bluuebunny/crossref_metadata_2025 huggingface dataset:
Relationship Between Motility and Mitochondrial Functional Status in Canine Spermatozoa
Authors: Volpe S , Leoci R , Aiudi G , Lacalandra GM
Published: July 2009

Contents

Inner mitochondrial membrane potential (IMM) is considered a sensitive indicator for the energetic status and motility of spermatozoa. The relationship between sperm motility parameters evaluated by Computer Assisted Sperm motility Analyzer and plasma membrane integrity and IMM assessed by triple staining (PI/SYBR‐14 and JC‐1) was evaluated in 10 dogs of unknown fertility. Sperm motility showed large variations ranging from 10% to 98%. Proportion of viable sperm cells and of spermatozoa with high IMM ranged from 74% to 99% and from 53% to 87%, respectively. The presence of a high IMM assessed by JC‐1 was more strongly correlated to sperm viability (r = 1) than to sperm motility (r = 0.778). Our results indicate that JC‐1 is suitable for detection of IMM changes in canine spermatozoa, but it should always be associated with an objective motility analysis to avoid incorrect evaluation of potential sperm fertility. Ejaculates with a low motility rate showed an unexpectedly high proportion of sperm with high IMM, suggesting that mitochondrial respiration could not be sufficient to support sperm motility, although it may be important for sperm survival in the female genital tract.
Competency in laparoscopic colorectal surgery is achievable with appropriate training but takes time: a comparison of 300 elective resections with anastomosis
Authors: Dalton S. J. , Ghosh A. J. , Zafar N. , Riyad K. , Dixon A. R.
Published: July 2009

Aim  The aim of this retrospective cohort study was to compare outcomes in patients who underwent elective laparoscopic colorectal resection with anastomosis performed by a single surgeon or his training fellow.

Method  A prospective electronic database of all laparoscopic procedures between January 2005 and September 2008 was used. Two groups were compared; those patients operated upon by the Consultant trainer (C) and those by seven supervised Fellows (F). Fellows were either post CCT or in their last year of training. Three hundred consecutive patients undergoing laparoscopic colorectal resection with anastomosis were examined, 150 in each group. Groups were matched for indication, age, American Society of Anesthesiology (ASA) grade, cancer T stage and resection performed. Preoperative work‐up, operative surgery and anaesthesia were identical between groups.

Results  No significant difference was demonstrated in age, mean 67 (26–91) or ASA grade. Indications for surgery were; cancer (C) 120, (F) 126, diverticular disease (C) 22, (F) 20, Crohn’s disease (C) 8, (F) 7. Fellow’s mean operative time was significantly longer at 123 min (95%CI 117–134) compared to the consultant trainer −105 min. (95%CI 98–111): P < 0.01). No significant differences in the complication or conversion rates were demonstrated. Length of stay and the 30‐day readmission rates were similar.

Conclusion  In this retrospective cohort study we have demonstrate that when matched patients are compared, supervised trainee operating time is significantly longer than that of the consultant trainer but without any significant increase in length of stay, complication or readmission rates. Training to a level of competency takes time but not at the expense of patient care.
Effect of hair removal by Nd:YAG laser on the recurrence of pilonidal sinus
Authors: Badawy EA , Kanawati MN
Published: July 2009

Background  Pilonidal sinus (PNS) is chronic inflammatory process of the skin in the natal cleft. Management of PNS is mainly surgical. Although different types of surgery have been performed, the recurrence rate is still high.

Objective  To evaluate the effectiveness of laser hair removal (LHR) in the natal cleft area on the recurrence rate of PNS as an adjuvant therapy after surgical treatment.

Methods  Twenty five patients with PNS were included in this study. Fifteen patients underwent LHR treatment using Nd:YAG laser after surgical excision of PNS (Patients group) while ten subjects with PNS did not do LHR and served as a control group.

Results  All of the patients were male patients. Their age ranged from 17 to 29 years with a mean of 21.60 ± 3.13 years. They had Fitzpatrick skin type III, IV and V. The patients have got 3 to 8 sessions of LHR (mean 4.87 ± 1.64). Follow up period lasted between 12 to 23 months. None of the patients, who underwent LHR, has required further surgical treatment to date. Seven patients out of ten in the control group have developed recurrent PNS. Pain was the most frequent side effect and it was seen in 6 patients (40%).

Conclusion  LHR can prevent the recurrence of PNS. LHR should be advised as an essential adjuvant treatment after surgical excision of PNS. In non‐complicated recurrent PNS, LHR is strongly advocated to be started before and continued after doing surgical treatment.
Trapper profiles and strategies: insights into sustainability from hunter behaviour
Authors: Kümpel N. F. , Rowcliffe J. M. , Cowlishaw G. , Milner‐Gulland E. J.
Published: July 2009

