bluuebunny/crossref_metadata_2025 huggingface dataset:
The Prognostic Role of Brain Natriuretic Peptides in Hemodialysis Patients
Authors: Naganuma Toshihide , Sugimura Kazunobu , Wada Seiji , Yasumoto Ryoji , Sugimura Takeshi , Masuda Chikayoshi , Uchida Junji , Nakatani Tatuya
Published: April 2003

Background: Although plasma concentrations of brain natriuretic peptides (BNP) increase in hemodialysis (HD) patients as well as patients with cardiovascular diseases (CD), the clinical significance of BNP in HD patients has yet to be elucidated. In this study, we investigated the pathophysiological significance of BNP in HD patients. Methods: Plasma BNP concentrations were measured in 164 HD patients after HD and 14 healthy volunteers. In 12 patients without CD, BNP was also measured before HD. Multiple regression analysis was performed to determine the important factors causing increased plasma BNP concentrations. Cardiac mortality was monitored for 36 months after baseline analysis, and the prognostic role of BNP was examined by Cox proportional hazards regression analysis. Results: Plasma BNP concentrations of HD patients without CD decreased significantly during HD session (124.5 ± 90.7 vs. 91.4 ± 67.6 pg/ml, mean ± SD, p = 0.004), but were still significantly higher than those of the healthy subjects (9.7 ± 9.2 pg/ml, p = 0.0002). Plasma BNP concentrations of patients with CD were significantly higher than of those without CD (579.6 ± 564.3 vs. 204.0 ± 241.5 pg/ml, p < 0.0001). Plasma BNP concentrations were also significantly higher in diabetes mellitus (DM) patients than in non-DM patients (514.1 ± 585.4 vs. 296.0 ± 347.0 pg/ml, p = 0.0031). Multiple regression analysis showed that left ventricular mass index (LVMI), CD and DM were independent factors for the elevated BNP (R2 = 0.303, p < 0.0001). During a 36-month follow-up period, cardiac death occurred in 13 patients. Kaplan-Meier survival estimates of patients from varying plasma BNP quartiles (<200, 200–450, 450–700 and >700 pg/ml) differed between the four groups (p < 0.0001). The group with the highest BNP level (>700 pg/ml) had the lowest survival. When compared with patients with BNP <200, the hazard ratios for cardiac death of patients with BNP of 200–450, 450–700 and >700 pg/ml were 2.3 [95% confidence interval (CI) 0.14–36.7], 18.7 (1.9–183.4) and 51.9 (6.5–416.3), respectively. The univariate Cox proportional hazards model showed that BNP, left ventricular ejection fraction, LVMI, age, DM, serum albumin and C-reactive protein (CRP) were significantly associated with the risk of cardiac mortality. By stepwise multivariate Cox proportional hazards analysis, only BNP, LVMI and CRP remained powerful independent predictors of cardiac death. The relative risk ratios were 1.002 (95% CI 1.001–1.002) for BNP, 2.192 (1.532–3.135) for CRP and 1.027 (1.013–1.042) for LVMI. Conclusion: High plasma BNP concentrations in HD patients were associated with volume overload, left ventricular hypertrophy, CD and DM. Plasma BNP concentration may be a useful parameter for assessing the risk of cardiac death in HD patients by providing prognostic information independently of other variables previously reported.
Idiopathic IgA Nephropathy with Diffuse Crescent Formation
Authors: Tang Zheng , Wu Yan , Wang Qing-wen , Yu Yu-sheng , Hu Wei-xing , Yao Xiao-dan , Chen Hui-ping , Liu Zhi-hong , Li Lei-shi
Published: April 2003

Objective: To investigate the clinicopathological features and outcome of idiopathic IgA nephropathy with diffuse crescent formation in Chinese patients. Methods: Twenty-five patients with diffuse crescentic IgA nephropathy (DCIgAN), 15 males and 10 females with median age of 28.5, and median disease duration of 5.1 months, were studied. Their clinical, laboratory and pathological features and outcome were investigated. Twenty-one were administered pulse immunosuppressive therapy, and 15 were followed up for more than 6 months. Results: 1.14% had total IgA nephropathy, and 16.4% total diffuse crescentic glomerulonephritis. Clinically, most of patients (88%) showed rapidly progressive glomerulonephritis associated with a high level of serum creatinine (418 ± 264 µmol/l). Gross hematuria was noted in 72%, hypertension in 64%, and nephrotic syndrome in 48%. Pathologically, except for diffuse crescent formation (a median 65% and range 50–95%), we observed segmental necrosis of glomerular capillaries in 60%, glomerular infiltrating cells in 48%, endothelial cells proliferation in 32%, and rupture of Bowmans’ capsule in 24%. Severe tubular interstitial damage was also found, tubular atrophy in 64%, interstitial fibrosis in 60%, diffuse interstitial infiltrating cells in 74%, and interstitial vasculitis in 40%. Immunopathologically, four phenotypes were observed; however, IgA associated with IgM deposition was higher than that in patients with general IgA nephropathy (IgAN). In addition, the infiltrating CD4+, CD8+, CD68+ and PCNA+ cells in renal tissue were significantly high compared with that in controls. In a follow-up study, 66.7% of patients had life-sustaining renal function, 4 of them had normal range of serum creatinine (<124 µmol/l), and only 5 were dialysis-dependent. Conclusions: The patients with crescentic IgA nephropathy mostly show rapidly progressive nephritis associated with more severe pathological changes including glomerular, tubular interstitial and vascular lesions than in patients with general IgAN. The infiltrates in glomeruli may contribute to the crescentic formation, and the intensive immune suppressing treatment is useful to improve renal damage in patients with DCIgAN.
Pathogenesis and Treatment of Hypernatremia
Authors: Kang Sung-Kyew , Kim Won , Oh Man S.
Published: April 2003

