EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 12 2002
Pierre-O.
Abstract Evidence suggests that dopamine is involved in the modulation of striatal excitotoxic processes. To further investigate this issue, we studied the effects of systemic ,low-dose' (total dose, 340 mg/kg in 7 days) 3-nitropropionic acid (3-NP) intoxication in dopamine transporter knock-out mice (DAT,/,) compared to wildtype (DAT+/+) mice. Systemic ,low-dose' 3-NP induced a significant impairment in a rotarod task only in DAT,/, mice. Histopathology also demonstrated a significant reduction of the striatal volume (,7%, P < 0.05), neuronal density (,12.5%, P < 0.001) and absolute number estimates of striatal neurons (,11.5%, P < 0.001) in DAT,/, compared to DAT+/+ mice, with increased glial activation, independent of the degree of succinate dehydrogenase inhibition. These findings strengthen the hypothesis for dopamine modulation of excitotoxicity within the nigrostriatal system. [source]

Fungal endophytes reduce regrowth and affect competitiveness of meadow fescue in early succession of pastures

GRASS & FORAGE SCIENCE, Issue 3 2010
S. Saari
Abstract Systemic- and seed-transmitted fungal endophytes are suggested to enhance competitive dominance of agronomic grasses by increasing plant growth and defence against herbivores. We studied whether Neotyphodium uncinatum endophyte infection frequencies of meadow fescue (Schedonorus pratensis) and botanical composition of pastures are affected by 4, 5, 7 and 21 years of grazing by dairy cattle. We then examined with one greenhouse and two field experiments, whether endophyte infection and clipping affect regrowth of young or mature plants relative to nutrient availability in soil. The frequencies of infected plants and the number of plant species were less in grazed parts of the pastures. Endophytes significantly reduced relative regrowth and dry biomass of regrowth of the grass irrespective of nutrient levels in a 1-year-old field (on an average 18% in 2 months) and under high nutrient conditions in the greenhouse experiment (on an average 3% in 3 months) respectively. However, effects of endophytes were not detected in 5-year-old fields and under low nutrient conditions in the greenhouse. In contrast to past studies, our results demonstrate that grazing may negatively affect endophyte,grass symbiosis and number of plant species of successional pastures, and suggest that the effects of endophytes may be linked to the ontogeny of the host. [source]

Systemic, renal, and hepatic hemodynamic derangement in cirrhotic patients with spontaneous bacterial peritonitis

HEPATOLOGY, Issue 5 2003
Luis Ruiz-del-Arbol M.D.
Spontaneous bacterial peritonitis (SBP) is frequently associated with renal failure. This study assessed if systemic and hepatic hemodynamics are also affected by this condition. Standard laboratory tests, tumor necrosis factor , (TNF-,) in plasma and ascitic fluid, plasma renin activity (PRA) and norepinephrine (NE), and systemic and hepatic hemodynamics were determined in 23 patients with SBP at diagnosis and after resolution of infection. Eight patients developed renal failure during treatment. At diagnosis of infection, patients developing renal failure showed significantly higher values of TNF-,, blood urea nitrogen (BUN), PRA and NE, peripheral vascular resistance, and hepatic venous pressure gradient (HVPG) and lower cardiac output than patients not developing renal failure. During treatment, a significant reduction in cardiac output and arterial pressure and increase in PRA and NE, HVPG, and Child-Pugh score were observed in the first group but not in the second. Peripheral vascular resistance remained unmodified in both groups. Changes in PRA and NE correlated inversely with changes in arterial pressure and directly with changes in BUN, Child-Pugh score, and HVPG. Five patients in the renal failure group developed encephalopathy, and 6 died. In the group without renal failure, none of the patients developed encephalopathy or expired. In conclusion, patients with SBP frequently develop a rapidly progressive impairment in systemic hemodynamics, leading to severe renal and hepatic failure, aggravation of portal hypertension, encephalopathy, and death. This occurs despite rapid resolution of infection and is associated with an extremely poor prognosis. [source]

Smart Drug-Loaded Polymer Gold Nanoshells for Systemic and Localized Therapy of Human Epithelial Cancer

ADVANCED MATERIALS, Issue 43 2009
Jaemoon Yang
Near-infrared-light-sensitive multifunctional smart drug-loaded polymer gold nanoshells are fabricated as advanced prototypes, composed of chemotherapeutic agents (therapeutic antibody and anticancer drug-loaded polymeric nanoparticles) for systemic chemotherapy of human epithelial cancer and a polymer-based gold nanoshell for localized photothermal treatment by NIR light. [source]

