p = 0.01). The frequency of the 825T allele was significantly different in subjects with (52%) and without (35%) radial artery hypertrophy (χ<sup>2</sup> = 10.88, p < 0.001). The relative risk of radial artery hypertrophy in subjects carrying the 825T allele compared with those with the CC genotype was 3.02 (95% CI 1.53– 5.95). A logistic regression analysis indicated that the positive and significant association between the 825T allele and radial artery hypertrophy was independent of age, blood pressure, gender and BMI. In contrast, no association between genotypes and carotid artery wall thickening was observed. These results suggest that some genetic characteristics determine in part the patterns of radial artery geometrical changes. As the 825T allele is associated with vascular hypertrophy of a muscular artery but not with structural changes of an elastic artery, we hypothesize that the 825T allele may be a genetic marker of arteriolosclerosis.
Results of Hepatitis B Vaccination in Sarcoidosis
Authors: Mert Ali , Bilir Muammer , Ozaras Resat , Tabak Fehmi , Karayel Tuncer , Senturk Hakan 
Published: April 2003

<i>Background: </i>Sarcoidosis is known to be associated with defects in cellular immunity, especially in reference to T helper lymphocytes. Anergy to a tuberculin skin test is most characteristic of this disease. <i>Objectives: </i>To further the data on impaired immunity, we studied the antibody response to hepatitis B vaccination in patients with sarcoidosis. <i>Methods: </i>Serologic markers of hepatitis B virus (HBV) (HBsAg, anti-HBs, anti-HBc) were studied in 40 patients with sarcoidosis (32 female, 8 male; mean age: 45 ± 11 years, range: 25–66 years) with a mean duration of disease of 6 years. While all the markers were negative in 22 patients (55%), 2 had isolated anti-HBc positivity and 16 had both anti-HBc and anti-HBs antibodies. Thirty-five age- and sex-matched healthy subjects were studied as controls. Recombinant HBV vaccines (Genhevac B Pasteur, 20 µg) were administered (at 0 , 1, and 6 months) to 16 of the seronegative cases and the controls and antibody titres were measured 1 month after the last dose. The tuberculin skin test was negative in all cases. <i>Results: </i>While none of the vaccinees in the diseased group responded, the control group yielded an antibody response rate of 85.7% (30/35), with a mean titre of 257.9 mIU/ml. <i>Conclusions: </i>Patients with sarcoidosis were invariably unresponsive to standard vaccination, while some of the diseased subjects had already mounted a natural antibody response, either before or after the development of the original disease. Cellular immunodeficiency in sarcoidosis could be a suitable model for studying immunological interactions between HBV and the host.
Ovariectomy-Induced Increases in Hypothalamic Serotonin-1A Receptor Function in Rats Are Prevented by Estradiol
Authors: Raap Dani K. , DonCarlos Lydia L. , Garcia Francisca , Zhang Yahong , Muma Nancy A. , Battaglia George , van de Kar Louis D. 
Published: April 2003

The present study investigated the effects of long-term estradiol withdrawal (ovariectomy) on hypothalamic serotonin-1A (5-HT<sub>1A</sub>) receptor signaling. Changes in neuroendocrine responses to the 5-HT<sub>1A</sub> agonist 8-OH-DPAT and levels of G<sub>z</sub> protein in the hypothalamus were used to examine 5-HT<sub>1A</sub> receptor signaling. Five days following ovariectomy, rats received daily injections of either 2 µg of β-estradiol 3-benzoate or vehicle (subcutaneously) for 2, 4 or 14 days. Twenty-four hours after the last injection, and 15 min prior to sacrifice, rats were injected with (±)8-OH-DPAT (50 µg/kg, s.c.) or saline. Estradiol treatment did not alter basal corticotropin (ACTH) or oxytocin levels. Injection of (±)8-OH-DPAT produced significant increases in plasma ACTH and oxytocin levels. In the vehicle-treated rats, hormone responses to 8-OH-DPAT were enhanced in rats that received injections for 14 days compared with rats that received injections for either 2 or 4 days. Estradiol treatment for 4 or 14 days blunted this enhanced ACTH response to 8-OH-DPAT, whereas the oxytocin response to 8-OH-DPAT was only blunted after 14 daily injections of β-estradiol 3-benzoate. The treatment with β-estradiol 3-benzoate (2 µg/rat) did not reduce membrane-associated G<sub>z</sub> protein levels in the paraventricular nucleus of the hypothalamus. Hence, the inhibitory influence of a low dose of β-estradiol 3-benzoate on 5-HT<sub>1A</sub> receptor signaling in the hypothalamus is not accompanied by a change in the levels of G<sub>z</sub> protein in the paraventricular hypothalamic nucleus. Results from the present study indicate a supersensitivity of 5-HT<sub>1A</sub> receptors after withdrawal of estradiol and suggest that estradiol suppresses 5-HT<sub>1A</sub> receptor signaling.
Polymorphic Genes for Kinin Receptors, Nephropathy and Blood Pressure in Type 2 Diabetic Patients
Authors: Zychma Marcin J. , Gumprecht Janusz , Trautsolt Wanda , Szydlowska Ilona , Grzeszczak Wladyslaw 
Published: April 2003