Two aspects of hypernatremia are emphasized in this discussion: pathogenesis and treatment. Hypernatremia rarely develops with increased water loss alone; there must be a mechanism that interferes with water intake. In treating hypernatremia, the speed of correction is important because the volume regulation mechanisms restore the brain volume to normal when hypernatremia is chronic. Thus, too rapid correction of chronic hypernatremia results in brain edema. The calculation of fluid volume needed to correct hypernatremia can be obtained with use of various formulae described here for the fluid that contains dextrose in water or for hypotonic saline solution. Accurate prediction of the fluid volume requirement demands the knowledge of urine output and its electrolyte content, but when the information is not available, urine may be assumed to be isotonic in its electrolyte content.
Bartter’s, Gitelman’s, and Gordon’s Syndromes
Authors: Kamel Kamel S. , Oh Man S. , Halperin Mitchell L.
Published: April 2003

The molecular basis of many of the inherited disorders of potassium homeostasis has become much clearer in the last two decades. Despite these new insights into the physiology of renal potassium handling, a number of questions remain to be answered. The examples we use to illustrate these issues are Gordon’s syndrome, Bartter’s syndrome, and Gitelman’s syndrome. Our objective is to integrate these new insights into an understanding of the pathophysiology of renal potassium handling. We also propose different ways to think about some of the unresolved issues in this area.
Modulation of Age-Related Biochemical Changes and Oxidative Stress by Vitamin C and Glutathione Supplementation in Old Rats
Authors: Amer M.A.
Published: April 2003

The present study sought to determine whether supplementation of dietary antioxidant ascorbic acid with glutathione (GSH) could ameliorate the age-related increased oxidative stress and changes in hormonal, lipid and copper (Cu) as well as zinc (Zn) levels in 18-month-old rats. The present study demonstrated that supplementation of vitamin C (30 mg) + GSH 100 mg/kg b.w. significantly reduced the concentration of thiobarbituric acid-reactive substances in liver and testes in old male rats as compared with nonsupplemented ones, indicating lower oxidative stress. In addition, testicular GSH was increased but not hepatic GSH. Also, cholesterol and triglycerides were decreased in the serum of supplemented rats. Furthermore, she serum testosterone level was increased in the same supplemented rats. However, the present results show that the thyroid hormones, T3 and T4, were not influenced. Lastly, the concentration of Cu in serum, liver, brain and testes was increased in supplemented old rats. Zn concentration was also increased in the same organs but not in the liver. According to the present study, the supplementation of antioxidants could play an important role in the modulation of the oxidative damage and changes associated with age.
An Assessment of Docosahexaenoic Acid Intake from the Viewpoint of Safety and Physiological Efficacy in Matured Rats
Authors: Saito Morio , Kubo Kazuhiro
Published: April 2003

Background/Aims: In order to clarify an appropriate intake of docosahexaenoic acid (DHA, 22:6n–3), from the viewpoint of safety and physiological efficacy, the potential changes in lipid peroxidation and antioxidant defense in serum and tissues as well as those in serum lipid levels were examined in matured rats at the age of 1 year. Methods: Rats were given the diets containing graded levels of purified DHA (0, 1.0, 3.1 and 8.4% of total energy, en%) for 30 days (control and 1.0, 3.1 and 8.4 en% groups). Lipid peroxides and α-tocopherol levels in serum and tissues, and lipid levels in serum were measured. Results: Serum α-tocopherol concentrations in the 3.1 and 8.4 en% groups were significantly lower than those in the control group. Liver lipid peroxide levels assessed using the microsomal conjugated dienes were significantly higher in the 3.1 and 8.4 en% groups than those in the control group, and the chemiluminescence intensity and thiobarbituric acid value were significantly greater in the 8.4 en% group than in the control group. The liver α-tocopherol level decreased in response to the increases in lipid peroxide levels, but a significant difference was recognized only in the 8.4 en% group. In the kidney, no changes in lipid peroxide levels were observed, but the α-tocopherol level was significantly lower in the 8.4 en% group than in the control group. The levels of all the serum lipids including total cholesterol, HDL-cholesterol, triacylglycerols and phospholipids decreased as the dietary DHA level increased, and total cholesterol and phospholipid concentrations were significantly lower in the 3.1 and 8.4 en% groups than in the control group. Conclusion: These experimental results suggest that the dietary intake of DHA should not be more than 3 en% in matured rats to avoid the potentially chronic deleterious influences caused by lipid peroxidation in serum and tissues, and that the amelioration of serum lipid levels is recognized in rats fed DHA at 3 en% and above.
Relationship between Measures of Fatness, Lipids and Ethnicity in a Cohort of Adolescent Boys
Authors: Mehta Sangeeta , Mahajan Deepika , Steinbeck Katherine S. , Bermingham Margaret A.
Published: April 2003