Hunters are the critical link between demand and supply of bushmeat. An understanding of the incentives that drive hunter behaviour might thus help to predict the impacts of hunting and inform management of bushmeat hunting systems. However, hunter behaviour has been generally under‐represented in studies of exploitation, in particular trapper behaviour, despite the fact that trapping is the most common form of hunting in central Africa. We collected data on hunter profiles and measures of catch and effort over 15 months in the Monte Mitra area of continental Equatorial Guinea, through interviews, hunter follows and an offtake survey. Younger trappers, and those not born in the village, were found to expend the greatest trapping effort. Trappers operated under three distinct strategies, reflecting different levels of effort and impact: low‐impact village trappers, medium‐impact forest trappers and high‐impact forest trappers. Among different measures of effort, time expended and distance travelled were found to be less important in predicting trapping success than the number of effective traps, a measure that incorporates trap age. Regular checking of traps was found to be important in reducing wastage and therefore increases trapping success. Trapping is currently the main hunting method in Monte Mitra, due to lower barriers to entry and higher profits compared with gun hunting, but increasing affordability and availability of guns and cartridges warns of a possible future switch to gun hunting in the area, which is likely to have adverse impacts on vulnerable species, particularly arboreal primates. An understanding of the influence of a hunter's profile on hunting effort and success enables a prediction of the impacts of socioeconomic changes on wildlife populations and management actions to improve hunting sustainability.
RELATIONSHIP BETWEEN THE COLORATION AND THE FIRING TECHNOLOGY USED TO PRODUCE SUSA GLAZED CERAMICS OF THE END OF THE NEOLITHIC PERIOD*
Authors: LAHLIL S. , BOUQUILLON A. , MORIN G. , GALOISY L. , LORRE C.
Published: July 2009

Ancient decorated potteries from Susa (Mesopotamia) dating from 4200 to 3700 bc, were studied in order to determine the origin and the nature of the raw materials used, and to identify the technological processes applied to make the ceramic bodies and their decorations. Bulk compositions were determined by particle induced X‐ray emission (PIXE), while the microstructure and the mineralogical phases were studied using scanning electron microscopy (SEM), energy dispersive X‐ray analyses (EDX) and X‐ray powder diffraction (XRD). The results showed that the raw materials used to elaborate these potteries were similar for all the ceramic bodies (carbonates and iron and magnesium‐rich clays containing sand), and for all the decorations (iron oxides, silica, potassic and alumina sources). The variations of coloration of the ceramics and of their decorations were due to different firing temperatures. The ranges of firing temperatures used by potters were evaluated on the basis of mineral stability domains.
Environmental enrichment alters dentate granule cell morphology in oldest‐old rat
Authors: Darmopil Sanja , Petanjek Zdravko , Mohammed Abdul H. , Bogdanović Nenad
Published: July 2009

The hippocampus of aged rats shows marked age‐related morphological changes that could cause memory deficits. Experimental evidence has established that environmental enrichment attenuates memory deficits in aged rats. We therefore studied whether environmental enrichment produces morphological changes on the dentate granule cells of aged rats. Fifteen male Sprague‐Dawley rats, 24 months of age, were randomly distributed in two groups that were housed under standard (n= 7) or enriched (n= 8) environmental conditions for 26 days. Quantitative data of dendritic morphology from dentate gyrus granule cells were obtained on Golgi–Cox stained sections. Environmental enrichment significantly increased the complexity and size of dendritic tree (total number of segments increased by 61% and length by 116%), and spine density (88% increase). There were large interindividual differences within the enriched group, indicating differential individual responses to environmental stimulation. Previous studies in young animals have shown changes produced by environmental enrichment in the morphology of dentate gyrus granule cells. The results of the present study show that environmental enrichment can also produce changes in dentate granule cell morphology in the senescent brain. In conclusion, the hippocampus retains its neuroplastic capacity during aging, and enriched environmental housing conditions can attenuate age‐related dendritic regression and synaptic loss, thus preserving memory functions.
Renal tubular expression of Toll‐like receptor 4 in cyclosporine nephrotoxicity
Authors: LIM BEOM JIN , HONG SOON WON , JEONG HYEON JOO
Published: July 2009

Lim BJ, Hong SW, Jeong HJ. Renal tubular expression of Toll‐like receptor 4 in cyclosporine nephrotoxicity. APMIS 2009; 117: 583–91.

Exploring the expression of Toll‐like receptor (TLR) in cyclosporine (CsA)‐induced renal injury in humans, we evaluated the expression of TLR4 in both biopsied renal tissue and cultured tubular cells. Immunohistochemical stains for TLR4, heat shock protein (HSP) 47, and HSP70 were performed in both pre‐ and post‐treatment biopsies obtained from 18 patients of minimal change nephrotic syndrome or IgA nephropathy treated with CsA, and the percentage of positive tubules was compared in each case. For in vitro experiments, HK‐2 cells were treated with CsA (2, 5, and 10 μg/ml) for 24, 48, and 72 h. TLR4 mRNA and protein were measured using real‐time RT‐PCR and Western blot. In addition, hypoxic effect was added by GasPak System. The tubular expressions of TLR4 (2.2 ± 1.2% vs 4.4 ± 2.0%, p < 0.001) and HSP70 (2.6 ± 2.8% vs 6.1 ± 4.2%, p = 0.002) were increased after CsA treatment. TLR4 mRNA and protein expression were also increased in a dose‐dependent manner. Hypoxia enormously increased TLR4 expression. In summary, CsA increased tubular expression of TLR4 and its ligand HSP70. As hypoxia was shown to be a strong stimulus for TLR4 expression, it can be said that TLR4 is influenced by both direct toxicity and impediment of renal microcirculation in human CsA nephrotoxicity.
FGFR3 is expressed and is important for survival in INA‐6, a human myeloma cell line without a t(4;14)
Authors: Våtsveen Thea K. , Brenne Anne‐Tove , Dai Hong Y. , Waage Anders , Sundan Anders , Børset Magne
Published: July 2009

Objectives:  Fibroblast growth factor receptor 3 (FGFR3) is a proto‐oncogene that is often dysregulated together with multiple myeloma SET‐domain (MMSET) by the immunoglobulin heavy chain (IGH) gene in t(4;14)pos multiple myeloma (MM) cells, and which is usually not expressed in MM cells without this translocation. Whether FGFR3 may play a role in MM cells without t(4;14) and the IGH‐MMSET fusion protein is unclear and is the focus of this report.

