bluuebunny/crossref_metadata_2025 huggingface dataset:
Ebselen attenuates oxidative stress‐induced apoptosis via the inhibition of the c‐Jun N‐terminal kinase and activator protein‐1 signalling pathway in PC12 cells
Authors: Yoshizumi Masanori , Kogame Toshiaki , Suzaki Yuki , Fujita Yoshiko , Kyaw Moe , Kirima Kazuyoshi , Ishizawa Keisuke , Tsuchiya Koichiro , Kagami Shoji , Tamaki Toshiaki
Published: September 2002

Ebselen (2‐phenyl‐1,2‐benzisoselenazol‐3[2H]‐one) is a selenoorganic compound exhibiting both glutathione peroxidase activity and antioxidant activity. Although it has been reported that ebselen is effective for oxidative stress‐induced neuronal damage both in vivo and clinically, the precise mechanisms of the efficacy have not yet been elucidated. Thus, we hypothesized that ebselen may affect reactive oxygen species‐induced mitogen‐activated protein (MAP) kinase activation in cultured PC12 cells.

Our findings showed that hydrogen peroxide (H2O2) stimulated rapid and significant activation of extracellular signal‐regulated kinase (ERK)1/2, c‐Jun N‐terminal kinase (JNK) and p38 in PC12 cells, which is a model of catecholamine‐containing neurons.

H2O2‐induced JNK activation was inhibited by ebselen, whereas ERK1/2 and p38 activation by H2O2 were not affected by ebselen.

Inhibition by ebselen of H2O2‐induced hydroxyl radical generation in PC12 cells was observed using electron paramagnetic resonance measurements. Ebselen also inhibited H2O2‐induced increases in DNA binding activity of activator protein‐1 (AP‐1), a downstream transcription factor of JNK, composed of the c‐Jun homo/heterodimer.

Finally, pretreatment of cells with ebselen resulted in a significant recovery from cell death including apoptosis by H2O2 in PC12 cells.

These findings suggest that ebselen attenuates oxidative stress‐induced neuronal cell death through the inhibition of the JNK and AP‐1 signalling pathway. Thus, inhibition of JNK by ebselen may imply its usefulness for treatment of ischaemic cerebral diseases relevant to neuronal cell death.

British Journal of Pharmacology (2002) 136, 1023–1032. doi:10.1038/sj.bjp.0704808
Induction of mitochondrial permeability transition by auranofin, a Gold(I)‐phosphine derivative
Authors: Rigobello Maria Pia , Scutari Guido , Boscolo Rita , Bindoli Alberto
Published: September 2002

Gold(I)‐thiolate drugs are compounds that specifically interact with thiol and/or selenol groups and are essentially utilized in the treatment of rheumatoid arthritis.

Considering the importance of thiol groups in regulating mitochondrial membrane permeability, the effects of auranofin (S‐triethylphosphinegold(I)‐2,3,4,6‐tetra‐O‐acetyl‐1‐thio‐β‐D‐glucopyranoside), a second‐generation gold drug, were studied on mitochondria isolated from rat liver.

Auranofin, at submicromolar concentrations, was able to induce the mitochondrial membrane permeability transition observed as swelling and loss of membrane potential. Both events are completely inhibited by cyclosporin A, the specific inhibitor of mitochondrial permeability transition. Calcium ions and energization by succinate are required for the occurrence of permeability transition.

By interacting with the active site selenol group, auranofin results as an extremely potent inhibitor of mitochondrial thioredoxin reductase, both isolated and in its mitochondrial environment.

It is concluded that auranofin, in the presence of calcium ions, is a highly efficient inducer of mitochondrial membrane permeability transition, potentially referable to its inhibition of mitochondrial thioredoxin reductase.

British Journal of Pharmacology (2002) 136, 1162–1168. doi:10.1038/sj.bjp.0704823
Rapid neuromodulation by cortisol in the rat paraventricular nucleus: an in vitro study
Authors: Zaki Abu , Barrett‐Jolley R
Published: September 2002

We have used a range of in vitro electrophysiological techniques to investigate the mechanism of rapid cortisol neuromodulation of parvocellular neurones in the rat paraventricular nucleus.

In our study, we found that cortisol (10 μM) increased spontaneous action–current firing frequency to 193%. This effect was insensitive to the glucocorticoid intracellular‐receptor antagonist mifepristone.

Cortisol (0.1–10 μM) had no detectable effects on whole‐cell GABA current amplitudes, or GABAA single‐channel kinetics.

Cortisol (10 μM) inhibited whole‐cell potassium currents in parvocellular neurones by shifting the steady‐state activation curve by 14 mV to the right.

Additionally, in a cell line expressing both the glucocorticoid intracellular receptor and recombinant, fast inactivating potassium channels (hKv1.3), cortisol (1 and 10 μM) inhibited potassium currents by shifting their steady‐state activation curves to the right by 12 mV (10 μM cortisol). This effect was also insensitive to the cortisol antagonist, mifepristone.

These data suggest that inhibition of voltage‐gated potassium channels may contribute to the rapid neuromodulatory effects of cortisol, possibly by direct interaction with the ion channel itself.