Background/Aim: The investigators were invited into a boys’ high school to assess the lipid risk profile of a single year cohort and advise on how the findings could be incorporated into a healthy lifestyle program. The aim of the study was to investigate the relationship between measures of fatness, ethnicity and cardiac risk factors in a cohort of adolescent boys. Methods: Anthropometric measurements of weight, height, waist and hips were used to calculate body mass index (BMI) and waist to hip ratio (WHR); percent total body fat (%TBF) was estimated by bioelectric impedance analysis. Demographic and behavioral variables were assessed by questionnaire. Total cholesterol (TC), high-density lipoprotein-cholesterol (HDL-C), triglyceride (TG), apolipoprotein A1 (apoA1), apoliproprotein B (apoB) and insulin were measured in 137 subjects; low-density lipoprotein (LDL-C) was calculated. Results: The study sample was comprised of 139 boys aged 15.7 ± 0.04 years; 46% were Caucasians, 41% were East Asians and 13% were from the Indian subcontinent (South Asian). The crude mean BMI, %TBF and waist measurements were not significantly different between the ethnic groups. South Asians had a higher mean WHR than East Asians (p < 0.004; ANOVA), and also had higher mean %TBF than Caucasians when BMI was adjusted for, and lower BMI than either of the other groups when adjusted for waist (ANCOVA). There was no difference between groups in lipid profiles except for a higher apoB in East Asians compared with Caucasians (p < 0.04). Twenty-two percent of the subjects had TC higher than the desirable level for children (4.5 mmol/l), 7.3% had low HDL-C (<0.9 mmol/l) and 4.3% had high LDL-C (>3.5 mmol/l). Overweight and hypercholesterolemia had individual prevalences of around 20%, while hyperinsulinemia was 48%. Conclusion: The present study confirms that the relationship between BMI and %TBF is dependent on ethnicity, even in adolescent subjects of similar age and gender. The assessment of cardiovascular risk on a school year and age basis would suggest that there are enough affected individuals to support at least a nontargeted intervention which focuses on healthy eating and physical activity.
Effect of L-Carnitine on Weight Loss and Body Composition of Rats Fed a Hypocaloric Diet
Authors: Brandsch Corinna , Eder Klaus
Published: April 2003

Background/Aims: Several studies have been published in recent years which suggest that L-carnitine supplementation can influence the lipid metabolism in some species and can also affect body composition of growing animals. Only few results are available so far on the effect of L-carnitine supplementation on weight reduction and body composition of animals fed an energy-deficient diet. The aim of this study was therefore to investigate whether L-carnitine supplementation combined with an energy-deficient diet can influence weight development and body composition. Methods: An experiment was conducted with 36 rats with an initial body weight of about 460 g. One-third of the rats were killed, the remainder were divided into two groups (control group, treated group) and fed a semi synthetic diet at an energy level of about half of the rats’ maintenance requirement. The basal diet was essentially carnitine-free. The diet of the treated group was supplemented with L-carnitine (5 g/kg). The feeding period extended over 23 days. Experimental parameters were weight loss, composition of carcass and weights of the fat pads surrounding the kidneys, intestine and testes; several clinico-chemical plasma parameters were also determined. Results: As was to be expected, the rats lost a considerable amount of weight on the energy-reduced diet. At the same time a shift occurred in the ratio of fat to protein in favour of protein in the carcass, leading to a marked reduction of body fat levels and a slight reduction of protein levels. There were, however, no significant differences between the control group and the treated group (with L-carnitine supplementation) with regard to any of these parameters. The clinico-chemical parameters measured in plasma (glucose, triglycerides, total cholesterol, free fatty acids, 3-hydroxybutyric acid) also showed no differences between the groups. Conclusions: The rat model used here did not show a positive effect of L-carnitine supplementation on weight loss and body composition of rats fed an energy-deficient diet. The animals’ endogenous carnitine synthesis was obviously adequate to ensure efficient β-oxidation of fatty acids during the catabolic phase.
Dose-Response Effect of Egg-Phosphatidylcholine on Maze-Learning Ability and Fatty Acid Composition of Plasma and Brain in Aged Mice Fed an n–3 Fatty Acid-Deficient Diet
Authors: Lim Sun-Young , Suzuki Hiramitsu
Published: April 2003

Background/Aims: We investigated the dose-response effect of egg-phosphatidylcholine (PC) on the maze-learning ability and brain fatty acid composition in aged mice. Method: Male Crj:CD-1 mice aged 18 months were fed the following diets for 4 months: (i) 5 g palm oil/100 g diet (n–3-deficient control group); (ii) 1 g egg-PC/100 g diet plus 4 g palm oil/100 g diet (egg-PC 1% group); (iii) 2.5 g egg-PC/100 g diet plus 2.5 g palm oil/100 g diet (egg-PC 2.5% group), and (iv) 5 g egg-PC/100 g diet (egg-PC 5% group). Maze-learning ability was assessed 3 months after the start of the experiment. All animals were maintained on the n–3 fatty acid-deficient diets to examine the direct effect of egg-PC on maze behavior. The time required to reach the maze exit and the number of times that a mouse strayed into blind alleys in the maze were measured in 3 trials every 4 days. Results: Our results showed that the 2.5 and 5% egg-PC groups needed less (p < 0.05) time to find the exit and strayed into blind alleys fewer times (p < 0.05) than the control group. In order to determine the relationship between maze-behavior and brain docosahexaenoic acid (DHA) and arachidonic acid (AA) levels in aged mice fed various doses of egg-PC, the plasma and brain fatty acid composition was examined. Dose-response increases in the percentage of DHA were found in plasma lipids. However, based on our data on the brain fatty acid composition of mice fed various doses of egg-PC, no significant differences in the percentages of DHA and AA among the dietary groups were observed. Conclusion: These results suggest that the intake of egg-PC improves maze-learning ability in aged mice fed n–3 fatty acid-deficient diets but it does not influence the percentage of brain DHA and AA.
Cyclosporine or FK506 Decrease Mature Epidermal Growth Factor Protein Expression and Renal Tubular Regeneration in Rat Kidneys with Ischemia/Reperfusion Injury
Authors: Yang Chul Woo , Lee Seung Hun , Lim Sun Woo , Jung Ju Young , Kim Wan Young , Kim Hyung Wook , Choi Bum Soon , Li Can , Cha Jung Ho , Kim Yong Soo , Kim Jin , Bang Byung Kee
Published: April 2003