Methods:  FGFR3 expression was explored in cell lines with and without t(4;14) by fluorescence in situ hybridization (FISH), RT‐PCR and Western Blot. FGFR3 inhibitors SU5402 and PD173074 were used to explore the role of FGFR3 in these cells.

Results:  We discovered an amplification of the FGFR3 locus in INA‐6, a human MM cell line. We also demonstrated expression of FGFR3 mRNA and protein in the cells, probably caused by the extra copy of the gene. INA‐6 cells did not have t(4;14) and neither was there any involvement of the other IG loci in translocations with the FGFR3 gene. The FGFR3 inhibitors decreased the proliferation of INA‐6.

Conclusion:  The decreased viability and proliferation in INA‐6, following inhibition with FGFR3 inhibitors, indicates that FGFR3 may play a role also in cells without t(4;14) – and hence without high expression of MMSET, the ubiquitous oncoprotein in MM cells with t(4;14). This gives further credibility to the notion that FGFR3 expression is not just an epiphenomenon in t(4;14) MM, but an important part of the malignant phenotype.
Perceptions of Japanese and Canadian dental hygiene students towards their profession
Authors: Saito A , Tomita C , Sato Y , Cathcart G
Published: July 2009

Abstract:  Objectives:  The purpose of this study was to investigate perceptions towards the profession and level of self‐esteem of Japanese and Canadian dental hygiene students.

Methods:  Third year dental hygiene students enrolled in a Japanese and a Canadian dental hygiene programme were asked to participate in a survey study. An instrument was developed to obtain students’ opinions about the profession. The present study also explored dental hygiene students’ levels of self‐esteem, and the relationship with perceptions towards profession.

Results:  Scores for dimensions including ‘Motivation’, ‘Expectation’ and ‘Environment’ were significantly higher among the Canadian students over Japanese students. The level of explicit self‐esteem of the Canadian students was significantly higher than that of the Japanese students, and it was positively correlated with their expectations of the profession.

Conclusions:  There were significant differences in perceptions between Japanese and Canadian dental hygiene students. It is suggested that educational strategies should be planned to positively influence the students’ perceptions toward the profession and improve the level of self‐esteem.
Determining the important environmental variables controlling plant species community composition in mesotrophic grasslands in Great Britain
Authors: Kalusová Veronika , Le Duc Michael G. , Gilbert Joanne C. , Lawson Clare S. , Gowing David J.G. , Marrs Rob H.
Published: July 2009

Question: What is the relative importance of local site effects and selected important environmental variables in determining plant species composition? How do species respond to these environmental variables?

Location: Ten mesotrophic grassland sites of high conservation value in southern England.

Methods: Species cover was assessed in between 10 and 25 randomly selected 1‐m2 quadrats at each site. At each quadrat degree of waterlogging (W), soil Olsen extractable phosphorus (P) and soil pH were measured. Variation partitioning was used to separate site and soil effects, and HOF (Huisman, Olff & Fresco) modelling was used to produce response curves for the major species on soil gradients, based on coenoclines derived from partial canonical correspondence analysis (pCCA).

Results: Variation partitioning identified Site as the most important environmental variable (34.6%). Only 18.7% was accounted for by the three soil variables together; W (degree of waterlogging), P and pH accounted for 11.1%, 5.7% and 4.3%, respectively in raw form with 2.4% shared. However, when Site and the other soil variables were removed the variation explained reduced to 2.3% for W, 1.1% for P and 1.0% for pH. The species responses to each of these soil environmental factors could be separated into four types on each gradient. Most species were abundant at low W, low soil P and intermediate pH.

Conclusions: Site‐based factors were more important than the three soil variables, which were assumed to be directly or indirectly associated with productivity. This implies that each site has unique properties that are more important than the soil variables. The three soil factors were, however, significant and the groups of the most common species, based on significant response curves, can be used as a first approximation of indicators of environmental conditions in British mesotrophic grasslands for conservation. However, W accounted for most variation, and the current reliance on soil available P and soil pH for assessing conservation/restoration potential should be viewed with caution.
Does flooding of rice fields after cultivation contribute to wetland plant conservation in southern Brazil?
Authors: Rolon Ana S. , Maltchik Leonardo
Published: July 2009

Question: Does flooding of rice fields after cultivation contribute to wetland plant conservation in southern Brazil?

Location: Rice fields in the coastal plain of southern Brazil.

Methods: Six rice fields with different management practices were randomly selected (three dry rice fields and three flooded rice fields). Six collections were carried out over the rice cultivation cycle. Richness and biomass were measured using the quadrat method.

Results: A total of 88 macrophyte species was recorded. There was no statistical interaction between management practices and rice cultivation phases for macrophyte richness and biomass. Macrophyte species richness and biomass changed over time, but were similar between flooded and dry rice fields. The first three axes generated by detrended correspondence analysis explained 29% of the variation in species composition and the multivariate analysis of variance showed that there was a statistical interaction between management practices and agricultural periods.