Systemic and local cytokine production in quiescent ulcerative colitis and its relationship to future relapse: A prospective pilot study

INFLAMMATORY BOWEL DISEASES, Issue 6 2005
Takayuki Yamamoto MD
Abstract Background: The main aim of this prospective study was to examine whether systemic (plasma) and local (mucosal) cytokine production is a predictor of future relapse in patients with quiescent ulcerative colitis (UC). The impact of other clinical and laboratory parameters on relapse was also studied. Methods: Fifty consecutive patients with quiescent UC were included. At enrollment, blood and mucosal (rectal biopsies) samples were collected. All patients were followed up regularly for 1 year after enrollment. Plasma and mucosal cytokine levels were measured by enzyme-linked immunosorbent assay. To identify independent significant predictive factors for relapse, time-dependent analyses using the Kaplan-Meier method and the Cox proportional hazard model were performed. Results: Thirty-four patients remained in remission, and 16 patients relapsed during the 1-year follow-up. Higher interleukin (IL)-8 levels in the rectal mucosa were significantly associated with relapse. In contrast, IL-1,, IL-6, and tumor necrosis factor-, levels in the rectal mucosa were not associated with relapse. Conventional blood markers and plasma cytokines (IL-1,, IL-6, IL-8, and tumor necrosis factor-,) did not correlate with relapse. Among clinical factors, age and number of prior relapses were significantly associated with relapse. In multivariate analysis, a higher rectal mucosal IL-8 level (,160 pg/mg of tissue; hazard ratio, 4.7), younger age (<30 yr; hazard ratio, 7.3), and a greater number of prior relapses (,5; hazard ratio, 4.3) were independent significant risk factors for future relapse. Conclusions: Rectal mucosal IL-8 measurement might be an additional objective diagnostic tool that can predict relapse in patients with quiescent UC. [source]

Gingival health status in renal transplant recipients: relationship between systemic inflammation and atherosclerosis

INTERNATIONAL JOURNAL OF CLINICAL PRACTICE, Issue 4 2007
G. Genctoy
Summary Cardiovascular disease (CVD) is the leading cause of mortality in renal transplant recipients (RTR). Systemic and periodontal inflammation has been suggested to have a possible role in the development of atherosclerosis. In the present study, we aimed to investigate the relationship between gingival health status, inflammation and atherosclerosis in RTRs. Eighty-three RTR (50 male, 33 female) were enrolled in the study. Routine biochemical analyses, serum lipoproteins, C-reactive protein, fibrinogen, homocystein, parathyroid hormone (PTH) and cyclosporin A (CsA) trough levels were studied. All patients had 24-h ambulatory blood pressure monitoring and B-mode ultrasound of the common carotid arteries. Gingival status was evaluated by the Löe and Silness gingival index (GI). Mean GI value was 2.3 ± 0.5. Fifty patients (60.3%) had GI value , 2.1 (severe gingivitis; group A). Thirty-three patients (39.7%) had GI value < 2.1 (no or moderate gingivitis; group B). Age, carotid intima-media thickness (CIMT) and mean time on dialysis before transplantation were significantly higher in group A than in B. Systemic inflammation markers were not different between group A and group B. Mean CIMT was positively correlated with GI (r = 0.425; p = 0.001) and negatively correlated with high-density lipoprotein cholesterol (r = ,0.256; p = 0.023). After the correction for confounding variables, mean CIMT was still significantly correlated with GI (r = 0.376, p = 0.02). In RTR, gingival inflammation seems to be associated with CIMT in the absence of systemic inflammation. Thus, gingivitis may, in part, play a role in the development of systemic atherosclerosis without causing any aggravation in systemic inflammatory response. [source]

Systemic and barrier contraceptives for the dermatologist: a review

INTERNATIONAL JOURNAL OF DERMATOLOGY, Issue 8 2009
C. Stanley Chan MD
First page of article [source]

Systemic and local effects of long-term exposure to alkaline drinking water in rats