Background: Epidermal growth factor (EGF) plays an important role in tubular regeneration in kidneys with ischemia/reperfusion (I/R) injury. This study was undertaken to evaluate the influence of cyclosporine A (CsA) or FK506 on mature EGF expression and tubular regeneration in rat kidneys with I/R injury. Methods: Two separate studies were performed. First, the expression of EGF and tubular regeneration was observed in rat kidneys with I/R injury on days 1, 2, 3, 5, and 7. Second, the dose-dependent response of EGF expression and tubular regeneration to CsA (5, 10, and 20 mg/kg) or FK506 (0.25, 0.5, and 1.0 mg/kg) was observed in rat kidneys with I/R injury. I/R injury was induced by clamping both renal arteries for 45 min, and CsA or FK506 was injected just after release of vascular clamps. Rats were sacrificed on day 1 for evaluation of EGF expression, and on day 2 for evaluation of BudU-positive cells. Renal function, tubular injury score, EGF expression assessed by immunoblotting, levels of CsA and FK506 in whole blood, and immunostaining for BrdU was studied. Results: EGF expression was maximal on day 1 (cortex, 29-fold; medulla, 31-fold compared with sham-operated controls), and renal tubular regeneration measured with the number of BrdU-positive cells was maximal on days 2 and 3 in kidney with I/R injury, and thereafter the level of EGF and the number of BrdU-positive cells decreased progressively. CsA or FK506 treatment to ischemic rat kidneys reduced the expression of EGF and the number of BrdU-positive cells in a dose-dependent manner. Conclusions: CsA or FK506 treatment delays recovery from acute tubular necrosis, and this may be associated with decreased EGF expression by CsA or FK506.
AQP1 in Red Blood Cells of Uremic Patients during Hemodialytic Treatment
Authors: Buemi M. , Floccari F. , Di Pasquale G. , Cutroneo G. , Sturiale A. , Aloisi C. , Ruello A. , Romeo A. , Favaloro A. , Corica F. , Frisina N. , Anastasi G.
Published: April 2003

Hemodialysis influences the transport of water through the erythrocytic membrane, and induces morphologic and functional modifications. Recently water channels, called aquaporins (AQP), have been identified on the membrane of red blood cells. The aim of the present study was, therefore, to evaluate any relationships between volumetric changes in erythrocytes (MCV), plasma osmolarity and membrane expression of AQP1 in 22 uremic patients during a hemodialysis session, and compare value with those in a control group of 22 healthy volunteers. Membranal AQP1 expression was evaluated using three methods: indirect immunofluorescence under confocal microscopy, immunoenzymatic method after membrane extraction, and immunoblotting. In uremic subjects, at baseline membrane AQP1 expression was significantly lower, whereas plasma osmolality was higher than in controls. At 1 and 2 h of replacement therapy, a progressive increase was observed in erythrocytic AQP1, values similar to those in controls being attained after 3.5 h. During the session osmolality values reduced progressively, becoming significantly lower than basal values. The mean erythrocytic corpuscular volume in patients with ESRD was significantly lower than in cntrols at baseline. This value increased during hemodialysis, attaining statistical significance with respect to the basal value at 3.5 h of dialysis. Close correlations were found between plasma osmolality and AQP1 values (r = –0.930; p < 0.05), and also between MCV and plasma osmolality trend (r = –0.909; p < 0.05). There was a linear correlation (r = 0.63, p < 0.05) between plasma AVP concentrations and plasma osmolality. The variations found in plasma osmolarity during hemodialysis, may induce AQP1 expression on the membrane of intact red blood cells.
Prediction of Relapse by Plasma Lipoprotein(a) Concentration in Children with Steroid-Sensitive Nephrotic Syndrome
Authors: Kawasaki Yukihiko , Suzuki Junzo , Nozawa Ruriko , Suzuki Shigeo , Suzuki Hitoshi
Published: April 2003

Aim: To clarify whether plasma lipoproteins, including Lp(a), can predict relapse pattern in the first years after diagnosis of nephrotic syndrome (NS), we evaluated them in patients with steroid-sensitive NS. Methods: We analyzed the medical records of 35 patients with steroid-sensitive NS who were seen by us from January 1992 to December 1999 followed for at least 1 year. These patients were divided into two groups. Group 1 consisted of 20 patients who infrequently relapse (IR: <2 in 6 months or <3 in a year), group 2 consisted of 15 patients who frequently relapse (FR: ≥2 in 6 months or ≥3 in a year). Clinical and laboratory findings such as age at onset, gender, urinalysis, serum level of total protein, albumin, and concentrations of serum lipid including lipoprotein(a) (Lp(a)) were investigated between group 1 and group 2. Results: The concentration of plasma Lp(a) in group 2 was higher than that in group 1 (81.0 ± 35.2 vs. 35.9 ± 26.5 mg/dl, p < 0.01). On multivariate analysis using logistic regression model, the concentration of plasma Lp(a) was an independent risk factor for relapse of NS. Conclusions: Our findings suggest that of all the laboratory data examined, high values of Lp(a) can predict future relapse of NS and should be well documented.
Combined Irinotecan, Oxaliplatin and 5-Fluorouracil in Patients with Advanced Colorectal Cancer
Authors: Calvo Emiliano , Cortés Javier , González-Cao María , Rodríguez Javier , Aramendía José Manuel , Fernández-Hidalgo Óscar , Martín-Algarra Salvador , Salgado José Esteban , Martínez-Monge Rafael , de Irala Jokin , Brugarolas Antonio
Published: April 2003

