bluuebunny/crossref_metadata_2025_split huggingface dataset:
Immobilization Stress Rapidly and Differentially Modulates BDNF and TrkB mRNA Expression in the Pituitary Gland of Adult Male Rats
Authors: Givalois Laurent , Marmigère Frédéric , Rage Florence , Ixart Guy , Arancibia Sandor , Tapia-Arancibia Lucia 
Published: April 2003

Brain-derived neurotrophic factor (BDNF) is a neurotrophin involved in neuronal survival and plasticity that binds to high-affinity receptors named TrkB. In the central nervous system, brain insults, including stress, induce modifications in BDNF messenger RNA (mRNA) expression. The present study attempted to determine in the adult rat pituitary, a peripheral structure relevant for the stress response: (1) whether BDNF and TrkB mRNA expression is influenced by different durations (15, 30, 60, 180 and 300 min) of single immobilization stress; (2) the expression of BDNF transcripts containing the different exons and their possible variations after stress exposure. Plasma corticotropin (ACTH) and corticosterone concentrations were strongly and significantly increased as early as 5 min after the stress stimulus. Using RNAse protection assay and in situ hybridization, a rapid increase in BDNF mRNA occurred at 15 min. This was accompanied by an increase in BDNF protein at 60 min, and by a rapid and significant decrease in TrkB mRNA expression observed at 15 and 30 min after stress application. RT-PCR analysis of BNDF transcripts showed strong basal expression of exons III and IV, whereas transcripts containing exons I and II seemed weakly expressed. After stress application, transcripts containing exons III and IV were rapidly and significantly increased at 30 min, whereas transcripts containing exons I and II remained unchanged. These results show that pituitary BDNF transcripts expression is differentially affected by immobilization stress.
Glomerular Cell Replication and Cell Loss through Apoptosis in Experimental Diabetes mellitus
Authors: Pesce Carlo , Menini Stefano , Pricci Flavia , Favre Anna , Leto Gaetano , DiMario Umberto , Pugliese Giuseppe 
Published: April 2003

<i>Aim:</i> To evaluate changes in the glomerular cell balance between replication and apoptosis in experimental diabetes mellitus (DM) in relation to morphometric data. <i>Methods:</i> Adult Sprague-Dowley rats with streptozotocin-induced DM and controls of the same age and strain were sacrificed 4 and 8 weeks and 6 months after disease onset. Cell replication was demonstrated with MIB-5, and apoptosis with the terminal uridine nick end labeling technique. Glomerular size and glomerular cell population were estimated morphologically. <i>Results:</i> Diabetic and control rats showed irrelevant MIB-5 positivity at all time points. Glomerular apoptosis was minimal in rats with 4 and 8 weeks of DM and in controls. Rats with 6 months of DM showed significantly higher glomerular apoptosis values than controls (2.49 ± 0.25 vs. 0.65 ± 0.16%; p < 0.001). The mean cell count per glomerular profile was significantly lower in these diabetic rats (64.02 ± 1.93 vs. 78.27 ± 0.99; p < 0.001), a change that correlated with that in apoptosis. The glomerular cell density was further decreased in diabetic rats because of the diabetic increase in mean glomerular volume (1.598 vs. 0.927 10<sup>6</sup> µm). <i>Conclusions:</i> Apoptosis is associated with loss of glomerular cells in rats with long-term, streptozotocin-induced DM and – to a considerably lower degree – in controls of the same age and strain. These changes could be relevant to glomerulosclerosis associated with long-term, streptozotocin-induced DM.
Trends in Hospitalized Stroke for Blacks and Whites in the United States, 1980–1999
Authors: Kennedy Byron S. , Kasl Stanislav V. , Brass Lawrence M. , Vaccarino Viola 
Published: April 2003