<i>Background/Aims:</i> There is evidence that hereditary predisposition contributes to the development of diabetic nephropathy and hypertension. Polymorphisms in the genes for bradykinin receptors (B<sub>1</sub>R and B<sub>2</sub>R) were found to be associated with decreased risk of the development of end-stage renal disease. This study examines whether B<sub>1</sub>R G<sup>–699</sup>C and B<sub>2</sub>R C<sup>181</sup>T polymorphisms are associated with microalbuminuria or overt nephropathy, or blood pressure variation in type 2 diabetic subjects. <i>Methods:</i> B<sub>1</sub>R and B<sub>2</sub>R polymorphisms were determined in 153 type 2 diabetic patients with microalbuminuria, 132 with overt nephropathy (macroalbuminuria or chronic renal failure), and 161 patients with normoalbuminuria despite diabetes duration longer than 10 years. <i>Results: </i>Distributions of the examined polymorphisms did not differ between patients with microalbuminuria or overt nephropathy, compared to normoalbuminuric control subjects. Patients carrying the B<sub>2</sub>R T allele had lower DBP, compared with non-carriers: 83.6 ± 12.0 vs. 87.4 ± 12.1 mm Hg, p < 0.05. Among patients not receiving ACEI, both SBP and DBP was significantly lower in B<sub>2</sub>R T allele carriers, compared to non-carriers (137.2 ± 20.3 vs. 146.5 ± 21.7 mm Hg, and 80.3 ± 11.9 vs. 85.8 ± 11.6 mm Hg, p < 0.05). <i>Conclusions:</i> Examined polymorphisms are not associated with the increased risk of incipient or overt nephropathy in type 2 diabetic patients. B<sub>2</sub>R C<sup>181</sup>T polymorphism may contribute to blood pressure variation in these subjects.
Identification of a Vimentin-Reactive Peptide Associated with Ocular Lens Membranes as Cytokeratin
Authors: Brooks Joseph , Fleschner C.R. 
Published: April 2003

We wished to identify a 44-kD peptide isolated from lens membrane fractions which has apparent immunoreactivity to antivimentin and to antiphakinin. Urea-soluble proteins from rat lens membrane fractions were separated by two-dimensional electrophoresis, transferred to polyvinylidene fluoride membranes and probed with monoclonal antibodies to vimentin or cytokeratins, or a polyclonal antibody to phakinin. The monoclonal antibody to vimentin recognized the expected protein (M<sub>r</sub> = 56 kD, pI = 5.1) and several smaller and more acidic peptides including a 44-kD spot with a pI of 4.9. A similar pattern of immunoreactivity was found with commercially available purified vimentin. The polyclonal antibody to phakinin recognized the expected protein (M<sub>r</sub> = 52 kD, pI = 5.0) and several smaller and more acidic peptides, including a 44-kD spot with a pI of 4.9. Matrix-assisted laser desorption ionization mass spectroscopy analysis of the tryptic digest of the spot corresponding to 44 kD and pI of 4.9 identified neither vimentin nor phakinin but did identify peptides derived from ovalbumin (added to samples as an internal standard) and cytokeratin 1. Antibodies which recognize cytokeratin 1 reacted weakly with a 44-kD peptide which comigrated with the 44-kD vimentin-immunoreactive peptide in adjacent lanes of single-dimension SDS polyacrylamide gels. The 44-kD acidic (pI = 4.9) peptide which reacts with a monoclonal antibody to vimentin may be derived from cytokeratin 1.
A Nitric Oxide-Generating Beta-Blocking Agent Prevents Renal Injury in the Rat Remnant Kidney Model
Authors: Takamitsu Yoshihiro , Nakanishi Takeshi , Nishihara Futoshi , Hasuike Yukiko , Izumi Masaaki , Inoue Toru , Hiraoka Keisuke , Itahana Reiko , Miyagawa Koji 
Published: April 2003