Objectives: To evaluate the feasibility and a possible activity range of combination irinotecan (CPT-11), oxaliplatin, and 5-FU in advanced colorectal cancer (ACC). Patients and Methods: A total of 53 patients (51% chemoresistant) were treated. Twenty-eight received monthly intravenous oxaliplatin (120 mg/m2) and CPT-11 (250 mg/m2) on day 1 and a course of 5-FU; these constituted the IRI250 group. Twenty-five received monthly intravenous oxaliplatin (120 mg/m2), CPT-11 (300 mg/m2) on day 1, and a course of 5-FU (IRI300 group). 5-FU administration was carried out as follows. Those with predominant hepatic disease (n = 32) received an intra-arterial infusion of 5-FU (2,500 mg/day on days 1–4); these were the IA-FU group. The remaining 21 patients received intravenous 5-FU (2,600 mg/m2 plus leucovorin 500 mg/m2 on days 1 and 15); these constituted the IV-FUFOL group. Results: Intention-to-treat response rate was 54.7% (4 CR, 7.5%). Twelve patients (22.5%) had stable disease; only 4 (7.5%) progressed. Median progression-free and overall survivals were 10 and 18 months, respectively. One-year progression-free and overall survival rates were 44.3 and 67.4%, respectively. Grade 3–4 toxicities included diarrhea (45.3% of patients), neutropenia (52.8%), mucositis (13.2%), and emesis (11.3%). There were 3 treatment-related deaths (5.7%), all in the IA-FU/IRI300 subgroup. Severe adverse effects requiring chemotherapy dose adjustment were observed in 67.9% of the patients, with odds ratios 9.04-fold higher in the IA-FU/IRI300 group (95% CI: 1.07–76.20) and 0.23-fold lower in the IV-FUFOL/IRI250 group (95% CI: 0.05–0.97). Conclusion: This combination seems to have substantial activity in ACC. Overall toxicity was unacceptable in the IA-FU and IRI300 groups, with diarrhea and cytopenia constituting the dose-limiting side effects. Tolerance and efficacy profiles achieved with IV oxaliplatin (120 mg/m2 day 1), IV CPT-11 (250 mg/m2 day 1) and IV 5-FU 2.6 g/m2 with IV leucovorin (500 mg/m2 days 1 and 15) was favorable and deserves further investigation.
Enhanced Ocular Anti-Inflammatory Activity of Ibuprofen Carried by an Eudragit RS100® Nanoparticle Suspension
Authors: Bucolo Claudio , Maltese Adriana , Puglisi Giovanni , Pignatello Rosario
Published: April 2003

Purpose: To investigate the ocular pharmacodynamic profile of a polymer nanoparticle system loaded with sodium ibuprofen (IBU-RS) in comparison to an aqueous solution of ibuprofen lysinate (IBL) in the rabbit eye both being applied topically. Methods: Ocular inflammation was elicited by topical application of sodium arachidonate. Inflammation was quantified according to a modified Draize test. The protein level and the number of polymorphonuclear leukocytes in the aqueous humor were assessed after 2 h from arachidonate instillation. The ibuprofen concentration in the aqueous humor was evaluated by HPLC assay. The physico-chemical properties of nanoparticles were also evaluated. Results: The IBU-RS nanosuspension formulation significantly reduced the primary signs of ocular inflammation as well as significantly reducing the protein level and the number of polymorphonuclear leukocytes in the aqueous humor compared with the IBL formulation. Furthermore, the aqueous humor drug concentration from the group treated with IBU-RS was significantly higher compared to the IBL-treated group. The IBU-RS nanosuspensions showed very interesting size and surface charge values, adequate for ophthalmic administration. Conclusions: The pharmacological profile of the topical IBU-RS nanosuspension formulation described in this study indicates that the dispersion of the drug within RS polymer nanoparticles increased its ocular bioavailability and ultimately its pharmacological activity.
Skin Genetically Engineered as a Bioreactor or a ‘Metabolic Sink’
Authors: Christensen Rikke , Jensen Uffe Birk , Jensen Thomas G.
Published: April 2003

Genetically manipulated human keratinocytes can produce and secrete medically relevant proteins to the circulation. Genetically modified skin may also function as a ‘metabolic sink’ detoxifying the body of metabolites which accumulate in certain metabolic diseases. At the National Institutes of Health (NIH), Bethesda, Md., a clinical trial investigating the treatment of an ocular disease using the skin as a ‘metabolic sink’ for ornithine accumulating in gyrate atrophy patients is being prepared. The trial will involve the transplantation of a small patch of autologous keratinocytes, transduced ex vivo, onto the thighs of patients with gyrate atrophy. We are now investigating other diseases where this technology may be applicable such as in the treatment of hyperphenylalaninemia or hypercholesterolemia.
Charcot-Marie-Tooth Disease in Molise, a Central-Southern Region of Italy: An Epidemiological Study
Authors: Morocutti Cristoforo , Colazza Giovanni Battista , Soldati Giampiero , D’Alessio Carmelo , Damiano Maria , Casali Carlo , Pierelli Francesco
Published: April 2003

An epidemiological survey of Charcot-Marie-Tooth disease (CMT) was conducted in Molise, a central-southern region of Italy, from March 1998 to June 2000. Fifty-eight cases of CMT in 13 unrelated families were identified within the selected area. The prevalence of all subtypes of CMT was 17.5/100,000. All families underwent a bio-molecular analysis to disclose the duplication at gene locus 17p11.2 in order to ascertain the diagnosis of CMT type 1A. Our data revealed that 64% of all the observed patients had CMT1A, thus confirming the high prevalence of duplication of the 17p11.2 locus.
Numerous Proteins in Mammalian Cells Are Prone to Iron-Dependent Oxidation and Proteasomal Degradation
Authors: Drake Steven K. , Bourdon Emmanuel , Wehr Nancy B. , Levine Rodney L. , Backlund Peter S. , Yergey Alfred L. , Rouault Tracey A.
Published: April 2003