British Journal of Pharmacology (2002) 137, 87–97. doi:10.1038/sj.bjp.0704832
Monoclonal gammopathy in Iceland: a population‐based registry and follow‐up
Authors: Ögmundsdóttir Helga M. , Haraldsdóttir Vilhelmína , M. Jóhannesson Guðmundur , Ólafsdóttir Guðríður , Bjarnadóttir Kristín , Sigvaldason Helgi , Tulinius Hrafn
Published: September 2002

Summary. The term monoclonal gammopathy (MG) signifies the benign or malignant clonal growth of B lymphocytes. In the present study, monoclonal gammopathy of unknown significance (MGUS) was defined as those patients with no identified haematological malignancy. A database was constructed of all 713 MG patients in Iceland between 1976 and 1997 and compared with the Icelandic Cancer Registry. The age‐standardized incidence per 100 000 of MG was 10·3 for males and 8·6 for females, calculated for the whole period, rising steadily from 5·8 (men) and 4·9 (women) during the 5‐year period 1976–80 to 14·7 (men) and 12·5 (women) during the last 5 year period. Age‐standardized incidence rates were very low for subjects under 50 years of age, then increased with age from 11 and 17 per 100 000 at 50‐54, to 169 and 119 per 100 000 at age 80–84, for men and women respectively. No association was detected between MG and non‐haematological malignancies, neither retrospectively nor prospectively. Haematological malignancy was diagnosed in 209 (29·3%) cases before the recorded finding of MG or within the same calendar year, leaving 504 (70·7%) patients diagnosed with MGUS. Of these, 51 (10%) progressed to multiple myeloma or Waldenström's macroglobulinaemia after a mean interval of 3·8 years; mean follow‐up was 7·4 years, median 6 years. The most common immunoglobulin (Ig) class was IgG (55%), followed by IgM (32%) and IgA (13%). MGUS was a highly significant risk factor for developing haematological malignancies and the risk was significantly greater for MG of the IgA class compared with either IgG or IgM.
Interleukin‐12 and Perforin mRNA Expression is Augmented in Blood Mononuclear Cells in Multiple Sclerosis
Authors: Matusevicius  , Kivisäkk  , Navikas  , Söderström  , Fredrikson  , Link
Published: September 2002

Cytokines are suggested to orchestrate an abnormal immune response in multiple sclerosis (MS). The regulatory cytokine interleukin (IL)‐12 induces T‐helper (Th) cell switch to the Th1 type and the production by cytotoxic T cells of perforin, a cell lysis‐inducing factor. It has been suggested that Th1‐like cytokines may promote the development of MS, and the production of perforin to induce oligodendrocyte damage. In‐situ hybridization with radiolabelled synthetic oligonucleotide probes was used to detect and enumerate mononuclear cells (MNC) expressing IL‐12 and perforin mRNA in blood and cerebrospinal fluid (CSF) from patients with MS and controls. Plasma and CSF levels of IL‐12 (p70) were evaluated by ELISA. Higher numbers of IL‐12 and perforin mRNA‐expressing MNC were registered in blood in MS and also in controls with aseptic meningoencephalitis (AM) compared to healthy subjects. There were a few patients with other non‐inflammatory neurological diseases who also had high levels of IL‐12 or perforin mRNA expressing blood MNC. A parallel elevation was observed for IL‐12 (p70) concentrations in plasma. In the MS patients' CSF, there was a further augmentation of IL‐12 mRNA expressing MNC. To evaluate autoantigen‐induced IL‐12 and perforin mRNA expression, blood MNC were cultivated ± myelin basic protein (MBP), a candidate autoantigen in MS. Higher numbers of MBP‐reactive IL‐12 and perforin mRNA expressing blood MNC were detected in MS than controls. The augmentation of both IL‐12 and perforin in MS might reflect ongoing inflammatory processes in MS and could represent targets for future treatments.
Dismantling in Cell Death: Molecular Mechanisms and Relationship to Caspase Activation
Authors: Depraetere  , Golstein
Published: September 2002

The notion of a cell death programme was introduced in view of the reproducibility of its occurrence in time and space (e.g. in the developing embryo) and of its genetic determination. Programmed cell death can be schematically subdivided into three steps: a signalling phase, an execution phase and a dismantling phase. This review focuses on the latter. Apoptosis is the most studied form of dismantling of animal cells. The molecular pathways leading to certain apoptotic lesions appear to be dependent on the proteolytic activity of caspases. Death itself can, however, be caspase‐independent. Also, non‐apoptotic forms of cell death exist, even in animal cells; their molecular bases are still unknown. The relationship between cell death, apoptosis and caspases is discussed.
Detection of the actin scavenger system in burn wound fluid
Authors: Grinnell Frederick , Baxter Charles R. , Zhu Meifang , Yin Helen L.
Published: September 2002

The intravascular actin scavenger system depolymerizes and sequesters actin released after tissue injury. Studies were carried out to determine if this system is active in the extracellular space during wound repair. Using burn wound fluid as a noninvasive means for analyzing the wound environment, we measured actin accumulation and actin complex formation with the plasma proteins responsible for scavenger function. Actin at concentrations as high as 0.25 mg/ml (∼5 µmol/L) was found in burn wound fluid samples from 9 of 11 patients. Wound fluid also contained the two plasma proteins that bind actin—gelsolin (both plasma and cytoplasmic forms) and Gc protein. Because actin in wound fluid was complexed with gelsolin and Gc protein, we conclude that the components of the actin scavenger system are functional in wound tissue. In addition, proteolysis of gelsolin, but not actin or Gc protein, appeared to occur at the wound site. Gelsolin proteolysis was accompanied by the appearance of 49 kd gelsolin fragments, and wound fluid samples lacking intact gelsolin also contained high metalloproteinase levels.
Evaluation of the wound healing potential in human beings from the subcutaneous insertion of expanded polytetrafluoroethylene tubes
Authors: Jorgensen Lars N. , Kallehave Finn , Karlsmark Tonny , Vejlsgaard Gunhild L. , Gottrup Finn
Published: September 2002

