bluuebunny/crossref_metadata_2025_split huggingface dataset:
Are Adverse Effects of Sildenafil also Caused by Inhibition of Diamine Oxidase?
Authors: Wantke F. , Hemmer W. , Focke M. , Stackl W. , Götz M. , Jarisch R. 
Published: April 2003

<i>Background:</i> Sildenafil citrate (Viagra), a drug used to treat erectile dysfunctions, causes adverse reactions such as headache, flushing or nasal congestion. Sildanefil’s potency as inhibitor of diamine oxidase was investigated, as side effects may also be induced by histamine itself due to an impaired histamine metabolism. <i>Methods:</i> Placental diamine oxidase inhibition experiments were performed with consecutive dilutions of sildenafil citrate (10<sup>–5</sup> to 10<sup>–9</sup> mol/l). In 9 male volunteers in vivo diamine oxidase inhibition was investigated after taking 100 mg sildenafil (Viagra). <i>Results:</i> Sildenafil citrate did not inhibit placental diamine oxidase either in vitro or in vivo. However, infusion of 300 mg of cimetidine inhibited diamine oxidase activity by 27 ± 7% 15 min after infusion, demonstrating that drugs may inhibit diamine oxidase in vivo. <i>Conclusion:</i> As side effects of sildenafil are not caused due to inhibition of diamine oxidase, sildenafil citrate seems to be harmless for patients suffering from histamine intolerance.
Blood Pressure and Risk of Dementia: Results from the Rotterdam Study and the Gothenburg H-70 Study
Authors: Ruitenberg Annemieke , Skoog Ingmar , Ott Alewijn , Aevarsson Olafur , Witteman Jaqueline C.M. , Lernfelt Bodil , van Harskamp Frans , Hofman Albert , Breteler Monique M.B. 
Published: April 2003

The association between blood pressure and dementia is debated. Results from population-based studies on blood pressure and dementia are inconclusive, and most are performed in subjects younger than 80 years of age. We examined the relation between blood pressure and dementia and the possible effect modification of this relation by age in a pooled dataset based on two prospective population-based studies. Subjects came from the Rotterdam study (n = 6,668), a longitudinal population-based study among subjects aged 55 years and over, and from the Gothenburg H-70 Study (n = 317), a study on subjects aged 85 years at baseline. Screening and diagnostic procedures for assessment of dementia were similar at baseline and follow-up and comparable between studies. We estimated relative risks of dementia using Cox proportional hazards regression analysis, adjusted for age, gender and study location. The average follow-up was 2.1 years. During this period, 196 subjects developed dementia. The risk of dementia decreased with increasing blood pressure level (per 10 mm Hg systolic blood pressure: RR = 0.93, 95% CI = 0.88–0.99; per 10 mm Hg diastolic blood pressure: RR = 0.89, 95% CI = 0.79–1.00). This association was confined to subjects who used anthypertensive medication. Persons who were demented at baseline had a stronger blood pressure decline during follow-up than those who were non-demented. This study suggests an inverse association between blood pressure and dementia risk in elderly persons on antihypertensive medication. Possibly, they may need higher blood pressure levels to maintain an adequate cerebral perfusion. Alternatively, lower blood pressure may be secondary to brain lesions in preclinical stages of dementia.
Duodenal Gangliocytic Paraganglioma as a Radiological Moving Defect
Authors: Kotsis Thomas , Voros Dionysios , Paphiti Agathi , Frangou Matrona , Mallas Elias 
Published: April 2003

<i>Background:</i> Gangliocytic paraganglioma of the duodenum is a peculiar neuroendocrine tumor, often revealed as an incidental radiographic finding or as a result of gastrointestinal hemorrhage, due to frequent ulceration of the overlying mucosa. Most lesions are pedunculated and submucosal with distinctive histology, consisting of endocrine, ganglion and spindle-shaped Schwann cells. <i>Methods:</i> A case of a duodenal gangliocytic paraganglioma is reported in a 50-year-old woman presenting with episodes of melena. Enteroclysis revealed a pedunculated tumor observed either in the second or third portion of the duodenum. Upper gastrointestinal endoscopy revealed a pedunculated ulcerated tumor which was subsequently confirmed by computed tomography. The tumor was simply excised through a duodenotomy. <i>Results:</i> The size of the tumor was 4.5 × 3 × 1.5 cm. Immunohistochemical and ultrastructural features of the tumor classified it as a typical duodenal gangliocytic paraganglioma with positive cellular reaction for neuron-specific enolase, chromogranin, somatostatin, gastrin and S100. <i>Conclusion:</i> Forty-six months after surgery, the patient is well with no evidence of recurrence. The majority of the reported duodenal gangliocytic paragangliomas were of bening nature. However, the fact that in 4 isolated cases there was lymph node involvement indicates that thorough investigation for lymph node metastases is needed, as well as thorough postoperative follow-up.
Taurine Prevents Interleukin-2-Induced Acute Lung Injury in Rats
Authors: Abdih H. , Kelly C.J. , Bouchier-Hayes D. , Barry Mary , Kearns S. 
Published: April 2003