Conclusions: Rice fields may help to conserve an important fraction of the aquatic macrophyte diversity of wetlands of southern Brazil by providing the setting up of a greater number of species within the agricultural landscape. However, rice fields must not be viewed as surrogate systems for natural wetlands. The difference in species composition between flooded and dry rice fields is interesting in terms of biodiversity conservation. If rice producers could keep part of their agricultural land flooded during the fallow phase, this management practice could be an important strategy for the conservation of biodiversity in areas where natural wetlands have been converted to rice fields.
Mercury Exposure Increases Circulating Net Matrix Metalloproteinase (MMP)‐2 and MMP‐9 Activities
Authors: Jacob‐Ferreira Anna L. B. , Passos Carlos J. S. , Jordão Alceu A. , Fillion Myriam , Mergler Donna , Lemire Mélanie , Gerlach Raquel F. , Barbosa Jr Fernando , Tanus‐Santos Jose E.
Published: July 2009

Abstract:  Mercury (Hg) exposure causes health problems that may result from increased oxidative stress and matrix metalloproteinase (MMP) levels. We investigated whether there is an association between the circulating levels of MMP‐2, MMP‐9, their endogenous inhibitors (the tissue inhibitors of metalloproteinases; TIMPs) and the circulating Hg levels in 159 subjects environmentally exposed to Hg. Blood and plasma Hg were determined by inductively coupled plasma‐mass spectrometry (ICP‐MS). MMP and TIMP concentrations were measured in plasma samples by gelatin zymography and ELISA respectively. Thiobarbituric acid‐reactive species (TBARS) were measured in plasma to assess oxidative stress. Selenium (Se) levels were determined by ICP‐MS because it is an antioxidant. The relations between bioindicators of Hg and the metalloproteinases levels were examined using multivariate regression models. While we found no relation between blood or plasma Hg and MMP‐9, plasma Hg levels were negatively associated with TIMP‐1 and TIMP‐2 levels, and thereby with increasing MMP‐9/TIMP‐1 and MMP‐2/TIMP‐2 ratios, thus indicating a positive association between plasma Hg and circulating net MMP‐9 and MMP‐2 activities. These findings provide a new insight into the possible biological mechanisms of Hg toxicity, particularly in cardiovascular diseases.
Angiogenic Factors in Endometriosis
Authors: TAYLOR ROBERT N. , LEBOVIC DAN I. , MUELLER MICHAEL D.
Published: July 2009

Abstract: Similar to tumor metastases, endometriotic implants require neovascularization to establish, grow, and invade. The peritoneal environment is ideally suited to provide a proangiogenic milieu. Nevertheless, endometriotic lesions are found only in a minority of reproductive‐age women (∼10%) with retrograde menstruation. In this paper, we review the major cytokines, growth factors, steroid hormones, and eicosanoids responsible for angiogenesis in endometriosis. We postulate that interference with angiogenic principles expressed in the peritoneum may constitute novel therapeutic opportunities for the prevention, amelioration, or treatment of pelvic endometriosis.
The Protective and Anti‐Protective Effects of Ethanol in a Myocardial Infarct Model
Authors: KRENZ MAIKE , COHEN MICHAEL V. , DOWNEY JAMES M.
Published: July 2009

Abstract: Recent data indicate that acute alcohol exposure can have a preconditioning‐like protective effect on the heart. We investigated the effect of ethanol exposure shortly before regional ischemia in an infarct model. Both in the open‐chest rabbit and in the isolated rabbit heart, exposure of the heart to ethanol significantly reduced infarct size, but only if the alcohol were washed out or sufficiently metabolized before the onset of ischemia. If ethanol were still present during ischemia, it could not only prevent its own protective effect, but also abolish protection induced by ischemic preconditioning or the mitochondrial KATP channel activator diazoxide. In the in vitro model, we tested for possible mediators of ethanol‐induced protection and made comparisons to the signaling cascade of ischemic preconditioning. Neither adenosine receptor blockade with 8‐(p‐sulfophenyl) theophylline, scavenging of free radicals with N‐2‐mercaptopropionyl glycine, nor closure of KATP channels with glibenclamide affected ethanol's protective effect. However, either a PKC inhibitor or a protein tyrosine kinase inhibitor could completely block ethanol‐induced infarct size reduction. Both the protective and anti‐protective effects of ethanol had a threshold of about 5 mM. Thus, ethanol‐induced protection is mediated by protein kinase C and at least one protein tyrosine kinase, but, in contrast to ischemic preconditioning, is not triggered by either adenosine receptors, free radicals, or KATP channels. Ethanol can only exert its protective effect if it is removed before the onset of ischemia. If still present during ischemia, ethanol has the opposite effect, and inhibits preconditioning by an as yet unidentified mechanism.
Absorption and Metabolism of Antioxidative Polyphenolic Compounds in Red Wine
Authors: YAMASHITA SHINJI , SAKANE TOSHIYASU , HARADA MASAMI , SUGIURA NAMINO , KODA HIROFUMI , KISO YOSHINOBU , SEZAKI HITOSHI
Published: July 2009

Abstract: We have shown that drinking red wine reduces oxidation of LDL. This reduction in oxidation has been attributed to the polyphenolic compounds in red wine, but the mechanisms of absorption and metabolism of these compounds has been unclear. We therefore investigated the absorption and metabolism of polyphenols using rats to identify their active forms in biological fluids. We also investigated the effect of tartaric acid (TA), a major organic acid in wine, on the absorption of polyphenols. Our results suggested that low molecular weight polyphenols are absorbed in the intestine and metabolized to their glucuronide conjugates, which exhibit antioxidative activity in plasma, and that TA can enhance the bioavailability of wine polyphenols.
Regulation of Caspases by Nitric Oxide
Authors: KIM PETER K.M. , KWON YOUNG‐GUEN , CHUNG HUN‐TAEG , KIM YOUNG‐MYEONG
Published: July 2009