INTERNATIONAL JOURNAL OF EXPERIMENTAL PATHOLOGY, Issue 4 2001
Marina E.T. Merne
Alkaline conditions in the oral cavity may be caused by a variety of stimuli, including tobacco products, antacids, alkaline drinking water or bicarbonate toothpaste. The effects of alkaline pH on oral mucosa have not been systematically studied. To assess the systemic (organ) and local (oral mucosal) effects of alkalinity, drinking water supplemented with Ca(OH)2 or NaOH, with pH 11.2 or 12 was administered to rats (n = 36) for 52 weeks. Tissues were subjected to histopathological examination; oral mucosal biopsy samples were also subjected to immunohistochemical (IHC) analyses for pankeratin, CK19, CK5, CK4, PCNA, ICAM-1, CD44, CD68, S-100, HSP 60, HSP70, and HSP90. At completion of the study, animals in the study groups had lower body weights (up to 29% less) than controls despite equal food and water intake, suggesting a systemic response to the alkaline treatment. The lowest body weight was found in rats exposed to water with the highest pH value and starting the experiment when young (6 weeks). No histological changes attributable to alkaline exposure occurred in the oral mucosa or other tissues studied. Alkaline exposure did not affect cell proliferation in the oral epithelium, as shown by the equal expression of PCNA in groups. The up-regulation of HSP70 protein expression in the oral mucosa of rats exposed to alkaline water, especially Ca(OH)2 treated rats, may indicate a protective response. Intercellular adhesion molecule-1 (ICAM-1) positivity was lost in 6/12 rats treated with Ca(OH)2 with pH 11.2, and loss of CD44 expression was seen in 3/6 rats in both study groups exposed to alkaline water with pH 12. The results suggest that the oral mucosa in rats is resistant to the effects of highly alkaline drinking water. However, high alkalinity may have some unknown systemic effects leading to growth retardation, the cause of which remains to be determined. [source]

Health Financing in Singapore: A Case for Systemic Reforms

INTERNATIONAL SOCIAL SECURITY REVIEW, Issue 1 2006
Mukul G. Asher
This paper assesses Singapore's healthcare financing arrangements in terms of their efficiency, fairness, and adequacy. Singapore represents an interesting case study because it is perhaps the only high-income, rapidly ageing country to rely on mandatory savings to finance healthcare, thus eschewing extensive risk-pooling arrangements, generally regarded as efficient and equitable. The paper argues that parametric reforms, i.e. relatively minor changes in the parameters of current schemes which preserve the existing philosophy and system design, will not be sufficient to meet healthcare financing objectives. Systemic reforms, which will bring Singapore into the mainstream of health financing arrangements found in the OECD countries, are urgently needed. Their design and timing should be based on good quality, timely and relevant data, and an environment conducive to vigorous debate. [source]

Ethics in operations research and sustainable development

INTERNATIONAL TRANSACTIONS IN OPERATIONAL RESEARCH, Issue 4 2010
Jean-Pierre Brans
Abstract During the last 100 years, major social, economic, environmental and technical problems have arisen that today jeopardise mankind's very existence. The authors argue that operations research (OR) should be more strongly involved by developing models to face today's crucial challenges. OR should change drastically because it is traditionally involved mainly with optimisation problems, which are often counterproductive in the sense of ethical behaviour: new basic approaches are required. This paper provides some avenues on how to develop instruments for addressing mankind's sustainability problems, and for complying with ethical principles. It is proposed to have a mix of techniques, mainly: systems thinking, multi-criteria decision-making and dynamic control. A global framework, called ASMC (Adaptive, Systemic, Multi-criteria, Control procedure), is proposed for developing these ideas. Some sustainable development applications are presented. [source]

Systemic and mucosal antibody response in tilapia, Oreochromis niloticus (L.), following immunization with Flavobacterium columnare

JOURNAL OF FISH DISEASES, Issue 10 2004
L D Grabowski
Abstract Specific antibody responses to Flavobacterium columnare (isolate ATCC 23463T) were characterized in plasma and mucus of tilapia following intraperitoneal (i.p.) injection or immersion immunization with formalin-killed sonicated or whole cell preparations. Fish (30 per treatment) received a primary immunization and were booster immunized 4 weeks later. An enzyme-linked immunosorbent assay was developed for detection and quantification of specific anti- F. columnare antibody, and it was found that formalin-killed sonicated cells in Freund's complete adjuvant (FCA) injected i.p. stimulated a significant systemic antibody response within 2 weeks (mean titre 11 200) which increased to 30 600 following secondary immunization. At 10 weeks post-immunization, the mean titre remained significantly elevated above the controls. Antibodies were also observed in cutaneous mucus of fish immunized i.p. with formalin-killed sonicated cells in FCA at 6 and 8 weeks post-immunization (mean titres 67 and 33, respectively). Although some individual fish responded, mean plasma and cutaneous mucus antibody titres were not significantly greater than controls in any of the other treatment groups. The results of this study demonstrate that tilapia can mount a significant humoral response in plasma and cutaneous mucus to F. columnare, but i.p. immunization with FCA is required to elicit this response. [source]