<i>Background:</i> The therapeutic efficacy of interleukin-2 (IL-2) has been limited by a dose-dependent vascular leak syndrome. This may be related to neutrophil-mediated endothelial injury. Taurine has been shown to decrease this injury in vitro. This study investigates the role of taurine in preventing IL-2-induced lung injury, and the role of neutrophil-endothelial interactions in mediating this injury. <i>Methods:</i><i>Study 1:</i> Sprague-Dawley rats (n = 12/groups) were randomised to controls, IL-2-treated (1 × 10<sup>6</sup> units), and IL-2-treated with taurine (4% solution, orally for 48 h prior to IL-2 therapy). Lung injury was measured by extravascular lung water (wet/dry weight) and bronchoalveolar lavage protein concentration. Neutrophil infiltration was evaluated by measuring myeloperoxidase activity and bronchoalveolar lavage neutrophil concentration. <i>Study 2:</i> Rats (n = 10/group) were randomised into the same groups as study 1. Neutrophil-endothelial interactions in mesenteric vessels were assessed by intravital microscopy at half-hourly intervals. <i>Results:</i> Taurine reduced IL-2-induced acute lung injury as reflected by a decrease in wet-to-dry lung weight ratio from 7.2 ± 0.5 in the IL-2 group to 4.7 ± 0.3 in the taurine group (p < 0.05), and a decrease in bronchoalveolar neutrophil concentration from 823 ± 19.5 in the IL-2 group to 538 ± 18 in the taurine group (p < 0.05). Intravital microscopy demonstrated that IL-2 increased leucocyte adhesion and migration in mesenteric vessels, and that this was significantly reduced by taurine. <i>Conclusion:</i> These data suggest that taurine prevents IL-2-induced tissue injury in part by decreasing neutrophil-endothelial interactions.
Role of Apoptosis and Bcl-2/Bax in the Development of Tubulointerstitial Fibrosis during Experimental Obstructive Nephropathy
Authors: Zhang G. , Oldroyd S.D. , Huang L.H. , Yang B. , Li Y. , Ye R. , El Nahas A.M. 
Published: April 2003

<i>Background/Aims:</i> To examine the role of apoptosis in experimental unilateral ureteral obstruction (UUO). <i>Methods:</i> Rat kidneys were examined 3, 7 and 11 days following UUO or sham operation (SO). Tissue was immunohistochemically stained for α-smooth muscle actin (α-SMA), proliferating cell nuclear antigen (PCNA), Bcl-2 and Bax proteins. Apoptotic analysis was carried out in kidney sections using in situ end labelling of endonuclease cleaved DNA. <i>Results:</i> The relative volume (Vv) of cortical interstitium and interstitial α-SMA increased progressively following UUO. ED1-positive monocytes/macrophages peaked at day 7 and significantly decreased at day 11. PCNA-positive cells in tubulointerstitium were significantly increased on day 3. Staining returned to the level of the SO group by day 11, meanwhile those in the interstitium remained much higher than baseline. TUNEL-positive cells were persistently raised following UUO. Transient tubular cell proliferation seemed unable to counteract the apoptosis since tubular atrophy was apparently present by day 11 of UUO. However, interstitial cell proliferation was high enough to overwhelm apoptosis, particularly with respect ot myofibroblasts, since α-SMA immunostaining and Vv remained elevated. The ratio of the number of PCNA-positive cells to apoptotic cells formed a predictive pattern for the staining score of interstitial α-SMA (R<sup>2</sup> = 47.23%, p < 0.05) and Vv (R<sub>2</sub> = 49.93%, p < 0.05). Tubular Bcl-2 immunostaining peaked on day 3, and then gradually decreased to baseline by day 11. The expression of Bax protein was inhibited on day 3 when compared with that of the SO group, but increased with time following UUO. <i>Conclusion:</i> These findings suggest an important role for apoptosis and its regulatory proteins in the processes of tubular atrophy and fibrogenesis following UUO.
Volume Regulation of Thick Ascending Limb of Henle Cells: Significance of Organic Osmolytes
Authors: Grunewald R. Willi , Fahr Milena , Fiedler G. Martin , Jehle Peter M. , Müller Gerhard Anton 
Published: April 2003