Subcutaneous insertion of expanded polytetrafluoroethylene tubes with local anesthesia constitutes a minimally invasive model permitting quantitative and qualitative studies of the wound healing potential in human beings. Light and electron microscopic examination of these implants in rats showed a normally appearing granulation tissue. The amount of hydroxyproline accumulated in the expanded polytetrafluoroethylene tubes may be assayed and converted to collagen content. In 28 surgical patients, the collagen content increased from 6.6 µg/cm (interquartile range: 5.1 to 9.9) after 5 days to 12.4 µg/cm (7.1 to 16.8) after 10 days (p < 0.05). The median ratio between the higher and lower collagen amount measured in two expanded polytetrafluoroethylene tubes inserted for an identical period within the same patient was 1.25 (1.10 to 1.81). This variability ratio was not related to the amount of collagen accumulated or the duration of implantation. There was a tendency for higher collagen amounts in the middle section than in the ends of the expanded polytetrafluoroethylene tubes, with a median ratio between the two sections equaling 1.12 (0.96 to 1.58); (p > 0.05). No infectious or hemorrhagic complications from the insertion occurred in any of the patients. Increments of collagen deposition with time may be easily assessed by this expanded polytetrafluoroethylene tube model, which is inexpensive and has high patient acceptance. Measurement variability was encountered, which has to be taken into account when designing clinical trials.
Effect of oxygen treatment and dressing oxygen permeability on wound healing
Authors: Pandit Abhay S. , Feldman Dale S.
Published: September 2002

Although it has been shown that both the level of tissue oxygen and its gradient are critical factors in the healing process, optimal conditions for oxygen therapy have not been determined. In this study, both the oxygen level and oxygen gradient for a full‐thickness defect were modified on the basis of preceding in vitro studies to determine the effect on the healing process. The goal of this study was to help determine the optimal clinical oxygen treatment protocol. Specifically, the healing of full‐thickness defects in a rabbit model as determined by histomorphometric analyses (cell and tissue volume fraction, epithelialization, and contraction) under two types of dressings with or without oxygen treatment (70% O2) was investigated. One of the dressings was more oxygen permeable than the other. No significant differences were found in the histomorphometric response between the wounds covered with the oxygen‐permeable and oxygen‐impermeable dressings in the group without supplemental oxygen. Oxygen treatment, however, seemed to enhance the healing response significantly. According to the histomorphometric response, the wounds covered with the oxygen‐impermeable dressings were significantly better than those with the oxygen‐permeable dressing in the oxygen‐treated group after 1 week, but the wounds covered by the oxygen‐permeable dressings were better healed at 3 weeks. Therefore, oxygen‐impermeable dressings may be useful only in the early stages of healing, before granulation tissue formation.
In vivo characterization of interleukin‐4 as a potential wound healing agent
Authors: Kucukcelebi Ahmet , Harries Richard H. C. , Hennessey Patrick J. , Phillips Linda G. , Broemeling Lyle D. , Listengarten Dmitry , Ko Francis , Narula Satwant , Robson Martin C.
Published: September 2002

Interleukin‐4 increases the synthesis of extracellular matrix proteins, including types I and III collagen and fibronectin, by both human and rat fibroblasts. Because fibroblasts are the final common effector cells of most phases of tissue repair, this study set out to investigate the effects of interleukin‐4 on the healing of three different types of wounds. Acute excisional and chronic granulating wounds inoculated with Escherichia coli and incisional wounds in streptozotocin‐induced diabetic Sprague‐Dawley rats were used. Recombinant murine or human interleukin‐4 was applied topically to the open wounds at doses of 0.1, 1.0, or 10.0 µg/cm2/wound for 5 or 10 days. Incisional wounds received the same doses once—at the time of wounding. The time taken to achieve wound closure or wound breaking strength measurements of wounds was recorded and compared with relevant untreated control groups. Wound contraction was impaired in the presence of bacteria, and this was reversed by all doses of recombinant murine interleukin‐4. Recombinant murine interleukin‐4 had no effect on the wound closure of noncontaminated wounds; it reduced wound breaking strength in acute excisional wounds, except in a contaminated setting when wounds were treated with 1.0 pg/cm2/wound. Recombinant interleukin‐4 (1.0 µg) improved breaking strength of both diabetic and normal incisional wounds. The apparent pleiotropic effect of interleukin‐4 on wound breaking strength under different wound conditions may be related not only to the activity of the fibroblast but also the ratio of cross‐linked collagen/total collagen content of wounds. This study suggests that interleukin‐4 may be a useful agent for accelerating closure of wounds, particularly where healing is impaired.
Expression of interleukin‐6 and tumor necrosis factor in peritoneal mononuclear cells after gastrectomy
Authors: Fujita Itsuo , Onda Masahiko , Tokunaga Akira
Published: September 2002