Abstract:Nitric oxide can prevent or induce apoptosis depending on its concentration, cell type, and the oxidative milieu. Nitric oxide inhibits apoptosis and inflammation byS‐nitrosylation of the active site cysteine of caspases, the central effector molecules of cell death as well as maturation of IL‐1β and IL‐18. The ability of nitric oxide toS‐nitrosylate caspases depends on multiple factors including the presence of free iron and intracellular redox potential. There are no known direct effects of nitric oxide on promoting caspase activation or activity. However, nitric oxide has been shown to promote apoptotic pathways in numerous cell types through the indirect activation of caspases. In this article we review the relationship of nitric oxide and caspase activity, modulation of this effect by iron, and clinical implications for the use of nitric oxide in regulating inflammation and apoptosis.
Contradictory Effects of Sodium Nitroprusside andS‐Nitroso‐N‐Acetylpenicillamine on Oxidative Stress in Brain Dopamine Neuronsin Vivo
Authors: RAUHALA PEKKA , ANDOH TSUGUNOBU , YEH KEVIN , CHIUEH CHUANG C.
Published: July 2009

Abstract:To investigate whether nitric oxide (•NO) is neurotoxic or neuroprotective in the brain, we compared thein vivorole ofS‐nitroso‐N‐acetylpenicillamine (SNAP) with that of sodium nitroprusside (SNP) on ferrous citrate‐induced oxidative stress and neuronal loss in the rat nigrostriatal dopaminergic system. It is known that light irradiation releases •NO from its donor compounds; these irradiated •NO donors were used as sham controls in this study. Intranigral infusion of ferrous citrate (4.2 nmol) into the rat midbrain substantia nigra compacta area caused acute lipid peroxidation in the substantia nigra and chronic dopamine depletion in the caudate nucleus. Coinfusion of freshly prepared SNAP (0‐8.4 nmol) or •NO (about 2 nmol), but not SNP, rescued iron‐induced dopamine depletion in the rat brainin vivo. In fact, SNP produced prooxidative effects similar to ferrous citrate bothin vivoandin vitro, since SNP is a redox iron complex. Consistently, •NO and SNAP inhibited, whereas SNP potentiated, •OH generation and lipid peroxidation evoked by ferrous citratein vitro. We previously reported that freshly prepared, but not irradiated,S‐nitroso‐l‐glutathione (GSNO) protected brain dopamine neurons against oxidative stressin vivo. As well as these antioxidative properties, our recent reports (seeRef. 1) indicate that •NO/GSNO activated guanylyl cyclase, increased cGMP and that could lead to PKG‐mediated expression of MnSOD, Bcl‐2, and thioredoxin for preconditioning neuroprotection against 1‐methyl‐4‐phenylpyridinium (MPP+).1In conclusion, •NO andS‐nitrosothiols (e.g., GSNO and SNAP) can scavenge reactive oxygen species and activate the heme moiety of guanylyl cyclase, resulting in protection of brain dopamine neurons through both antioxidative and antiapoptotic mechanisms.
Nitric Oxide Protects Astrocytes from Oxidative Stress
Authors: ROBB SARA J. , CONNOR JAMES R.
Published: July 2009

Abstract: Oxidative stress in astrocytes has been observed in a number of pathological conditions, however the effect of nitric oxide on oxidatively stressed astrocytes remains unclear. The goal of this research was to determine how nitric oxide influences the mechanism of peroxide‐induced oxidative stress in astrocytes. We used enriched mouse‐astrocyte cultures and tertiary‐butyl hydroperoxide to study astrocyte oxidative stress. Cellular integrity was measured at the ultrastructural level by electron microscopy and plasma membrane integrity measured by lactate dehydrogenase release. Mitochondrial swelling and disruption of cristae were observed by electron microscopy in the absence of damage to other organelles. Astrocytes exposed to peroxide eventually succumbed to necrotic loss of plasma membrane integrity. However, when astrocytes were subjected to oxidative stress in the presence of nitric oxide, mitochondrial integrity was preserved and cell death delayed. This protection of nitric oxide resembled that of iron chelation and nitric oxide reduced susceptibility usually associated with iron‐loaded astrocytes exposed to oxidative stress. Taken together, these data suggest that nitric oxide can act as a powerful antioxidant for astrocytes preserving mitochondrial and cellular integrity during oxidative stress.
Regulation of Endothelial Nitric Oxide Synthase Activity and Gene Expression
Authors: WU KENNETH K.
Published: July 2009

Abstract:Endothelial nitric oxide synthase (eNOS) is constitutively expressed in endothelial cells lining the blood vessel and the heart. It plays a major role in vascular and tissue protection. Its activity is tightly controlled by an intramolecular autoinhibitory element that hinders calmodulin binding. This molecular hindrance is removed by elevated intracellular calcium levels. The catalytic activity of eNOS is augmented by phosphorylation of a C‐terminal serine residue (Ser‐1177 of human eNOS) through the phosphatidyl‐3 kinase (PI‐3K)/Akt pathway. Its activity is also enhanced by binding to heat shock protein‐90. These two processes are calcium independent. The two biochemical events appear to facilitate calmodulin access to its binding site. eNOS is upregulated at the transcriptional level. Its upregulation is mediated by an increased Sp1 binding to its cognate site on eNOS promoter/enhancer region via the action of protein phosphatase 2A (PP2A). PP2A is activated by a signaling pathway including PI‐3γ→ Janus activated kinase 2 (Jak2) → MEK‐1 → ERK1 and 2. The transcriptional and posttranslational enhancement of eNOS activity is two‐ to threefold above the basal level. A higher magnitude of augmentation of eNOS gene expression can be achieved by gene transfer, which confers protection against vascular diseases and ischemia‐induced tissue injury in experimental animals. These findings provide new insight into the protective role of eNOS and the therapeutic potential of eNOS gene therapy.
Ginseng, Sex Behavior, and Nitric Oxide
Authors: MURPHY LAURA L. , LEE TONY JER‐FU
Published: July 2009