The thick ascending loop of Henle (TALH) is exposed to high osmotic stress, which is particularly due to high sodium and chloride reabsorption and very low water permeability of the luminal membrane. Therefore, the volume regulation of TALH cells, derived from the TALH loop of rabbit kidneys, was analyzed. The volume was determined by impedance measurements. TALH cells, which were adapted to different osmolarities (300 and 600 mosm/l), showed no significant differences in their cell volume. Therefore, a complete volume regulation could be supposed. An increase in extracellular osmolarity from 300 to 600 mosm/l (osmolarity adjusted by addition of 150 m<i>M</i> NaCl) immediately led to a reduction in the cell volume by 37 ± 6% (n = 6). A regulatory volume increase (RVI) was not observed within 10 min but after 24 h. Conversely, a sudden cell swelling by 44 ± 5% (n = 4) was detected within 20 s following an extracellular hypoosmotic challenge (from 600 to 300 mosm/l). The subsequent volume regulatory decrease (RVD) required a period of 7 days. Specific inhibitors of important ion transporters had no effect on volume regulation. Thus, changes in the ion conductivity do not seem to influence the processes of RVI and RVD. Conversely, the intracellular content of the organic osmolytes, sorbitol, inositol, betaine, and glycerophosphorylcholine, changed in the course of RVI and RVD. These results provide evidence that TALH cells are capable of maintaining their volume despite large extracellular osmotic changes. RVI and RVD are mainly regulated by changes in the intracellular content of organic osmolytes within 1 and 7 days.
Decreased Glomerular Expression of Agrin in Diabetic Nephropathy and Podocytes, Cultured in High Glucose Medium
Authors: Yard B.A. , Kahlert S. , Engelleiter R. , Resch S. , Waldherr R. , Groffen A.J. , van den Heuvel L.P.W.J. , van der Born J. , Berden J.H.M. , Kröger S. , Hafner M. , van der Woude F.J. 
Published: April 2003

<i>Aim:</i> A decrease in glomerular heparan sulfate (HS) proteoglycan (PG), without apparent decrease in HSPG core protein expression, has been reported to occur in diabetic nephropathy (DN). In most studies however, agrin, the major HSPG core protein in the glomerular basement membrane, has not been studied. This prompted us to study the glomerular expression of agrin in parallel to the expression of HS-glycosaminoglycans (GAG) in biopsies of patients with DN. Furthermore, the influence of glucose on agrin production in cultured podocytes and the expression of agrin in fetal kidneys was investigated. <i>Methods:</i> Cryostat sections of renal biopsies from patients with DN (n = 8) and healthy controls (HC, n = 8), were stained for agrin and HS-GAG. Sections of fetal kidneys were double stained for agrin and CD35 or CD31. Stainings were performed by indirect immunofluorescence (IIF). The production of agrin by cultured human podocytes was tested by ELISA and IIF. <i>Results:</i> The expression of agrin, detected by AS46, was significantly reduced in biopsies from patients with DN compared to HC (p < 0.01). Similar findings were observed when monoclonal antibody JM72 was used (p < 0.05). In addition, a significant reduction in the glomerular expression of HS-GAG was detected with JM403 in these patients (p < 0.01). Agrin is expressed in cultured podocytes, the expression hereof was reduced when the cells were cultured in the presence of 25 m<i>M D</i>-glucose (p < 0.01). In biopsies of human fetal kidneys, glomerular expression of agrin coincided with the expression of CD31. In early stages of glomerular differentiation there was a strong staining for agrin and CD31 while CD35 was only slightly positive. <i>Conclusions:</i> Our data argue against a selective dysregulation in HSPG sulfation in DN, but suggest a pivotal role for hyperglycemia in the downregulation of agrin core protein production.
Phosphate Depletion in Opossum Kidney Cells: Apical But Not Basolateral or Transepithelial Adaptions of Pi Transport
Authors: Barac-Nieto M. , Alfred M. , Spitzer A. 
Published: April 2003