As macrophages are found in peritoneal exudates after abdominal surgery, interleukin‐6 and tumor necrosis factor‐α, their messenger RNAs and immune‐specific proteins would also be expected to be found in both peritoneal fluid and mononuclear cells under such conditions. The peritoneal fluid and plasma of patients who had undergone gastrectomy were investigated on postoperative days 1, 3, 5, and 7. Evidence of mRNA expression and the intracellular immunocytochemical localization of interleukin‐6 and tumor necrosis factor‐α was determined in cells isolated from peritoneal fluid, and immune‐specific protein levels in the peritoneal fluid were measured. Both interleukin‐6 and tumor necrosis factor‐α proteins were identified immunocytochemically in the cytoplasm of peritoneal mononuclear cells, and their mRNAs were detected by the reverse transcriptase‐polymerase chain reaction. The concentration of interleukin‐6 in the peritoneal fluid was significantly higher than that in the plasma, and a high level of tumor necrosis factor‐α was found in the peritoneal fluid, despite its absence from plasma. Expression and changing levels of interleukin‐6 and tumor necrosis factor‐α in human peritoneal fluid after gastrectomy were shown, indicating local production of these cytokines, which may play important roles in tissue repair.
Pancreatic islet transplantation prevents the impaired healing of intestinal anastomoses in Lewis rats with streptozotocin‐induced diabetes
Authors: Verhofstad Michiel H. J. , Van der Hem Lieuwe G. , Van der Vliet J. Adam , Hendriks Thijs
Published: September 2002

Pancreatic islet transplantation may prevent secondary complications of diabetes mellitus, but its potential benefits on early complications have been incompletely examined. The objective of this study was to investigate whether preoperative islet transplantation would normalize impaired healing of intestinal anastomoses in diabetic rats. Male Lewis rats were divided into a control group (I), an uncontrolled diabetic group (II), and a transplant group (III). Nine days before surgery, groups II and III were rendered diabetic by injection of streptozotocin. Two days before surgery, group III received an intrahepatic isogenic two‐donor islet graft, whereas groups I and II underwent sham transplantation. On day 0, all animals underwent resection and anastomosis of both ileum and colon. Half of the animals in each group were killed on day 3 and the other half were killed on day 7. Blood glucose levels in group II rats remained over 20 mmol/L throughout the experiment, whereas in group III rats they were normalized within 24 hours after transplantation. At death, group II rats, but not groups I and III rats, showed a high incidence of anastomotic abscesses. Uncontrolled diabetes lowered anastomotic strength, and transplantation prevented this reduction. For instance, anastomotic bursting pressure in the ileum on day 3 was 11.9 ± 4.8 kPa in group I rats, 3.3 ± 3.0 kPa in group II rats, and 11.1 ± 4.3 kPa in group III rats. Rupture on day 3 always occurred within the anastomosis, whereas on day 7 intraanastomotic ruptures were only observed in group II rats. No differences between the groups were found for either anastomotic hydroxyproline concentration or content. However, the acid solubility of anastomotic collagen was significantly higher in group II rats than in groups I and III rats. Thus, uncontrolled diabetes lowers anastomotic strength without affecting anastomotic collagen content. Defective repair is prevented by pancreatic islet transplantation before surgery.
Localization of platelet‐derived growth factor receptor subunit expression in chronic venous leg ulcers
Authors: Peus Dominik , Jungtäubl Helmut , Knaub Sigurd , Leuker Andreas , Gerecht Klaus , Ostendorf Rolf , Meyer‐Ingold Wolfgang , Wlaschek Meinhard , Krieg Thomas , Ruzicka Thomas , Scharffetter‐Kochanek Karin
Published: September 2002

Cellular responses to platelet‐derived growth factor, which affects all phases of the wound healing process, are dependent on the interaction of the growth factor with its cell surface receptors. Recently, we have shown that the platelet‐derived growth factor‐receptor was not expressed in uninjured human skin. In acute human wounds healing by secondary intention, both platelet‐derived growth factor‐receptor subunits were coordinately expressed, whereas no expression was found after reepithelialization at day 47. Even though impaired wound healing may be due to uncoordinated expression or the failure to express platelet‐derived growth factor‐receptor subunits, little is known regarding their expression in chronic ulcers. We studied the localization of platelet‐derived growth factor‐receptor expression in chronic venous leg ulcers of 15 patients with a median age of 73 years. Cryostat sections of biopsy specimens were immunostained with the use of antibodies against the α‐ and the β‐platelet‐derived growth factor subunits. RNA was extracted from biopsy specimens and subjected to Northern blot analysis with the use of oligolabeled complementary DNA for the platelet‐derived growth factor‐receptor. Platelet‐derived growth factor‐receptor α‐ and β‐subunit expression was found in fibroblast‐like cells within the wound bed and in cells beneath the epidermis of the wound edge. Platelet‐derived growth factor‐receptor β‐subunit expression was detected in endothelial cells of the vessels, in the granulation tissue, and the wound edge, whereas platelet‐derived growth factor‐receptor α‐subunit was not expressed in endothelial cells of the uninjured skin. This finding suggests that the platelet‐derived growth factor α‐subunit may be involved in vessel formation during tissue repair. Both platelet‐derived growth factor‐receptor subunits were expressed at the messenger RNA level indicating that the synthesis is at least partly regulated at a pretranslational level. As the cellular responsiveness to growth factors depends on their specific receptors, our finding that both platelet‐derived growth factor‐receptor subunits are expressed in chronic venous ulcers substantiates the concept of therapeutic trials with recombinant platelet‐derived growth factor.
Involvement of proteolytic enzymes—plasminogen activators and matrix metalloproteinases—in the pathophysiology of pressure ulcers
Authors: Rogers Alan A. , Burnett Stuart , Moore Joan C. , Shakespeare Peter G. , John Chen W. Y.
Published: September 2002