<i>Background:</i> Racial differences in stroke mortality are widely recognized, but it is unclear whether or not these differences are due mainly to blacks having a greater stroke incidence or higher case fatality rates compared to those of whites. <i>Objectives:</i> The aim of this study was to describe the race-specific US trends in hospital discharge rates and in-hospital mortality among stroke patients for the period 1980–1999. It was hypothesized that the hospital discharge rates and in-hospital mortality among stroke patients would be greater for blacks than for whites. <i>Methods:</i> Data from the National Hospital Discharge Survey for the period 1980–1999 were used to identify stroke subjects according to the codes of the <i>International Classification of Diseases</i>, ninth revision (codes 430–434 and 436). Direct standardization and Poisson regression were used to compare hospitalized stroke morbidity and mortality rates between blacks and whites. The main outcome measures were the number of stroke discharges and in-hospital deaths for black and white stroke patients. <i>Results:</i> Between the years 1980 and 1999, the hospital discharge rates for stroke increased for blacks (n = 8,700) and decreased for whites (n = 46,154); the in-hospital mortality rates decreased for both black and white stroke patients. Generally, the risk of a stroke hospitalization was greater for blacks than for whites by more than 70%, whereas both groups were similar in terms of in-hospital mortality rates among stroke patients. <i>Conclusions:</i> Differences between blacks and whites in terms of stroke mortality are more likely due to differences in stroke incidence rather than case fatality. These data imply that greater attention should be given to primary/secondary prevention and that additional research is needed to understand the reasons for these patterns.
Molecular Bases for the Actions of Ovarian Sex Steroids in the Regulation of Proliferation and Apoptosis of Human Uterine Leiomyoma
Authors: Matsuo Hiroya , Kurachi Osamu , Shimomura Yosuke , Samoto Takashi , Maruo Takeshi 
Published: April 2003

Uterine leiomyomas appear during the reproductive years and regress after menopause, indicating the ovarian steroid-dependent growth potential. In order to characterize the molecular mechanism of sex steroidal regulation of leiomyoma growth, we examined whether sex steroids could influence the proliferation of leiomyoma cells. As epidermal growth factor (EGF) has been shown to mediate estrogen action and play a crucial role in regulating leiomyoma growth, we also investigated the effects of sex steroids on EGF and EGF receptor (EGF-R) expression in leiomyoma cells. In cultures of leiomyoma cells, the addition of either estradiol (E<sub>2</sub>; 10 ng/ml) or progesterone (P<sub>4</sub>; 100 ng/ml) resulted in an increase in proliferating cell nuclear antigen (PCNA) expression in the cells, whereas in cultures of normal myometrial cells, the addition of E<sub>2</sub> augmented PCNA expression in the cells, but P<sub>4</sub> did not. Immunoblot analysis revealed that leiomyoma cells contained immunoreactive EGF and that P<sub>4</sub> treatment resulted in an increase in EGF expression in the cells, whereas E<sub>2</sub> treatment resulted in a lower EGF expression in the cells. By contrast, E<sub>2</sub> treatment augmented EGF-R expression in cultured leiomyoma cells, but P<sub>4</sub> did not. These results indicate that P<sub>4</sub> upregulates the expression of PCNA and EGF in leiomyoma cells, whereas E<sub>2</sub> upregulates the expression of PCNA and EGF-R in those cells. It is, therefore, conceivable that P<sub>4</sub> and E<sub>2</sub> act in combination to stimulate the proliferative potential of leiomyoma cells through the induction of EGF and EGF-R expression. We also found that Bcl-2 protein, an apoptosis-inhibiting gene product, was abundantly expressed in leiomyoma relative to that in normal myometrium and that Bcl-2 protein expression in leiomyoma cells was upregulated by P<sub>4</sub>, but downregulated by E<sub>2</sub>. It seems, therefore, likely that P<sub>4</sub> may also participate in leiomyoma growth through the induction of Bcl-2 protein in leiomyoma cells. The abundant expression of Bcl-2 protein in leiomyoma cells may be one of the molecular bases for the enhanced growth of a leiomyoma relative to that of normal myometrium in the uterus.
Topically Applied Water Extract of Propolis to Suppress Corneal Neovascularization in Rabbits
Authors: Hepşen İbrahim F. , Er Hamdi , Çekiç Osman 
Published: April 2003