<i>Background:</i> The <i>L-</i>arginine-nitric oxide (NO) pathway plays an important role in the modulation of glomerular disease. We investigated whether β-blocking agents, with and without an NO-generating function, had renoprotective effects in the 5/6 nephrectomized rats (Nx), an animal model of glomerulosclerosis. <i>Methods:</i> Nipradilol, a β-blocker with an ONO<sub>2</sub> group (5, 10 or 15 mg/kg/day) and propranolol, a β-blocker without this group (50 mg/kg/day) were administered for 12 weeks to Nx together with and without nitro-<i>L</i>-arginine methyl ester (L-NAME). We evaluated the effects of both drugs on proteinuria, hypertension, renal function, glomerulosclerosis and urinary excretion of NO metabolites (U<sub>NOx</sub>) and cyclic GMP (U<sub>cGMP</sub>). <i>Results:</i> Both drugs similarly attenuated the elevated blood pressure in Nx. However, nipradilol, at doses of 10 and 15 mg/kg/day, significantly decreased proteinuria and glomerulosclerosis, while propranolol did not. Nx showed reduced U<sub>NOx</sub> in comparison with the sham-operated rats. Nipradilol increased U<sub>NOx</sub> and U<sub>cGMP</sub> significantly and in a dose- dependent manner, whereas propranolol reduced them to levels lower than those in Nx. Nx receiving L-NAME reduced U<sub>NOx</sub>. The addition of nipradilol increased U<sub>NOx</sub> and decreased urinary protein excretion and glomerulosclerosis, suggesting that the NO released from the drug contributed to its renoprotective effect. <i>Conclusion:</i> These findings indicate that nipradilol exerts its renoprotective effect through NO generation, and not by lowering blood pressure. The β-adrenergic blocking action per se does not seem to be related to the renoprotective effect of these agents.
Axial Length Changes Accompanying Successful Nonpenetrating Glaucoma Filtration Surgery
Authors: Üretmen Önder , Ateş Halil , Andaç Kutay , Deli Belgin 
Published: April 2003

We aimed to evaluate the effect of nonpenetrating glaucoma filtration surgery on axial length (AL). Thirty patients (30 eyes) who underwent successful nonpenetrating glaucoma filtration surgery were prospectively analyzed. AL was measured preoperatively and postoperatively at 1 and 12 months. Associations between change in AL and age, gender, diagnosis, preoperative and postoperative visual acuity, refraction and intraocular pressure (IOP) were analyzed. AL decreased in 22 of 30 eyes postoperatively. The mean change in AL measurement was –0.15 ± 0.27 mm (range –1.37 to +0.12 mm) at 1 month. Regression analysis showed that young age, a high preoperative IOP and a greater change in IOP were associated with a greater decrease in AL (p < 0.02). The mean AL at 12 months was almost the same as the preoperative value (p >0.2), but was significantly greater than the mean AL 1 month postoperatively (p = 0.001). There was no statistically significant difference between the IOP levels obtained postoperatively at 1 and 12 months (p >0.1). Nonpenetrating glaucoma surgery can result in a small decrease in AL which can reverse during the follow-up period.
The Middle Cerebral Artery Flow Velocities during Head-Up Tilt Testing in Diabetic Patients with Autonomic Nervous System Dysfunction
Authors: Žvan Bojana , Zaletel Marjan , Pretnar Oblak Janja , Pogačnik Tomaž , Kiauta Tomaž 
Published: April 2003