Abstract:In Asia, ginseng is commonly included in herbals used for the treatment of sexual dysfunction. Recent studies in laboratory animals have shown that both Asian and American forms of ginseng enhance libido and copulatory performance. These effects of ginseng may not be due to changes in hormone secretion, but to direct effects of ginseng, or its ginsenoside components, on the central nervous system and gonadal tissues. Indeed, there is good evidence that ginsenosides can facilitate penile erection by directly inducing the vasodilatation and relaxation of penile corpus cavernosum. Moreover, the effects of ginseng on the corpus cavernosum appear to be mediated by the release and/or modification of release of nitric oxide from endothelial cells and perivascular nerves. Treatment with American ginseng also affects the central nervous system and has been shown to significantly alter the activity of hypothalamic catecholamines involved in the facilitation of copulatory behavior and hormone secretion. Recent findings that ginseng treatment decreased prolactin secretion also suggested a direct nitric oxide‐mediated effect of ginseng at the level of the anterior pituitary. Thus, animal studies lend growing support for the use of ginseng in the treatment of sexual dysfunction and provide increasing evidence for a role of nitric oxide in the mechanism of ginsenoside action.
Mechanisms of Hepatoprotection by Nitric Oxide
Authors: WANG YINNA , VODOVOTZ YORAM , KIM PETER K.M. , ZAMORA RUBEN , BILLIAR TIMOTHY R.
Published: July 2009

Abstract:Nitric oxide (NO) exerts numerous antiapoptotic effects on hepatocytes in settings of inflammation and tissue damage. These actions of NO are modulated by a variety of mechanisms under both physiologic and pathologic conditions. Nitric oxide inhibits cell death or apoptosis by modulation of heat shock proteins,S‐nitrosylation of caspases at their catalytic site cysteine residue, triggering of the cGMP pathway, and prevention of mitochondrial dysfunction. Our preliminary studies also suggest that NO can modulate apoptosis‐related genes in a manner consistent with an antiapoptotic effect. This review focuses on these molecular mechanisms of cytoprotection by NO.
Neuroimmunoendocrinology of the Rheumatic Diseases
Authors: WILDER RONALD L.
Published: July 2009

Abstract:Adaptation to stressful stimuli, maintenance of homeostasis, and ultimately, survival require bidirectional feedback communication among components of the stress response and immune and endocrine systems. Substantial progress has been made in delineating molecular, cellular, and systemic physiologic mechanisms underlying this communication, particularly mechanisms that target the immune system. For example, our understanding of the immunomodulatory activities of numerous neuroendocrine mediators, such as cortisol, estrogen, testosterone, DHEA, catecholamines, corticotropin‐releasing hormone, and adenosine, has advanced substantially. Substantial progress has also been made in defining how abnormalities involving these factors may contribute to the initiation, progression, and severity of autoimmune rheumatic diseases, particularly rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). For RA, the available data support the view that inflammatory and immune system inhibitory mechanisms, involving the hypothalamic‐pituitary‐adrenal (HPA) axis and sympathetic nervous system are deficient. Age, gender, and reproductive status acting, in part, through gonadal hormonal effects on disease susceptibility genes also appear likely to modulate the inhibitory stress response systems and immune function. Animal model data also have provided direct evidence that many autoimmune disease regulatory genes are gender influenced. For SLE, a growing body of recent data indicates that estrogens and androgens exert contrasting effects on B‐lymphocytes (i.e., estrogens enhance and testosterone suppresses autoantibody production). These observations provide potential new insights into SLE pathogenesis and gender differences in prevalence. Continued investigation will refine our understanding of these observations and will uncover even more extensive interactions of the nervous, immune, and endocrine systems. Moreover, it is highly likely that improved understanding of these interactions will translate into improved therapy for the rheumatic diseases.
Regulation of Leukocyte‐Endothelial Interactions by Glucocorticoids
Authors: PITZALIS COSTANTINO , PIPITONE NICOLÒ , PERRETTI MAURO
Published: July 2009

Abstract: Glucocorticoids (GCs) are steroid molecules endowed with powerful anti‐inflammatory and immunosuppressive properties. Traditionally, the anti‐inflammatory action of GC has been largely ascribed to the synthesis of lipocortin‐1 (now know as annexin I), while the immunosuppressive effect has been linked to the inhibition of several immune functions and the synthesis of important cytokines and chemokines. In addition to these modes of action, there is a mounting body of evidence suggesting that GCs can also inhibit cell adhesion events, which also play a crucial role in the inflammatory/ immune response. The mechanisms by which GCs modulate cell adhesion are complex and multifactorial. It is now clear that GCs can directly regulate cell adhesion molecule (CAM) gene transactivation through the classical glucocorticoid receptor (GR) pathways. These involve interference with activation/ transcription factors such as AP‐1 and NF‐κB, as well as binding of the GC‐GR complex to specific DNA sequences, called glucocorticoid response element “GRE,” with ensuing CAM gene inhibition. In addition to these “genomic” mechanisms, there is increasing recognition of alternative modalities of action of GC that are independent from modulating gene expression and for this reason defined as “non‐genomic.” These are characterized by a rapid response (seconds/minutes) and insensitivity to inhibitors of gene transcription and protein synthesis. The non‐genomic effects could be due to direct physicochemical interactions with cell membrane constituents including ion channels and membrane associated proteins. This would lead to inhibition of intracellular signaling pathways involved in CAM activation and cytoskeleton reorganization essential for cell adhesion and locomotion.
A Role for Sex Steroids in Autoimmune Diseases
Authors: CASTAGNETTA LUIGI , GRANATA ORAZIA M. , TRAINA ADELE , COCCIADIFERRO LETIZIA , SAETTA ANNALISA , STEFANO ROSALBA , CUTOLO MAURIZIO , CARRUBA GIUSEPPE
Published: July 2009