<i>Purpose:</i> Propolis, a natural honey bee hive product, has anti-inflammatory and antioxidative properties. We aimed to assess the possible contribution of topically applied propolis to the suppression of corneal neovascularization (CNV). <i>Methods:</i> The effect of a water extract of propolis (WEP) 1% drops (group 1) in comparison with dexamethasone 0.1% (group 2) and saline (group 3) on CNV was tested in rabbit corneas injured by silver nitrate cauterization. The extent of CNV was quantitated as the area of CNV and the percent area of CNV for each cornea of the three groups (12 right eyes per group) in the first week of the treatment. The mean percent CNV was used for statistical analysis. <i>Results:</i> The corneas treated with the topical WEP 1% had an almost equal percent CNV as compared with the corneas treated with topical dexamethasone 0.1% and had less percent CNV than the control eyes. The quantitative analysis in groups 1, 2 and 3 revealed that the mean percent CNV was 41.0 ± 14.1, 39.4 ± 11.0 and 56.9 ± 18.4, respectively. The differences between both groups 1 and 3 as well as groups 2 and 3 were statistically significant (p = 0.02 and p = 0.01, respectively), whereas the difference between groups 1 and 2 was not significant (p = 0.86). <i>Conclusions:</i> The topical application of a WEP 1% has an inhibitory effect on CNV in the rabbit’s cornea. The inhibitory effect of propolis was shown to be comparable to that of topical dexamethasone 0.1%, a potent inhibitor of angiogenesis. We suggest that the effect of propolis may partially be due to its inhibitory effect on the activity of both cyclo-oxygenase and lipo-oxygenase.
Ofloxacin Levels after Intravitreal Injection
Authors: Öztürk Faruk , Kortunay Selim , Kurt Emin , Inan Ü. Übeyt , İlker S. Sami , Bascı Nursabah E. , Bozkurt Atila , Kayaalp S. Oǧuz 
Published: April 2003

<i>Purpose:</i> This study was carried out to get an insight into the ofloxacin elimination after intravitreal injection in rabbits. We also studied the effects of trauma and inflammation on the vitreous ofloxacin levels after intravitreal injection of ofloxacin. <i>Methods:</i> A penetrating eye injury in the right eye was inflicted on 24 rabbits and another 12 animals were used as control. A standardized intraocular inflammation was induced by intravitreal injection of a suspension of <i>Staphylococcus aureus</i> in half of the traumatized eyes. Ofloxacin (200 µg/0.1 ml) was injected into the midvitreous cavity of both traumatized and control right eyes, and samples were obtained at 2, 8, 24 and 48 h after injection. Drug concentrations were measured using high-pressure liquid chromatography analysis. <i>Results:</i> Vitreous levels of ofloxacin were above the MIC<sub>90</sub> at 2 and 8 h in all groups for most of the common microorganisms causing endophthalmitis and also at 24 h in traumatized-infected eyes. At the second hour, the mean vitreous concentrations of ofloxacin both in traumatized and traumatized-infected eyes were lower than that in the control eyes (p < 0.05). At 8 h, the mean vitreous concentrations of ofloxacin in the traumatized and in the traumatized-infected eyes were higher than that in the control eyes (p < 0.05). At 24 h, the mean ofloxacin concentration was higher in the traumatized-infected eyes than that in control (p < 0.01) and traumatized eyes (p < 0.05), and also higher in the traumatized eyes than that in the control eyes (p < 0.05). The mean ofloxacin concentrations in the traumatized and traumatized-infected eyes were significantly higher (p < 0.01) than those in the controls at 48 h. The elimination half-life of ofloxacin in the control eyes was 5.65 h and trauma and inflammation prolonged the half-life to 9.47 and 9.72 h, respectively. <i>Conclusion:</i> Clearance of ofloxacin is fast and appears to be reduced by trauma and inflammation. Therapeutic drug levels in traumatized-infected eyes were maintained up to 24 h. This may be an important pharmacokinetic advantage in treating endophthalmitis unless the dose used has local toxicity and allows a longer dose interval when the dose is repeated.
Increased Cell Surface Expression of Receptors for Transforming Growth Factor-β on Osteoblasts from Patients with Osteogenesis imperfecta
Authors: Gebken J. , Brenner R. , Feydt A. , Notbohm H. , Brinckmann J. , Müller P.K. , Bätge B. 
Published: April 2003