<i>Background:</i> The goal of this study was to examine the effects of diabetes mellitus on the trend of mean arterial velocity (v<sub>m</sub>) in both middle cerebral arteries during head-up tilt (HUT). <i>Methods:</i> The study was performed in 20 patients, 9 females and 11 males (mean age 51 ± 12 years) with an average 17-year history of insulin-dependent diabetes mellitus type I or II and a dysfunction of the autonomic nervous system confirmed by cardiocirculatory tests [Valsalva maneuver, deep breathing test, handgrip test, orthostatic test and spectral analysis of heart rate (HR) variability], and 19 age-matched healthy volunteers, 9 females and 10 males (mean age 48 ± 6.8 years). v<sub>m</sub> was measured by a transcranial Doppler monitoring system during a 5-min baseline period, followed by a 5-min HUT in the upright position (90°). Mean arterial blood pressure (MAP), HR and end-tidal CO<sub>2</sub> (Et-CO<sub>2</sub>) were monitored concomitantly. <i>Results:</i> In healthy volunteers, v<sub>m</sub> decreased stepwise during the first minute of HUT, reaching a minimum during the last 2 min of the test (v<sub>m</sub>: basal 63.0 ± 11.7 cm/s, 1st min 57.6 ± 12.2 cm/s, 2nd min 55.9 ± 12.6 cm/s, 3rd min 53.4 ± 12.6 cm/s, 4th min 52.1 ± 12.7 cm/s, 5th min 51.3 ± 13.5 cm/s). In the supine position, v<sub>m</sub> recovered and reached the resting v<sub>m</sub> values. It declined gradually during HUT and less steeply in diabetic (v<sub>m</sub>: basal 54.4 ± 10.1 cm/s, 1st min 51.96 ± 9.3 cm/s, 2nd min 50.7 ± 11.6 cm/s, 3rd min 50.5 ± 11.4 cm/s, 4th min 49.5 ± 10.7 cm/s, 5th min 48.8 ± 11.5 cm/s) than in healthy subjects. v<sub>m</sub> differed significantly (p = 0.00) between rest and HUT in both groups. The differences in MAP, HR and Et-CO<sub>2</sub> during rest and HUT between the groups were not statistically significant (p ΔMAP = 0.36, p ΔHR = 0.86, p ΔEt-CO<sub>2</sub> = 0.97). The results of the analysis of variance of v<sub>m</sub> for repeated measurements between the two groups of subjects were highly significant (p = 0.00). The model of linear regression analysis was significant (p = 0.007). Diabetes was significant in the model (p = 0.00), while ΔMAP, ΔHR and ΔEt-CO<sub>2</sub> were not. <i>Conclusions:</i> These findings may indicate that vasomotor responses during HUT testing are decreased in diabetic patients.
Ischemic Preconditioning of Renal Tissue: Identification of Early Up-Regulated Genes
Authors: Damario Gomes Marcelo , Vasconcelos Cancherini Douglas , Amaral Rebouças Moreira Marise , Amaral Rebouças Nancy 
Published: April 2003

Given the important effects of ischemic preconditioning (IPC) in minimizing tissue damage induced by sustained ischemia in several tissues, this study evaluated the effect of IPC in preserving renal function and identified up-regulated genes after 30 min of preconditioning. IPC induced by 2, 3 and 4 min of ischemia, intercalated by 5 min of reperfusion, induced a measurable protection of renal function and morphology. The improved functional and histological parameters occurred in parallel with up-regulation of 39 genes, as evaluated by subtractive hybridization; for 13 of them we could show, by RNAse protection assay, a significant increase in mRNA levels. These genes code for chaperones/chaperonins and cytoskeleton proteins that could be involved in preservation of protein folding and cellular structures after sustained ischemia; proteins related to oxidative metabolism that might be relevant for cellular use of alternate sources of energy or for faster recovery of ATP levels in this condition, and proteins that are putative scavengers of oxidant products. Summarizing, ischemic preconditioning induced up-regulation of genes that code proteins whose functional roles suggest their involvement in the tolerance of the preconditioned tissue to sustained ischemia.