Systemic to portal shunting following vena cava obstruction: Computed tomography and venographic appearances

JOURNAL OF MEDICAL IMAGING AND RADIATION ONCOLOGY, Issue 3 2002
LG Teh
SUMMARY Obstruction of the inferior or superior vena cava normally leads to the formation of a well-described and consistent pattern of collateral venous pathways. We present the angiographic and CT features of the unusual development of systemic to portal venous shunting in two cases with central vein obstruction. [source]

Systemic and topical corticosteroid treatment of oral lichen planus: a comparative study with long-term follow-up

JOURNAL OF ORAL PATHOLOGY & MEDICINE, Issue 6 2003
M. Carbone
Abstract Background:, Topical corticosteroids are the mainstay treatment for oral lichen planus (OLP), but some authors suggest that systemic corticosteroid therapy is the only way to control acute presentation of OLP. Methods:, Forty-nine patients with histologically proven atrophic,erosive OLP were divided into two groups matched for age and sex. The test group (26 patients) was treated systemically with prednisone (50 mg/day), and afterwards with clobetasol ointment in an adhesive medium plus antimicotics, whereas the control group (23 patients) was only treated topically with clobetasol plus antimycotics. Results:, Complete remission of signs was obtained in 68.2% of the test group and 69.6% of the control group, respectively (P = 0.94). Similar results were obtained for symptoms. Follow-up showed no significant differences between the two groups. One-third of the patients of the test group versus none in the control group experienced systemic side-effects (P = 0.003). Conclusions:, The most suitable corticosteroid therapy in the management of OLP is the topical therapy, which is easier and more cost-effective than the systemic therapy followed by topical therapy. [source]

Role of systemic and local administration of selective inhibitors of cyclo-oxygenase 1 and 2 in an experimental model of periodontal disease in rats

JOURNAL OF PERIODONTAL RESEARCH, Issue 2 2009
C. M. Queiroz-Junior
Background and Objective:, Periodontal disease is an inflammatory condition of tooth-supporting tissues. Arachidonic acid metabolites have been implicated in development of periodontal disease, especially those derived from the cyclo-oxygenase (COX) pathway. This study investigated the role of inhibitors of cyclo-oxygenases (COX-1 and COX-2) in a model of periodontal disease in rats. Material and Methods:, A ligature was placed around the molar of rats. Losses of fiber attachment and of alveolar bone were measured morphometrically in histologically prepared sections. Infiltration of cells into gingival tissue surrounding the ligated tooth was also determined. Results:, Systemic and local administration of non-selective and selective COX-2 inhibitors, preventively, resulted in significant reduction of the losses of fiber attachment and alveolar bone, as well as decreased leukocyte numbers in gingival tissue. Preventive selective inhibition of COX-1 was as effective as COX-2 inhibition in reducing local fiber attachment loss and cell migration, but did not prevent alveolar bone loss. Conclusion:, Our results provide evidence for participation of COX-1 and COX-2 in early stages of periodontal disease in rats. Furthermore, local administration of COX inhibitors reduced the signs of periodontal disease to the same extent as systemic treatment. Therapeutic approaches incorporating locally delivered anti-inflammatory drugs could be of benefit for patients suffering from periodontal disease. [source]

Nitric Oxide-Mediated Intestinal Injury Is Required for Alcohol-Induced Gut Leakiness and Liver Damage