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder usually characterized by either a reduction in the production of normal collagen I or the synthesis of abnormal collagen. The variability in the clinical phenotype is not in each case sufficiently explained by the underlying mutation in the collagen I genes. Also, biochemical differences between mutant collagen from different tissues suggest additional regulatory mechanisms possibly involved in matrix deposition and maturation, two processes in which transforming growth factor-β (TGF-β) plays an important role. We, therefore, studied the cell surface expression and functional properties of TGF-β receptors I, II and III on osteoblasts from a group of OI patients compared to healthy controls. Receptor number and affinity were determined by Scatchard analysis of binding data and TGF-β receptor II gene expression was assessed by RT-PCR. Ligand-induced downregulation of TGF-β receptors was analyzed to demonstrate the dynamic response to exogenous stimuli. All experiments were performed in parallel in human osteoblastic cells from OI patients and from age-matched controls. TGF-β receptors I, II and III (betaglycan) were present on osteoblasts from both healthy donors and OI patients. The receptor numbers were significantly higher (29,000 per cell) on OI osteoblasts than on age-matched control osteoblasts (12,000 per cell) in spite of similar steady state levels for TGF-β receptor II mRNA in OI and control cells. Furthermore, receptor affinity was not significantly different in OI osteoblasts (181 vs. 177 n<i>M</i><sup>–1</sup>), and the receptor number did not depend on the culture substrate. With respect to dynamic adaption, ligand-induced downregulation of TGF-β receptors was reduced in OI osteoblasts. In conclusion, the human osteoblastic cells from patients with OI investigated all have an elevated number of cell surface receptors for TGF-β, without any evidence for a transcriptional regulation of TGF-β receptor II. On the functional level, there is some evidence for an impaired adaptive behavior of receptor presentation, whereas receptor affinity is unchanged.
Effect of Heat-Pretreatment on Interleukin-2-Activated Killer Cells for in vitro Purging
Authors: Tanaka M. , Honda J. , Imamura Y. , Shiraishi K. , Tanaka K. , Oizumi K. 
Published: April 2003

<i>Objective: </i>Lymphokine-activated killer activity is effective in purging residual malignant cells from autologous bone marrow (BM) or leukapheresis collections for peripheral blood progenitor cells (PBPC). In this study, the effect of additional heat pretreatment on IL-2-activated cytotoxicity was examined. <i>Methods:</i> Nonadherent mononuclear cells from peripheral blood (PB), PBPC collections or BM were exposed to the desired temperature for 1 h, and successively cultured for 7 days in the presence of 1,000 units/ml of recombinant human interleukin-2 (IL-2). Cytotoxicity of IL-2-activated cells was determined by flow cytometry, using PKH-26-labelled K-562 or Raji target cells, and the cell surface antigens were also analyzed. <i>Results: </i>IL-2-activated cells from all specimens showed a distinct generation of cytotoxic activities. The activities were significantly decreased by heat at 42°C, but not changed by heat pretreatment at 40°C. In the surface expression of IL-2-activated cells, the increase of CD56+ cells from PB, PBPC collections and the decrease of CD28 cells from PBPC collections were shown to be significant (p < 0.05), but these changes were not found when the cells were heat-pretreated at 42°C. <i>Discussion:</i> These results suggested that a tumor-killing therapeutic temperature (≧42°C) may lead to a disadvantage in posttransplantation immunity, and that this reduction of IL-2-activated cytotoxicity may partly be due to a lack of the enhancement of CD56+ cells or the reduction of CD28+ cells.
A Theoretical Model of Benign External Hydrocephalus That Predicts a Predisposition towards Extra-Axial Hemorrhage after Minor Head Trauma
Authors: Papasian Nora C. , Frim David M. 
Published: April 2003

<i>Introduction:</i> There is controversy over whether there exists a predisposition towards bleeding into the subdural space in infants with benign external hydrocephalus (BEH) or other enlargement of the extra-axial space (e.g. subdural hygroma). The presumed etiology implicates shear forces in over-stretching the extra-axial blood vessels. We have created a model of the intracranial space that approximates certain aspects of BEH. Using this model, we predict situations where children with BEH will bleed into the extra-axial space when normal infants will not. <i>Methods:</i> The cranial model consists of two spheres representing the brain and the skull. The distance between them represents the width of the extra-axial space. The spheres are concentric (with interspheric distance equal to N) in the normal condition and nonconcentric in BEH. In BEH, the distance between the two spheres varies from N to Q (0 < N ≤ Q) over a 906 M ≤ Q, with the translation orthogonal to the vector of N and parallel to that of M or vice versa), then the final length V<sub>f</sub> of a vein V is V<sub>f</sub> = (N<sup>2</sup> + M)<sup>1/2</sup>, and the stretch ratio V<sub>f</sub>/V<sub>i</sub> is: V<sub>f</sub>/V<sub>i</sub> = (N<sup>2</sup> + M<sup>2</sup>)<sup>1/2</sup>/N·S<sub>i</sub>, with S<sub>i</sub> the slack factor, where i represents either n for normal or b for BEH and M = N in the normal condition. <i>Results:</i> Given an equivalent capacity of veins to resist stretch injury (based on the proportion of change in length), for brain translations after a low-impact head injury, stretch ratios for BEH veins range from 1.677 to 3.436, whereas in the normal condition they range from 1.061 to 1.179. Therefore, for an increase in subarachnoid space from 3 (normal) to 6 mm (BEH), brain translocation in BEH will stretch veins beyond an average breaking point when the translation for the normal condition will not. <i>Conclusions:</i> Mathematical modeling of the cranial vault produces a relationship between venous stretch and the width of the extra-axial space. These equations predict an increased frequency of venous stretch injury in the situation of widened extra-axial space. Such venous injury is consistent with forces generated by minor trauma. This relationship, as predicted by our model, could underlie a predisposition towards extra-axial bleeding after minor head trauma in infants with BEH.
Telemetric Assessment of Intracranial Pressure Changes Consequent to Manipulations of the Codman-Medos Programmable Shunt Valve
Authors: Frim David. M. , Lathrop Dawn 
Published: April 2003