Abstract: In recent years there has been a continuingly increasing interest in novel research subjects, as yet poorly explored, either because they relate to aspects previously thought to be marginal with respect to classical fields of investigation, or because they require both specialized competence and intense cross‐talk by researchers from disparate areas. The potential interaction between immunity and cancer has generated a remarkable number of studies, including those related to the newly explored immune‐neuro‐endocrine system. In this paper, we review a few autoimmune diseases as examples of a mutual relationship between immune diseases and malignancies. We also review our previous studies on patients with rheumatoid arthritis (RA). In particular, aiming to define the hormone‐responsive or ‐sensitive status of synovial tissues and cells, we have inspected different endocrine end‐points, including (1) high‐ and low‐affinity sites of androgen and estrogen binding; (2) the activity of key enzymes of steroid metabolism; and (3) the hormonal profile of synovial fluids as an indication of local endocrine milieu. Overall, our data provide convincing evidence for synovial macrophage‐like cells and a subset of T lymphocytes to be considered as target cells for gonadal steroids. This provides a basis for developing new strategies for alternative treatments of RA and possibly unveils novel perspectives in both research and the clinic for other autoimmune diseases as well. In addition, the association of autoimmunity and cancer may disclose promising new avenues of research linking steroid hormones, the immune system, and malignant transformation.
Effects of Stress on Serum Prolactin Levels in Patients with Systemic Lupus Erythematosus
Authors: DOSTÁL C. , MAREK J. , MOSZKORZOVÁ L. , LACINOVÁ Z. , MUSILOVÁ L. , ZVÁROVÁ J.
Published: July 2009

Abstract: The results of a study of effects of stress on serum prolactin (PRL) levels in patients with SLE reveal statistically significant differences in serum PRL level readings in samples taken over a short period of time, thus corroborating the need to take into account PRL stress induction during sample withdrawals and to interpret the values obtained, especially where moderate idiopathic hyperprolactinemia was detected. To eliminate any external stress factors, it is advisable to take PRL samples repeatedly and in perfectly resting patients.
Somatotropic, Lactotropic and Adrenocortical Responses to Insulin‐Induced Hypoglycemia in Patients with Rheumatoid Arthritis
Authors: ROVENSKY JOZEF , BAKOŠOVÁ JANA , KOŠKA JURAJ , KŠINANTOVÁ LUCIA , JEŽOVÁ DANIELA , VIGAŠ MILAN
Published: July 2009

Abstract: Neuroendocrine mechanisms have been suggested to play an important role in the onset and progression of rheumatoid arthritis (RA). The aim of this study was to evaluate hypothalamic‐pituitary functions in RA patients by measurement of hormone responses to insulin‐induced hypoglycemia. Insulin‐hypoglycemia (Actrapid HM 0.1 IU/kg, i.v. as a bolus) was induced in 17 male patients and in 11 age‐, gender‐, and weight‐matched healthy subjects. Concentrations of growth hormone (GH), prolactin (PRL) and cortisol were analyzed in plasma. PRL release after thyreoliberin stimulation (TRH, 200 g, i.v.) was determined in 21 patients with active forms of RA and in 12 control subjects to evaluate pituitary lactotropic response. In RA patients, basal concentrations of glucose, GH, PRL, and cortisol were in the normal range and they were comparable to those in the control group. Stress of hypoglycemia induced significant elevation of GH, PRL, and cortisol concentrations in all groups. Cortisol responses to hypoglycemia were comparable in patients and in control subjects. GH release during hypoglycemia was increased (p < 0.05) and PRL response was attenuated (p < 0.05) in RA patients versus control subjects. After TRH administration, PRL response was the same in patients as in healthy subjects. In conclusion, the present study revealed an altered hypothalamic‐pituitary function in patients with RA, namely, an enhanced somatotropic and reduced lactotropic activation in response to insulin‐induced hypoglycemia. Basal hormone levels and cortisol release during hypoglycemia were similar to those in healthy subjects.
Involvement of the Hypothalamic‐Pituitary‐Adrenal Axis in Children with Oligoarticular‐Onset Idiopathic Arthritis
Authors: PICCO P. , GATTORNO M. , SORMANI M. P. , VIGNOLA S. , BUONCOMPAGNI A. , BATTILANA N. , PISTOIA V. , RAVAZZOLO R.
Published: July 2009

Abstract: Adult patients with rheumatic arthritis and other rheumatic disorders show inappropriate cortisol secretion and peculiar CRH promoter gene polymorphisms. So far, no data are available about this topic in children with juvenile idiopathic arthritis (JIA). We have studied a series of 13 prepubertal patients (10 female, 3 male) affected with oligoarticular JIA (o‐JIA) without clinical and biological signs of disease activity (ESR and IL‐6). ACTH plasma concentrations were significantly increased at 8 a.m. in o‐JIA patients, whereas no differences were found in cortisol plasma concentrations. The ACTH/cortisol ratio was significantly increased in o‐JIA patients with respect to the normal population both at 8 a.m. and at noon. DHEAS and testosterone plasma concentration did not statistically differ in the two populations. The genetic study was aimed at defining the prevalence of polymorphisms A1 and A2 in o‐JIA patients, but we failed to find allelic or genotypic differences. Our study suggests the presence of a partial resistance to ACTH with a dysregulated pattern of secretion also in inactive o‐JIA patients. These preliminary data need further confirmation in larger pediatric studies.
Cytokines, Acute‐Phase Proteins, and Hormones
Authors: BURGER DANIELLE , DAYER JEAN‐MICHEL
Published: July 2009