The role of matrix‐degrading enzymes, particularly plasminogen activators and matrix metalloproteinases, in the acute wound healing response has been the focus of many scientific studies. Only recently have these classes of endogenously produced proteinases been studied with regard to their involvement in the chronic wound environment. Using both in situ histologic zymography and immunohistochemical techniques, we examined the distribution of plasminogen activators and matrix metalloproteinase in the granulation tissue of pressure ulcers. Using in situ histologic zymography, urokinase was found to be the predominant plasminogen activator activity in the chronic wound granulation tissue, with little or no tissue‐type plasminogen activator activity. These results were confirmed with the use of immunohistochemical techniques. In contrast, tissue‐type plasminogen activator was found to be constitutively expressed in normal skin. Levels of matrix metalloproteinases were also found to be elevated in the granulation tissue of pressure ulcers. Immunohistochemical localization of leukocyte‐associated proteinases (PMN elastase and cathepsin G) suggested a highly inflamed environment within the pressure ulcer granulation tissue. These results suggest a highly proteolytic environment within the chronic wound.
Effects of insulin‐like growth factor‐I and insulin‐like growth factor binding protein‐1 on wound healing in a dermal ulcer model
Authors: Zhao Lily L. , Galiano Robert D. , Cox George N. , Roth Sanford I. , Mustoe Thomas A.
Published: September 2002

The effects on wound healing of insulin‐like growth factor‐I with and without insulin‐like growth factor binding protein‐1 were studied in a rabbit ear dermal ulcer model under both nonischemic and ischemic conditions. Wounds 6 mm in diameter were made on the ventral surface of rabbit ears for a total of 272 wounds in the nonischemic group and 77 wounds in the ischemic group. Insulin‐like growth factor‐I in varying doses (1 to 43 µg) and in combination with varying molar ratios of the binding protein were added at time of wounding to each wound. Wounds were analyzed histomorphometrically on day 7 after wounding. We found that insulin‐like growth factor‐I or binding protein alone at varying doses did not have any effects on wound healing parameters. Low to moderate doses (1 µg and 4 µg, respectively) of the combination of insulin‐like growth factor‐I with the binding protein in a molar ratio of 5:1 or 11:1 showed a 52% increase (p < 0.05) in new granulation tissue in the nonischemic model compared with controls but did not significantly augment new granulation tissue formation in the ischemic wound model. A high dose (43 µg) at a 10:1 molar ratio of growth factor to binding protein was required to elicit significantly enhanced wound healing in ischemic wounds. These results indicate that insulin‐like growth factor binding protein‐1 modulates the effects of insulin‐like growth factor‐I in promoting wound healing in vivo and that the combination is a highly effective vulnerary compound with effects comparable in magnitude with other growth factors previously tested in this model.
Bone regrowth after digit tip amputation in mice is equivalent in adults and neonates
Authors: Neufeld Daniel A. , Zhao Weiguang
Published: September 2002

Despite clinical and experimental reports of digit tip regrowth, bone regrowth after amputation through terminal phalanges has not been methodically documented. We have examined bone regrowth in mice after amputation through the terminal phalanx to determine how the level of amputation affects the response and whether the response varies between adults and neonates. Digit tips were amputated, and, at selected intervals greater than 5 weeks after amputation, digits were photographed and processed for whole mount staining with alizarin red stain. Amputations within the distal 40% of the terminal phalanx yielded grossly normal digits within 5 weeks and bone regrowth which usually attained or surpassed the original length. Amputations through the proximal 20% of the distal phalanx precluded nail plate regrowth, and bone grew minimally or regressed. Amputation through the intermediate 40% of the distal phalanx produced digit tips in which bone regrowth was correlated with nail regrowth and in which bone regrowth did not reach original levels. The response in adults and neonates was similar. The correlation between nail regrowth and bone regrowth may help to predict phalangeal bone regrowth after amputation in adults and juveniles.
Effect of electrical stimulation waveform on healing of ulcers in human beings with spinal cord injury
Authors: Baker Lucinda L. , Rubayi Salah , Villar Fernando , Demuth Sharon K.
Published: September 2002

Various electrical stimulation waveforms have been used to enhance wound healing, with little consideration for potential differences in their physiologic effect. The present study evaluated the effect of stimulation waveform and electrode placement on wound healing. Eighty patients with spinal cord injury and one or more pressure ulcers were treated. A total of 185 ulcers received 45 minutes of stimulation daily. Each ulcer was subjected to one of four treatment protocols: asymmetric biphasic waveform, symmetric biphasic waveform, microcurrent stim‐ulation, or a sham control protocol. Electrodes were placed outside the wounds, over intact skin and surrounding the area of the ulcer. Data were categorized by ulcers which healed during the protocol and those which did not. Analysis of the “good response” ulcers (n = 104) showed significantly better healing rates for those receiving stimulation with the asymmetric biphasic waveform, compared with the control and microcurrent groups. Mean healing rates from the present study were similar to previously reported measures. The waveforms studied possessed minimal polar capabilities, and the electrodes were placed outside the wound. These data show that electrical stimulation clearly enhanced healing of pressure ulcers in a significant number of individuals with spinal cord injury; the physiologic implications of these findings relative to the mechanism(s) by which electrical stimulation enhances wound healing are discussed. However, extrapolation of these results to patients with other types of wounds must await further study.
Transcutaneous oxygen measurements predict healing of leg wounds with hyperbaric therapy
Authors: Smith Bruce M. , Desvigne Lisa D. , Slade J. Benjamin , Dooley James W. , Warren Douglas C.
Published: September 2002