<i>Introduction:</i> Noninvasive manipulation of programmable shunt valves may allow customization of intracranial pressure (ICP) dynamics in individual shunted patients. Manipulations of the recently FDA-approved Codman-Medos variable pressure valve (VPV) are monitored by radiographic changes in the valve mechanism, necessitating a skull radiograph with each pressure change. We wished to assess the in vivo impact of VPV manipulations on ICP changes using a noninvasive telemonitor as an alternative to radiographic confirmation and as a method for validating the ICP changes. <i>Methods:</i> TeleSensor devices (Radionics) were implanted in-line with 12 VPV shunt systems. ICP was assessed telemetrically in the supine position whenever the valve pressure was adjusted (both before and 2–5 min after the manipulation). <i>Results:</i> Valve manipulation was confirmed by radiograph for the initial manipulations only and matched the telemetric pressure changes observed in all cases. Confirmed manipulations of the valve were generally followed by a near equivalent relative change in ICP (≤2 cm difference 74% of the time); however, the absolute value of the supine ICP was dependent on the entire shunting system and was equivalent to the valve setting only 11% of the time. Supine ICP and ICP dynamics were also dependent more on the shunt system than simply on the valve setting and were different for each of the shunt systems tested. <i>Conclusions:</i> We have confirmed that the VPV does cause ICP changes in shunted hydrocephalic patients that are essentially equivalent to programmed relative changes in the valve settings. These changes can be as easily monitored by noninvasive telemetry as by repeated radiography. However, our observations demonstrate that additional factors in the shunting system render the ICP absolutely equivalent to the VPV setting only rarely, implying that a programmable shunt valve is not necessarily equivalent to programmable ICP.
Pharmacological Properties of Fidarestat, a Potent Aldose Reductase Inhibitor, Clarified by Using Sorbitol in Human and Rat Erythrocytes
Authors: Sobajima Hiroshi , Aoki Takahiko , Sassa Hiromi , Suzuki Takeshi , Taniko Kaori , Makino Mitsuhiro , Mizuno Kuniharu , Suzuki Tsunemasa 
Published: April 2003

We examined the effect of fidarestat on the increase in sorbitol content in erythrocytes from healthy volunteers in vitro. Fidarestat inhibited the increase with an IC<sub>50</sub> value of 18 nmol/l. A subsequent experiment showed that fidarestat had a similar inhibitory effect on the increase in sorbitol content in erythrocytes from diabetic patients. On the other hand, epalrestat, the only aldose reductase inhibitor used clinically, inhibited increase in sorbitol content at a concentration over 500-fold higher than fidarestat. Although the IC<sub>50</sub> value of fidarestat was not affected by fasting plasma glucose, HbA<sub>1C</sub>, age, aldose reductase content or gender, there was a significant positive relationship between the IC<sub>50</sub> value of epalrestat and fasting plasma glucose. In addition, in fidarestat (0.25–2 mg/kg)-treated diabetic rats, the inhibitory rate for erythrocyte sorbitol accumulation was well correlated with that for nerve sorbitol accumulation, which indicates that erythrocyte sorbitol is available for assessing the state of sorbitol pathway flux in target tissue after fidarestat administration. These results suggest that fidarestat potently inhibits the increase in sorbitol pathway flux in diabetic patients independent of various factors and that erythrocyte sorbitol is useful for its estimation.