Abstract: The cytokine network is a homeostatic system that has to be perceived in an analogous fashion to the acid/base equilibrium. The level of any cytokine in biological fluids can be interpreted correctly only by taking into account the levels of other synergistic cytokines, of their respective inhibitors, and of each cytokine receptor. Due to their potent activities in many different processes (including cell growth and differentiation, development, and repair processes leading to the restoration of homeostasis), the cytokine activities have to be tightly controlled by natural inhibitory mechanisms. Since one of the main functions of cytokines is to mediate interactions between the immune and inflammatory system, it is thought that chronic immuno‐inflammatory diseases might be caused in part by the uncontrolled production of cytokines. Depending on the stage of inflammation or the biological effect determined, the same cytokine might be pro‐ or anti‐inflammatory. This applies, for instance, to IL‐4, IL‐10, and TGFβ. An important mechanism that triggers the production of pro‐inflammatory cytokines in chronic inflammatory diseases is the direct cellular contact between stimulated T cells and monocyte‐macrophages. This mechanism is blocked at the systemic level by the “negative” acute‐phase protein apolipoprotein A‐I (apo A‐I). The levels of expression of cytokines and cytokine inhibitors and acute‐phase proteins are ruled by hormones. Estrogens as well as androgens inhibit the production of IL‐1β and TNF‐α on monocyte‐macrophages. However, androgens antagonize estrogen stimulatory effects on apo A‐I synthesis by the liver. Other studies suggest that estradiol is more inhibitory to Thl cytokines (e.g., IFNγ, IL‐2), while testosterone is inhibitory to Th2 cytokines (e.g., IL‐4). Cytokines also control the axis of the hypothalamic‐hypophyseal‐adrenal glands as well as the sexual hormones. The discrepancy between studies would suggest that the mechanisms are different in physiological and pathophysiological conditions.
Involvement of the Glucocorticoid Receptor in the Pathogenesis of Rheumatoid Arthritis
Authors: NEECK GUNTHER , KLÜTER ANDREAS , DOTZLAW HELMUT , EGGERT MARTIN
Published: July 2009

Abstract: The glucocorticoid receptor (GR) is a ligand‐inducible transcription factor which controls the expression of several genes. Its cognate ligand, the glucocorticoids, induces receptor activation by binding to the cytoplasmic located receptor, ultimately leading to translocation of the receptor/hormone complex into the nucleus and the regulation of gene activity. Because glucocorticoids are widely used for suppression of inflammation in rheumatoid arthritis (RA), we investigated whether the expression level of GR is correlated with RA. We designed a study to detect the total amount of GR in lymphocytes of untreated RA patients, glucocorticoid‐treated RA patients, and healthy controls. We observed a significant change in the expression levels of GR. Untreated RA patients exhibited a significantly higher amount of GR than the healthy controls, whereas glucocorticoid‐treated RA patients showed a strongly decreased receptor density. These results seem to reflect a functional dysregulation of the HPA axis and may lead to a better understanding of the pathogenesis of RA.
Regulatory Subunits of PKA and Breast Cancer
Authors: MILLER W. R.
Published: July 2009

Abstract:Overexpression of the R subunits of PKA (in particular, RI) is associated with high proliferation in normal breast, malignant transformation in the breast, poor prognosis in established breast cancer, and resistance to antiestrogens. These data, together with the observation that successful antiestrogen therapy is associated with reduced expression of RI mRNA, suggest that targeting R subunits is an appropriate therapeutic strategy for breast cancer. Initial experimental results, using antisense RI oligonucleotides, are promising in terms of reducing the growth rate of breast cancer cells and xenografts. While clinical trials designed to target RI subunits have yet to be established (and interventions as preventative measures are even more distant), the concept of these approaches to prevent and treat breast cancer should be developed and exploited.
Signaling Pathways in Adrenocortical Cancer
Authors: KIRSCHNER LAWRENCE S.
Published: July 2009

Abstract:Adrenocortical carcinoma is a rare tumor that carries a very poor prognosis. Despite efforts to develop new therapeutic regimens to treat this disease, surgery remains the mainstay of treatment. Laboratory studies of adrenocortical cancers have revealed a wide variety of signaling pathways that can be altered in these neoplasms. Although ACTH signaling through adenylyl cyclase and protein kinase A is important for normal adrenal cellular physiology, there is evidence to suggest that this pathway may inhibit the growth of adrenocortical tumors, and that inactivation of the ACTH receptor may promote tumor formation. Although multiple signal transduction pathways are essential for normal adrenal growth and hormone secretion, efforts to identify events required for neoplastic transformation have met with limited success. Alterations that have frequently been observed in adrenocortical carcinoma include up‐regulation of the IGF‐II system, as well as mutations inTP53andRAS. Current studies aim to elucidate the mechanisms of tumor growth by studying proproliferative signaling pathways, such as those involving Akt/PKB and the mitogen‐activated protein kinases (MAPKs). Although studies of single pathways have been helpful in guiding investigations, new tools to study the integration and multiplicity of signaling pathways hold the hope of improved understanding of the signaling pathway alterations in adrenocortical cancer.