Twenty‐six patients with chronic leg wounds had transcutaneous oxygen measurements taken from the peri‐wound area and a chest reference site before undergoing hyperbaric oxygen therapy in order to evaluate the utility of transcutaneous oxygen measurements in predicting the response of wounds to hyperbaric therapy. Wound scores and wound areas were determined before treatment and after 10 hyperbaric exposures. Patients whose wounds averaged a 5% or greater reduction in wound score per treatment were designated “responders.” Nine patients' wounds exhibited at least a 5% reduction in wound score per treatment. There were no differences observed between responders and the 17 nonresponders in age, duration of the wound, initial wound area, initial wound score, or in wound or reference transcutaneous oxygen measurements. Responders required significantly fewer treatments to achieve wound closure than did nonresponders. Peri‐wound transcutaneous oxygen pressure when the patient was exposed to 2.4 atmospheres absolute correlated directly with the improvement in wound score per treatment (r = 0.64, p = 0.03). An inverse correlation was noted between surface peri‐wound transcutaneous oxygen pressure and improvement in wound score per treatment (r = −0.74, p = 0.006). Elevated peri‐wound transcutaneous oxygen measurements at 2.4 atmospheres absolute and reduced peri‐wound oxygen measurements at 1 atmosphere absolute were associated with a more rapid response to hyperbaric oxygen treatments in patients with chronic leg wounds. The use of these measurements should allow this expensive and time‐consuming therapy to be limited to those patients most likely to benefit.
Inhibition of wound closure by transforming growth factor‐β and dexamethasone in a fetal mouse limb organ culture model
Authors: Paul Ehrlich H. , Blewett Christopher , Krummel Thomas M. , Cutroneo Kenneth R.
Published: September 2002

Tissue repair comprises several physiologic processes including the deposition of a newly synthesized connective tissue matrix and the regeneration of the epidermis by reepithelialization. A fetal mouse limb organ culture system facilitates the investigation of both reepithelialization and connective tissue deposition in repair within a controlled environment. A sutured closed wound in an intact 18.5‐day old fetal mouse limb completely heals by 7 days. Including dexamethasone in the media inhibited both reepithelialization and connective tissue deposition. Concurrent administration of transforming growth factor‐β with dexamethasone restored the deposition of connective tissue but did not restore reepithelialization. When transforming growth factor‐β was given alone, connective tissue deposition was enhanced at both the wound site and in contiguous dermis, but reepithelialization did not proceed. Transforming growth factor‐β inhibited wound closure by blocking the migration of epidermal cells. The organ‐cultured, wounded fetal mouse limb system is sufficiently sensitive to show both mesenchymal cell‐enhancing activity as well as epithelial migration inhibiting activity by transforming growth factor‐β. The in vitro repair of fetal mouse limbs may serve as an in vitro system to test the influence of soluble agents on the repair process.
The role of growth factors in the healing of chronic wounds
Authors: Robson Martin C.
Published: September 2002

The clinical use of growth factors for the treatment of nonhealing human wounds holds great therapeutic potential. However, numerous clinical studies of recombinant growth factors used to treat chronic dermal wounds have generally reported disappointing results. Part of the explanation for these results may be a lack of appreciation of three basic principles related to the biology of wound healing and pharmaceutic considerations. Above all, the growth factor selected for a particular nonhealing wound must regulate a process of healing which is predominantly involved in healing that wound. A growth factor which stimulates epithelialization will be of little good in a wound which needs to heal by connective tissue deposition. Once the appropriate biologic modifier has been identified, one must be assured that there is a deficiency of that modifier in the wound environment. Finally, one must be sure that the delivery of the growth factor to the wound is in sufficient amount and duration to produce a biologic response. These considerations are exemplified with several clinical studies which did show improvement in the rate of healing of chronic wounds. Only when clinical trials are undertaken in which these tenets are incorporated in the study design will the true potential of various growth factors be appropriately determined.
Third-order Douglas–Kroll ab initio model potential for actinide elements
Authors: Paulovič Jozef , Nakajima Takahito , Hirao Kimihiko , Seijo Luis
Published: September 2002

A relativistic ab initio model potential (AIMP) method with the third-order Douglas–Kroll (DK3) approximation has been developed for the whole series of the actinide elements from Th to Lr. Two different cores, i.e., [Xe, 4f,5d] and [Xe, 4f], have been employed and the corresponding valence basis sets, (14s10p11d9f)/[6s5p5d4f] and (14s10p12d9f)/[6s5p6d4f], are presented for all actinides. The mean absolute errors of the AIMP relative to the all-electron results for the atomic SCF valence orbital energies (ε) and the radial expectation values (〈r〉) are 0.003 (0.001) hartree and 0.004 (0.006) bohr with the small (large) core set. The spectroscopic properties of the Σ+1 ground state of thorium monoxide, ThO, are calculated at the SCF and complete active space SCF levels. The DK3-AIMP results again satisfactorily reproduce the all-electron DK3 results. The large core set gives almost the same results as the small set for atomic and molecular calculations, suggesting that the 5d electrons can safely be omitted from the valence electrons in actinide chemistry.
Precise standard system for low dc magnetic field reproduction
Authors: Park P. G. , Kim Y. G. , Shifrin V. Ya. , Khorev V. N.
Published: September 2002