Monolayers of opossum kidney (OK) cells are widely used as models for the renal proximal tubule. OK cells adapt to phosphate (Pi) depletion by increasing their capacity for apical and basolateral Na<sup>+</sup>-dependent Pi uptake. Because NMR-visible cell Pi was found to be decreased in Pi-deprived kidney cells, we suggested that up-regulation of basolateral Pi efflux also occurs during adaptation to Pi deprivation [<i>American Journal of Physiol</i> 1994;267:C915–919]. In order to test this hypothesis, we measured the cell Pi pool, basolateral Pi efflux and transepithelial Pi fluxes in OK cells grown on permeable plastic filters, exposed overnight to solutions containing either 0.5 m<i>M</i> (deprived) or 2.0 m<i>M</i> (replete) Pi or <sup>32</sup>Pi. Following steady state or acute loading with <sup>32</sup>Pi, the specific activity (SA) of cell Pi, the cell Pi pool and the basolateral efflux of <sup>32</sup>Pi were measured. In the steady state, a 2-fold increase in Pi uptake sustained the intracellular Pi pool at 85% of the control level (30 ± 5 nmol/mg) in spite of a decrease in extracellular Pi from 2 to 0.5 m<i>M</i>. When the extracellular Pi was acutely (1 h) reduced to 0.1 m<i>M</i>, the cell Pi pool decreased (to 3 ± 1 nmol/mg) both in cells previously adapted overnight to either 0.5 or to 2 m<i>M</i> Pi (p >0.3). The rates of absolute and fractional basolateral washout of cell <sup>32</sup>Pi after 1 h loading with 0.1 m<i>M</i><sup>32</sup>Pi were similar in cells adapted to 0.5 compared to 2 m<i>M</i> Pi. This indicates that Pi depletion did not affect the effective permeability of the basolateral membranes to Pi. Adaptation for 16 h to 0.5 compared to 2 m<i>M</i> Pi did not alter the rate of net transepithelial transport of 0.1 m<i>M</i> Pi from the apical to the basal compartment but reduced (p < 0.05) the unidirectional fluxes of both <sup>32</sup>Pi and <sup>14</sup>C-mannitol. An insufficient driving force (unchanged or low Pi concentration in the transport pool, low electrical or coupled-anion gradients) and a constant effective basolateral Pi permeability must have limited basolateral Pi efflux in cells exposed to 0.1 m<i>M</i> Pi. Thus, in OK cells grown on plastic support there are no adaptive increases in either basolateral Pi efflux, or in transcellular and paracellular Pi transport, in response to Pi depletion. Adaptations are limited to increases in apical and basolateral sodium-dependent Pi uptakes that can maintain the cell Pi pool as long as apical Pi is not too low (≧0.5 m<i>M</i>). The OK cells adapt to low Pi concentrations conserving cell Pi but not increasing basolateral Pi efflux nor transepithelial Pi transport.
The Effect of Different Growth Hormone Administration Frequencies on Growth in Growth Hormone-Deficient Patients
Authors: Cavallo L. , De Luca F. , Bernasconi S. , Arrigo T. , Gurrado R. , Zecchino C. 
Published: April 2003

In two different groups of clinically prepubertal children (bone age ≤8 years) with isolated growth hormone deficit we have evaluated either if the substitutive therapy administered by pump (permitting between 20.00 and 08.00 h the association of continuous and intermittent subcutaneous growth hormone administration) could improve growth (study A) or if a 3 times/week schedule treatment could be performed without any negative effect on growth with respect to 6 injections/week (study B). All patients had been previously successfully treated for at least 2 years by the same dose used during both studies (0.6 IU/kg/week) administered at bedtime 6 times/week. Study A: Each child underwent at bedtime both pump administration (6 months) and single daily injection (6 months). The circulating IGF-I pattern as well as the growth velocity and the ratio bone age increase/height age increase did not differ during the two treatment regimens. Study B: No differences were observed in auxological parameters during the treatment schedule on 3 times/week compared to the previous year on 6 times/week. In conclusion: Our treatment, consisting of the association of continuous and intermittent subcutaneous growth hormone administration, did not improve growth velocity with respect to single daily subcutaneous injection; the growth hormone administration 3 times/week, starting at the 3rd year of substitutive therapy or later, seems to have no negative effect on growth with respect to 6 injections/week.
Studies on the Role of Adhesive Proteins in Maintaining Pregnancy
Authors: Asahina Toshihiko , Kobayashi Takao , Okada Yoshichika , Itoh Mariko , Yamashita Miwa , Inamoto Yutaka , Terao Toshihiko 
Published: April 2003