The mechanisms that underlie iron toxicity in cells and organisms are poorly understood. Previous studies of regulation of the cytosolic iron sensor, iron-regulatory protein 2 (IRP2), indicate that iron-dependent oxidation triggers ubiquitination and proteasomal degradation of IRP2. To determine if oxidization by iron is involved in degradation of other proteins, we have used a carbonyl assay to identify oxidized proteins in lysates from RD4 cells treated with either an iron source or iron chelator. Protein lysates from iron-loaded or iron-depleted cells were resolved on two-dimensional gels and these iron manipulations were also repeated in the presence of proteasomal inhibitors. Eleven abundant proteins were identified as prone to iron-dependent oxidation and subsequent proteasomal degradation. These proteins included two putative iron-binding proteins, hNFU1 and calreticulin; two proteins involved in metabolism of hydrogen peroxide, peroxiredoxin 2 and superoxide dismutase 1; and several proteins identified in inclusions in neurodegenerative diseases, including HSP27, UCHL1, actin and tropomyosin. Our results indicate that cells can recognize and selectively eliminate iron-dependently oxidized proteins, but unlike IRP2, levels of these proteins do not significantly decrease in iron-treated cells. As iron overload is a feature of many human neurological diseases, further characterization of the process of degradation of iron-dependently oxidized proteins may yield insights into mechanisms of human disease.
Interactions of Iron with Reactive Intermediates of Oxygen and Nitrogen
Authors: Nappi Anthony J. , Vass Emily
Published: April 2003

Iron not only functions as a cofactor for various enzymes, but it is also a source of potentially cytotoxic molecules produced through interactions with certain reactive intermediates of oxygen (ROI) and nitrogen (RNI). Protection from such iron-mediated damage results in large part from homeostatic mechanisms that regulate the sequestration of iron. Perturbations in iron homeostasis can result in an array of adverse cellular manifestations including oxidative and nitrosative stress, enhanced production of free radicals, macromolecular damage, and cell death. This brief review focuses on some of the potentially adverse reactions of iron with ROI and RNI.
Diagnostic Yield of Mediastinal Exploration
Authors: Hajjar Waseem , Elmedany Yasser , Bamousa Ahamed , Saladein Moataz , Ashour Mahmoud , Fouda Mohammed , Al-Kattan Khaled
Published: April 2003

Objective: To report our experiences of surgical diagnostic procedures in patients with unidentified mediastinal pathology. Methods: From July 1995 to July 1999, 72 patients with mediastinal pathology had 73 surgical procedures for the purpose of tissue diagnosis. Of the 72 patients, 39 were female and 33 male, with an average age of 54 years. Mediastinoscopy and anterior mediastinotomy were performed in 54 and 15 patients, respectively (13 left and 2 right). Thoracoscopy was used in 3 cases, and 2 patients were diagnosed via cervical incision. Superior vena cava (SVC) obstruction was noted in 4 patients and four procedures were repeat procedures. Frozen section analysis was performed in 52 cases. Results: Tissue diagnosis was achieved in all cases, enabling a specific diagnosis in 70 cases (97%). In 2 patients, the final diagnosis was non-specific and in 1 patient repeat biopsy was needed. The diagnoses were lymphoma (n = 32), tuberculosis (n = 20), metastatic disease (n = 11) and other pathology (n = 9). There was no operation-related mortality although 1 patient developed mediastinal haematoma, which was treated conservatively. The 2 in-hospital deaths resulted from causes secondary to the primary disease (invasive aspergilloma or Hodgkin’s lymphoma). Conclusion: Mediastinoscopy is a safe surgical procedure with high diagnostic yield. Its routine use with mediastinotomy and thoracoscopy ensures accurate diagnosis. Careful surgical technique is mandatory in repeat procedures and SVC obstruction cases.
A 72-bp Internal Deletion in the Left Inverted Terminal Repeat of the Bovine Adenovirus Type 3 Genome Does Not Affect Virus Replication
Authors: van Olphen Alberto L. , Mittal Suresh K.
Published: April 2003

The genome of bovine adenovirus type 3 (BAV3) is flanked by 195-base pair (bp) inverted terminal repeats (ITR). We isolated a BAV3 mutant (BAV3c29) having an internal deletion within the left ITR. The deletion eliminated 72 bp between nucleotides (nt) 89 and 162, including most of the GC-rich sequences located close to the end of the ITR sequences. This deletion did not seem to have any affect on the virus plaque size or morphology and the kinetics of viral replication compared to wild-type (wt) BAV3. The nt sequence of the right ITR of BAV3c29 remained identical to the right or left ITR of wt BAV3. These results indicate that the cis-acting sequences present within the 72 bp between nt 89 and 162 of the left ITR are not essential for BAV3 DNA replication in cultured cells.
Modification of Acute and Late-Phase Allergic Responses to Ovalbumin with Lipopolysaccharide
Authors: Tulic Meri K. , Holt Patrick G. , Sly Peter D.
Published: April 2003