A standard system for low magnetic fields has been developed at the Korea Research Institute of Standards and Science. The system consists of a precision solenoid, He–Cs atomic magnetic resonance magnetometer, and apparatus for three-axis compensation of the Earth’s magnetic field. The variations of the Earth’s magnetic field are automatically compensated within 0.1 nT/h by a Cs atomic magnetic resonance field controller. The solenoid reproduces a dc field that is uniform at better than 3×10−7 within ±2 cm around the center. The experimentally measured coil constant and temperature coefficient of the solenoid are 1.231 0596×10−3 T/A (25 °C) and 3.8×10−7/°C, respectively. The standard serves for the calibration of magnetometers and uniform field coils, and also supports experiments related to research in magnetic fields in the range of (0.02–1.2) mT with (2–10)×10−6 uncertainty.
Critical behavior of drops in linear flows. I. Phenomenological theory for drop dynamics near critical stationary states
Authors: Bławzdziewicz Jerzy , Cristini Vittorio , Loewenberg Michael
Published: September 2002

The dynamics of viscous drops in linear creeping flows are investigated near the critical flow strength at which stationary drop shapes cease to exist. According to our theory the near-critical behavior of drops is dominated by a single slow mode evolving on a time scale that diverges at the critical point with exponent 1/2. The theory is based on the assumption that the system undergoes a saddle-node bifurcation. The predictions have been verified by numerical simulations for drops in axisymmetric straining flow and in two-dimensional flows with less vorticity than in shear flow. Application of our theory to the accurate determination of critical parameters is discussed.
On the nature of the low-field electromagneto-plastic effect
Authors: Pinchook A. I.
Published: September 2002

In the present study, reduction in the linear density of twinning dislocations resulting from the simultaneous application of high-density electric current pulses (40 A/mm2 for 400 μs) and constant magnetic field (with induction in 0.2 T) to bismuth crystals has been found. Current pulses and constant magnetic field were applied to the specimen after the deformation was introduced by a concentrated load and pileups of twinning dislocations were created. It has been clearly shown that the decrease in the linear density of twinning dislocations results in the elongation of the deformation twins. This effect occurs despite the increase of the number of twinning dislocations with an increase in the concentrated load. The experimental facts are in good accord with the modern concept of the electroplastic effect.
Charge-coupled device area x-ray detectors
Authors: Gruner Sol M. , Tate Mark W. , Eikenberry Eric F.
Published: September 2002

Charge-coupled device (CCD) area x-ray detector technology is reviewed. CCD detectors consist of a serial chain of signal components, such as phosphors, fiber optics or lenses, image intensifiers and the CCD which serve to convert the x-ray energy to light or electron-hole pairs and to record the spatially resolved image. The various combinations of components that have been used to make CCD detectors are described and the properties of each of the critical components are discussed. Calibration and correction procedures required for accurate data collection are described. The review closes with a brief description of future directions for solid-state area x-ray detectors.
Thermal instability of electrolytic capacitor bank used for gas puff valve
Authors: Bellan P. M.
Published: September 2002

It is shown that self-heating of electrolytic capacitors causes the output current of a capacitor bank to increase with successive shots even though the charge voltage is held constant. Self heating of only 10 °C can cause a near tripling in the gas output of the gas puffing valves commonly used in spheromak research. By using metallized polypropylene film capacitors instead of electrolytic capacitors the reproducibility is substantially improved (the shot-to-shot variation in gas output is reduced to be <0.5%).
70 keV neutral hydrogen beam injector with energy recovery for application in thermonuclear fusion research
Authors: Simonin A. , Armitano A. , Brugnetti R. , Cano V. , Dougnac H. , Fazilleau P.
Published: September 2002

A 70 keV 40 A hydrogen beam injector has been developed at Cadarache for a plasma diagnostic [motional Stark effect (MSE)] to provide a measurement of the plasma current distribution in the Tore–Supra tokamak. We present in this article the principle and the first experimental results of the injector, where a new type, and advantageous, energy recovery system, based on a magnetic neutralizer plasma confinement, has been developed. The hydrogen ion beam is accelerated to 70 keV with a three-grid multiaperture system (aperture diameter Φ=11 mm) with an ion current density of ≈160 mA/cm2. An ion source with a shape (height 1.2 m, width 80 mm) specifically adapted to the recovery system has been developed to meet the injector requirements: uniformity, high proton fraction (>80%), and high current density, ≈160 mA/cm2 over the whole extraction surface (900 cm2). A neutral (H0) beam power of 500 kW has been achieved with a divergence of ≈0.6° at 70 keV.
Energy levels and wave functions of vector bosons in a homogeneous magnetic field
Authors: Sogut K. , Havare A. , Acikgoz I.
Published: September 2002

We aimed to obtain the energy levels of massive spin-1 particles moving in a constant magnetic field. The method used here is completely algebraic. In the process to obtain the energy levels the wave function is expressed in terms of Laguerre polynomials.
Shapes of voltammogram spikes explained as resulting from the effects of finite electrode crystal sizes
Authors: Huckaby Dale A. , Medved’ Igor
Published: September 2002