It is well known that maternal fibrinogen (Fg) and factor X III are essential for maintaining early pregnancy. We studied their role by analysis of clinical reports and immunohistochemical investigation. <b>Methods:</b> (1) We analyzed the pregnancy cases of congenital afibrinogenemia and congenital factor X III deficiency. (2) Immunohistochemical staining of Fg, subunit A of factor X III (X III<sub>A</sub>) and fibronectin (Fn) were performed in the human implantation site, placenta, and endometrial cells cultured in serum-free medium. <b>Results:</b> (1) Afibrinogenemia needed to be administrated Fg from 4 weeks’ gestation (4 wG), and factor X III deficiency needed factor X III concentrate from 5 wG, in order to prevent abortion. (2) <i>Implantation tissues:</i> Fg, cellular X III<sub>A</sub> and Fn were present at the decidual stroma around invasive cytotrophoblasts at 5 wG. X III<sub>A</sub>-positive cells coincided with LN-5-positive macrophages. <i>Placenta:</i> Fg, cellular X III<sub>A</sub> and Fn were present in the decidual layer. <i>Endometrial culture cells:</i> Fn was secreted by spindle-like shaped cells. X III<sub>A</sub> was secreted by round-shaped cells. <b>Conclusion:</b> Maternal Fg and factor X III are essential just after 4∼5 wG, and in that period they and Fn are present abundantly in decidual stroma around invasive cytotrophoblasts. It is concluded that when cytotrophoblasts invade endometrium maternal Fg, factor X III and Fn are concerned with cytotrophoblasts’ anchoring as adhesive proteins.
Growth Hormone Response to a Growth Hormone-Releasing Hormone Stimulation Test in a Population-Based Study following Cranial Irradiation of Childhood Brain Tumors
Authors: Schmiegelow M. , Lassen S. , Poulsen H.S. , Feldt-Rasmussen U. , Schmiegelow K. , Hertz H. , Müller J. 
Published: April 2003

Children with brain tumors are at high risk of developing growth hormone deficiency (GHD) after cranial irradiation (CI) if the hypothalamus/pituitary (HP) axis falls within the fields of irradiation. The biological effective dose (BED) of irradiation to the HP region was determined, since BED gives a means of expressing the biological effect of various irradiation treatment schedules in a uniform way. Hypothalamic versus pituitary damage as cause of GHD was distinguished in 62 patients by comparing the growth hormone (GH) peak response to an insulin tolerance test (ITT)/arginine stimulation test and the GH response to a growth hormone-releasing hormone (GHRH) stimulation test. Peak GH response to a GHRH test was significantly higher (median 7.3 mU/l; range: 0.5–79.0 mU/l) than that of an ITT/arginine test (median 4.7 mU/l; range: 0.01–75.0 mU/l) (p = 0.017). Peak GH after a GHRH test was significantly inversely correlated to follow-up time (r<sub>s</sub> = –0.46, p < 0.0001) and to BED (R<sub>s</sub> = –0.28, p = 0.03), and both were found to be of significance in a multivariante regression analysis. We speculate that a significant number of patients developed hypothalamic radiation-induced damage to the GHRH secreting neurons, and secondary to this the pituitary gland developed decreased responsiveness to GHRH following CI in childhood.
Influence of Sex and Age at Onset on Autoantibodies against Insulin, GAD<sub>65</sub> and IA2 in Recent Onset Type 1 Diabetic Patients
Authors: Bilbao J.R. , Rica I. , Vázquez J.A. , Busturia M.A. , Castaño L. 
Published: April 2003

<i>Methods:</i> Autoantibodies against insulin (IAA), glutamic acid decarboxylase (GADA) and tyrosine phosphatase IA2 (IA2A) were measured in sera from 448 recent onset patients with type 1 diabetes mellitus (DM) subdivided according to sex (194 female and 254 male) and age at onset (134 patients diagnosed before 10 years, 187 between 10 and 20 years, 66 between 20 and 30 years and 61 over 30 years. <i>Results:</i> Autoantibodies were more frequent in female DM patients (93.8 vs. 86.6%, p = 0.013) due to an increased prevalence of both GADA (86.1 vs. 70.1%) and IA2A (59.3 vs. 49.2%), with GADA levels also significantly higher in women (0.24 vs. 0.18 U, p = 0.0003). When age groups were compared, there was a reduction in prevalence in patients over 20 years for both IAA (70% for patients diagnosed under 20 and 36% for older patients) and IA2A (65 and 25%, respectively). These differences also affected IAA levels, with the highest antibody titres in the youngest group (1,214.1 nU/ml in children under 10 compared to 546.9, 345.6 and 341.1 nU/ml in the subsequent groups; p < 10<sup>–4</sup>). GADA prevalence did not differ significantly between age groups but, nevertheless, autoantibody levels were highest among the oldest type 1 DM patients (0.327 U compared to 0.216, 0.197 and 0.176 U in the decreasing age groups; p < 10<sup>–4</sup>). <i>Conclusion: </i>There are sex- and age-related differences affecting the presence and/or titres of β cell autoantibodies. We speculate that these differences could reflect the severity and specificity of the autoimmune attack against the endocrine pancreas and might influence the rate of progression to type 1 DM or the risk of developing other autoimmune diseases.