Background: We have previously shown that lipopolysaccharide (LPS) exposure in sensitised animals 18 h after ovalbumin (OVA) challenge inhibits OVA-induced airway hyper-responsiveness (AHR). In the present study, we investigated the effect of LPS on OVA-induced acute and late-phase allergic responses in sensitised rats when challenged with OVA. Methods: Rats were sensitised with OVA and 11 days later challenged with 1% OVA in the presence or absence of LPS (0.5–50 µg/ml) given in the same nebulizer. Acute responses to OVA were measured each minute for 30 min after challenge. In a separate group of animals, late-phase responses to OVA were determined at 24 h. At the end of each study, Evans blue dye was injected and animals sacrificed 30 min later. Bronchoalveolar lavage was obtained to monitor inflammatory cell migration and microvascular leakage. Results: OVA challenge in sensitised animals produced an acute response with changes in lung mechanics peaking 10.0 ± 0.9 min after OVA and returning to baseline within 30 min. This was followed 24 h later by increased responses to methacholine chloride (MCh), inflammatory cell influx and increased Evans blue leakage into the lungs. Presence of 5 or 50 µg/ml LPS in the nebulizer during OVA challenge altered the kinetics of the acute-phase response, with an immediate decrease in lung function (time to peak decreased from 10.3 ± 1.2 to 1.8 ± 0.2 and 2.2 ± 0.3 min, respectively: p < 0.001, n = 6) and a dose-dependent attenuation of late-phase AHR, cellular influx (n = 5, p < 0.001) and Evans blue leakage (n = 5, p < 0.001) at 24 h. Conclusions: In summary, co-administration of OVA with LPS modifies both the acute and late-phase responses to the allergen, inducing an earlier acute change in lung function and a dose-dependent inhibition of late-phase responses to the allergen.
Petasins in the Treatment of Allergic Diseases: Results of Preclinical and Clinical Studies
Authors: Thomet O.A.R. , Simon H.-U.
Published: April 2003

Plant extracts are causing an increased interest in the treatment of many chronic diseases, including asthma and other allergic diseases. Several laboratories characterized petasins (petasin, isopetasin, and neopetasin) isolated from extracts of butterbur (Petasites hybridus) as pharmacologically active components, which inhibit leukotriene synthesis in leukocytes. The molecular mechanisms by which petasins abrogate inflammatory effector cell functions have, at least partially, been identified. In vitro studies revealed that petasins may have several intracellular targets and this may depend on the stereoisomer used. In an open clinical trial in patients suffering from allergic rhinitis, a reduction of leukotriene and histamine levels in nasal fluids was associated with the butterbur extract administration. To better evaluate the clinical value in this particular allergic disease, the clinical efficacy of the drug was compared with an established antihistamine treatment scheme in a double-blind study; no significant difference was observed between the two treatment groups. In this article, we critically review recently published work and summarize the current stage in the pharmacological characterization of butterbur extracts.
Prevention of Early Mutans Streptococci Transmission in Infants by Professional Tooth Cleaning and Chlorhexidine Varnish Treatment of the Mother
Authors: Gripp Vivian C. , Schlagenhauf Ulrich
Published: April 2003

Mutans streptococci (MS) are transmitted in early childhood from the mother to the infant, mostly by saliva. This study evaluated the influence of chlorhexidine (CHX) varnish-mediated suppression of MS in mothers with high salivary MS counts on the frequency of MS colonization in their children at 2 years of age. Professional tooth cleaning followed by CHX varnish application in 16 mothers with high salivary MS counts resulted in a significantly lower number of MS-colonized infants at 2 years of age when compared to a control group of 13 untreated mother-child pairs with high maternal salivary MS levels. The frequency of MS colonization in the CHX-treated group was not significantly different from the one found in a negative control group of 15 mother-child pairs with low maternal salivary MS levels.
Leisure Sickness: A Pilot Study on Its Prevalence, Phenomenology, and Background
Authors: Vingerhoets Ad J.J.M. , van Huijgevoort Maaike , van Heck Guus L.
Published: April 2003

Aim: To explore the prevalence, phenomenology, and background of leisure sickness, i.e., the condition of people developing symptoms of sickness during weekends and/or vacations. Method: In order to obtain an estimate of its prevalence, a representative Dutch sample consisting of 1,128 men and 765 women was asked to indicate to what extent they recognized themselves in our description of weekend and vacation sickness. For the investigation of the phenomenology and background of this condition and the characteristics of the patients suffering from it, questionnaire data were collected in new samples consisting of 114 cases and 56 controls. Questions referred to symptoms, onset, duration, appreciation of weekend and vacation activities, and appraisal of work and workload. Results: In the case of male respondents, 3.6 and 3.2% recognized themselves in the description of the weekend and the vacation syndrome, respectively, compared with 2.7 and 3.2% women. Most frequently reported symptoms were headache/migraine, fatigue, muscular pains, and nausea. In addition, viral infections (flue-like, common cold) were often reported in relation to vacations. Cases had generally suffered from leisure sickness for over 10 years and the onset was associated with stressful conditions. They attributed their condition to difficulties with the transition from work to nonwork, stress associated with travel and vacation, as well as workload and personality characteristics. There were no significant group differences in the appreciation of weekend and leisure activities or lifestyle during days off. Most striking differences were found with respect to experienced workload, sense of responsibility, and inability to relax. Conclusion: Leisure sickness is a relatively common condition. Specific lifestyle factors or leisure activities seem to be less relevant for its development. Concerning risk factors, the data tend to point to high workload and person characteristics, namely, the inability to adapt to the nonworking situation, a high need for achievement, and a high sense of responsibility with respect to work. Future studies should be designed for testing specific hypotheses concerning the underlying mechanisms and evaluating the effectiveness of psychological and/or physical activity interventions.
Emotional Stress, Psychosocial Variables and Coping Associated with Hepatitis C Virus and Human Immunodeficiency Virus Infections in Intravenous Drug Users
Authors: Grassi Luigi , Satriano James , Serra Alessia , Biancosino Bruno , Zotos Spyridon , Sighinolfi Laura , Ghinelli Florio
Published: April 2003