We study the voltammogram spikes of the underpotential deposition at electrode surfaces that correspond to first-order phase transitions. The shape of symmetric spikes is approximated by the function cosh−2. In order to explain this spike shape microscopically, which is our main concern, we observe that an electrode surface consists of many small crystals. A voltammogram spike is then interpreted as an averaged result of the finite-size effects occurring in each of these crystals. This view also allows us to comment on asymmetry in the voltammogram spikes. Our analysis is based on the rigorous statistical mechanical techniques of the Pirogov–Sinai theory. For the sake of simplicity, we model the deposition process by the one-component lattice gas. We apply the results to the underpotential deposition of Cu on Pt(111) in a sulfuric acid medium, and find very good agreement with experiment.
Viscous flow reactor with quartz crystal microbalance for thin film growth by atomic layer deposition
Authors: Elam J. W. , Groner M. D. , George S. M.
Published: September 2002

A chemical reactor was constructed for growing thin films using atomic layer deposition (ALD) techniques. This reactor utilizes a viscous flow of inert carrier gas to transport the reactants to the sample substrates and to sweep the unused reactants and reaction products out of the reaction zone. A gas pulse switching method is employed for introducing the reactants. An in situ quartz crystal microbalance (QCM) in the reaction zone is used for monitoring the ALD film growth. By modifying a commercially available QCM housing and using polished QCM sensors, quantitative thickness measurements of the thin films grown by ALD are obtained in real time. The QCM is employed to characterize the performance of the viscous flow reactor during Al2O3 ALD.
Imaging of heavy-ion beams on kapton film
Authors: Bieniosek F. M. , Kwan J. W. , Prost L. , Seidl P. A.
Published: September 2002

Kapton film is used to image K+ ion beams in the 0.4 to 2 MeV energy range. Dose response is shown to be linear and to follow a simple model for a range of exposures. The measured profiles agree with profiles obtained with a slit scanner. Kapton has excellent spatial resolution, dynamic range, and discrimination against stray low energy and low mass particles.
Solvent-induced symmetry breaking of nitrate ion in aqueous clusters: A quantum-classical simulation study
Authors: González Lebrero Mariano C. , Bikiel Damián E. , Elola M. Dolores , Estrin Darı́o A. , Roitberg Adrian E.
Published: September 2002

A hybrid quantum-classical computational algorithm, which couples a density functional Hamiltonian to a classical bath, is applied to investigate symmetry breaking and the vibrational spectrum of [NO3]− in aqueous clusters. The nitrate ion was modeled using density functional theory with a Gaussian basis set; two different force fields for the classical bath were investigated: the TIP4P-FQ fluctuating charge and the TIP4P mean-field potentials. The choice of basis sets, functionals, and force field parameters has been validated by performing calculations on small complexes [NO3(H2O)n]− (n=1,2) at 0 K. We have found different asymmetrical configurations, mostly of Cs symmetry, with characteristic lifetimes in the picosecond range in a molecular dynamics (MD) simulation of [NO3 (H2O)124]− using the TIP4P potential. The vibrational density of states (DOS), computed by calculating the Fourier transform of the velocity autocorrelation function, shows two distinctive peaks corresponding to the antisymmetric N–O stretching (around 1500 cm−1) for each configuration, in contrast with the degenerate peak observed in the isolated solute. The DOS corresponding to the whole simulation, in which several configurations were visited, is similar to the broad band observed experimentally in aqueous solution. The structural and DOS results obtained for a TIP4P simulation of [NO3]− solvated with 256 water molecules do not differ significantly from those obtained with the smaller cluster, confirming that the main features of solvation are already present in the smaller system. In order to assess the influence of solvent polarization, we have performed a hybrid simulation employing the fluctuating charge TIP4P-FQ water potential. We obtain similar results to those obtained using the mean-field potential, except that residence times of each asymmetric configuration are larger than in the TIP4P case.
NO angular distributions in the photodissociation of (NO)2 at 213 nm: Deviations from axial recoil
Authors: Demyanenko A. V. , Potter A. B. , Dribinski V. , Reisler H.
Published: September 2002

Angular distributions of selected rotational states of NO(A 2Σ+,ν=0) products obtained in the 213 nm photodissociation of (NO)2 have been determined in a molecular beam by using the photofragment ion imaging technique. Specifically, images of NO(A,ν=0) products in N=0, 11, and 19 have been recorded, for which the maximum energies available to the NO(X 2Π) products are 2038, 1774, and 1278 cm−1, respectively. The recoil anisotropy parameter of the photofragments, βeff, decreases significantly at low center-of-mass translational energies from its maximum value of 1.36±0.05, and depends strongly on the rotational angular momentum of the photoproducts. This behavior is described well by a classical model that takes into account the transverse recoil component mandated by angular momentum conservation. For each of the observed NO(A) N states, highly rotating NO(X) levels are produced via planar dissociation, and the angular momenta are established at an interfragment separation of about 2.6 Å. For most of the center-of-mass translational energy range, both corotating and counterrotating fragments are produced, but at the lowest energies, only the latter are allowed. The correlated rotational energy distributions exhibit deviations from the behavior predicted by phase space theory, suggesting that exit-channel dynamics beyond the transition state influences the product state distributions. In this study, a new method for image reconstruction is employed, which gives accurate angular distributions throughout the image plane.