Background: The increasing health problem of hepatitis C virus (HCV) infection has only recently attracted the attention of psychosocial research, especially among subjects at higher risk (e.g. intravenous drug users; IDUs). The aim of the present study was to compare emotional stress symptoms, psychosocial variables (i.e. social support, external locus of control and emotional repression) and coping strategies in HCV-seropositive, human immunodeficiency virus (HIV)-seropositive and HCV/HIV-noninfected IDUs. Methods: IDUs followed by the Infectious Diseases Outpatient clinic were enrolled in the study over a period of 1 year. HCV-positive (n = 62) and HIV-positive (n = 76) IDUs and HCV/HIV-seronegative IDUs (n = 152) completed the Brief Symptom Inventory, the Social Provision Scale, the Locus of Control scale and the affective inhibition scale of the Illness Behavior Questionnaire. Coping with illness among HCV-positive and HIV-positive subjects was assessed through a modified version of the Mental Adjustment to Cancer Scale. Results: No significant differences were found between the samples with respect to individual and interpersonal variables. HCV-positive subjects showed higher scores on several psychological stress dimensions (i.e. obsessive-compulsive, phobic anxiety, paranoid ideation, psychoticism) and lower scores on fighting spirit, hopelessness and anxious preoccupation towards illness than HIV-positive patients. HCV-positive and HCV/HIV-seronegative IDUs reported comparable scores on most of the psychological measures. Conclusions: The findings indicate that routine assessment of psychosocial variables and coping mechanisms should be integrated into all HCV and HIV services, especially those dedicated to treatment of patients with substance abuse, as a vulnerable segment of the population at risk for life-threatening physical illness such as HCV and HIV infections.
A Community-Based Psychoeducational Group Approach to Hypochondriasis
Authors: Bouman Theo K.
Published: April 2003

Background: This open trial investigates the feasibility and effectiveness of a cognitive-educational approach to hypochondriasis in a self-referred community sample. Method: Twenty-seven of 43 interested applicants fulfilled DSM-criteria for hypochondriasis and resembled a hypochondriacal reference group according to the Groningen Illness Attitude Scale. Subjects participated in small groups for six 2-hour sessions aimed at educating them about hypochondriasis. Results: The results showed that the 21 completers improved between pre- and post-test on parameters for hypochondriasis and depression, and that this improvement was maintained at 4 weeks and 6 months follow-up. Six subjects dropped out for various reasons, showing no decrease in relevant variables. Conclusion: Hypochondriacal subjects can be reached outside mental health settings, and a psychoeducational group approach may be an acceptable and effective method to reduce hypochondriacal psychopathology.
Explaining Attitudinal Ratings of Dutch Rising Contours: Morphological Structure vs. the Frequency Code
Authors: Rietveld Toni , Haan Judith , Heijmans Linda , Gussenhoven Carlos
Published: April 2003

In this article, two hypotheses were tested to explain attitudinal ratings like SURPRISE, SUGGESTION, REMINDER etc. of four rising nuclear contours observed in a Dutch question corpus and described as (a) H*L H%, (b) H* H%, (c) L*H H% and (d) L* H%. According to one hypothesis, the middle tones in (a) and (c) should be parcelled out, such that their absence produces contours (b) and (d), respectively, predicting communality of meaning within (a, c) that excludes (b, d). That is, (b, d) could be viewed as undershot variants of (a, c), with undershoot expressing a shade of meaning different from that of the fully realised pitch accents. This hypothesis was not confirmed by the data, though. The other hypothesis was based on the concept of the ‘frequency code’, which associ ates high/rising F₀ values with non-assertive behaviour and appeared to provide a much better model to predict listeners’ ratings.
Apoptotic and Proliferative Index after Alpha-1-Adrenoceptor Antagonist and/or Finasteride Treatment in Benign Prostatic Hyperplasia
Authors: Erdoğru Tibet , Ciftcioglu M. Akif , Emreoglu Ibrahım , Usta Mustafa F. , Koksal Turker , Ozbilim Gülay , Gulkesen K. Hakan , Baykara Mehmet
Published: April 2003

Introduction: The induction of apoptosis has emerged as a potential target for optimization of the medical management of benign prostatic hyperplasia (BPH), recently. The influence of α1-adrenoceptor antagonist (α1-ARA), 5-α reductase inhibitor and their combination on prostatic cell apoptotic and proliferative indices of benign hyperplastic prostate gland were investigated. Material and Methods: A total of 49 male patients with BPH (mean age: 66.5 years) treated with α1-ARA and/or finasteride were retrospectively evaluated. Patients treated with α1-ARA (doxazosin n = 12 and terazosin n = 10), finasteride (n = 9) and combination of finasteride and α1-ARA (n = 9) were enrolled in the study. Primary antibodies were Ki-67 and proliferating cell nuclear antigen for the evaluation of proliferation in prostate stromal and epithelial cells. In situ apoptotic DNA fragmentation was evaluated using TUNEL assay. Results: All treatment groups had no significant changes in the rate of prostate stromal and epithelial cell proliferation. Epithelial apoptotic index (AI) was not statistically significant for finasteride vs. α1- ARA, α1-ARA vs. finasteride + α1-ARA and finasteride + α1-ARA vs. finasteride groups. While α1-ARA was more effective than finasteride on stromal apoptosis, α1-ARA-induced stromal apoptosis was not significantly different from α1-ARA plus finasteirde treatment. Conclusion: Not only androgen variabilities but also alterations in sympathetic neurotransmission with age could have important implications for pathophysiological prostate growth. The combination of finasteride and α1-ARA is not superior to α1-ARA therapy with their similar epithelial and stromal apoptotic effects with unaffected cell proliferation.