ALCOHOLISM, Issue 7 2009
Yueming Tang
Background:, Alcoholic liver disease (ALD) requires endotoxemia and is commonly associated with intestinal barrier leakiness. Using monolayers of intestinal epithelial cells as an in vitro barrier model, we showed that ethanol-induced intestinal barrier disruption is mediated by inducible nitric oxide synthase (iNOS) upregulation, nitric oxide (NO) overproduction, and oxidation/nitration of cytoskeletal proteins. We hypothesized that iNOS inhibitors [NG-nitro- l -arginine methyl ester (l -NAME), l -N6 -(1-iminoethyl)-lysine (l -NIL)] in vivo will inhibit the above cascade and liver injury in an animal model of alcoholic steatohepatitis (ASH). Methods:, Male Sprague,Dawley rats were gavaged daily with alcohol (6 g/kg/d) or dextrose for 10 weeks ± l -NAME, l -NIL, or vehicle. Systemic and intestinal NO levels were measured by nitrites and nitrates in urine and tissue samples, oxidative damage to the intestinal mucosa by protein carbonyl and nitrotyrosine, intestinal permeability by urinary sugar tests, and liver injury by histological inflammation scores, liver fat, and myeloperoxidase activity. Results:, Alcohol caused tissue oxidation, gut leakiness, endotoxemia, and ASH. l -NIL and l -NAME, but not the d -enantiomers, attenuated all steps in the alcohol-induced cascade including NO overproduction, oxidative tissue damage, gut leakiness, endotoxemia, hepatic inflammation, and liver injury. Conclusions:, The mechanism we reported for alcohol-induced intestinal barrier disruption in vitro , NO overproduction, oxidative tissue damage, leaky gut, endotoxemia, and liver injury , appears to be relevant in vivo in an animal model of alcohol-induced liver injury. That iNOS inhibitors attenuated all steps of this cascade suggests that prevention of this cascade in alcoholics will protect the liver against the injurious effects of chronic alcohol and that iNOS may be a useful target for prevention of ALD. [source]

Systemic 5-fluorouracil producing an inflammatory response in porokeratosis

JOURNAL OF THE EUROPEAN ACADEMY OF DERMATOLOGY & VENEREOLOGY, Issue 2 2003
WK Nahm
ABSTRACT Topical 5-fluorouracil has been used as an effective treatment for porokeratosis. Upon its treatment, an inflammatory effect occurs with the topical 5-fluorouracil. We report a case of a patient with disseminated superficial actinic porokeratosis displaying a comparable inflammatory process following therapy with systemic 5-fluorouracil used to manage a metastatic breast cancer. [source]

Systemic and splanchnic haemodynamic effects of sildenafil in an in vivo animal model of cirrhosis support for a risk in cirrhotic patients

LIVER INTERNATIONAL, Issue 1 2004
Isabelle Colle
Abstract: Objectives: Sildenafil is a selective inhibitor of the cGMP-specific phosphodiesterase type V (PDE-V) in the corpus cavernosum. PDE-V is also present in the mesenteric artery. Cirrhosis is complicated by a splanchnic vasodilation attributed to a local overproduction of nitric oxide (NO). As sildenafil potentiates the effects of NO, it may further decrease mesenteric vascular tone and increase portal venous blood flow. The aim is to evaluate the effects of sildenafil on the systemic and splanchnic haemodynamics in an experimental model of cirrhosis. Methods: Secondary biliary cirrhosis was induced in male Wistar rats by common bile duct ligation (CBDL, n=8); control rats were sham-operated (sham, n=7). The mean arterial pressure (MAP), portal venous pressure (PVP) and arterial mesenteric blood flow (MBF) were measured after intramesenteric (0.01,10 mg/kg) and after intravenous (i.v.) (0.01,10 mg/kg) administration of sildenafil. Results: Baseline PVP was significantly higher in CBDL than in sham rats, whereas baseline MAP tended to be lower and MBF tended to be higher in CBDL compared with sham rats. Both intramesenteric and i.v. injection of sildenafil significantly decreased MAP and increased MBF and PVP in a dose-dependent way. The decrease in MAP was significantly less important in CBDL than in sham rats. The increase in MBF was importantly lower in CBDL than in sham rats. PVP tended to increase more significantly in sham rats than in CBDL. Conclusion: Sildenafil increases MBF and PVP and induces systemic hypotension. The effects are less pronounced in cirrhosis, suggesting vascular hyporesponsiveness to sildenafil. Although the rise in PVP in cirrhotic animals is smaller than in controls, it may present a risk for haemorrhagic complications. Further studies are necessary before prescribing sildenafil to patients with cirrhosis. [source]

The angiotensin II receptor blocker candesartan improves survival and mesenteric perfusion in an acute porcine endotoxin model

ACTA ANAESTHESIOLOGICA SCANDINAVICA, Issue 2 2004
M. Laesser
Background:, Blockade of the angiotensin II type 1 (AT1) receptor has been demonstrated to ameliorate splanchnic hypoperfusion in acute experimental circulatory failure. This study focused on hemodynamic changes and survival in pigs treated with AT1 blockade prior to or during acute endotoxinemia. Methods:,Escherichia coli lipopolysaccharide endotoxin was infused in anesthetized and mechanically ventilated pigs. Systemic, renal, mesenteric and jejunal mucosal perfusion as well as systemic oxygen and acid-base balance were monitored. The selective AT1 receptor blocker candesartan was administered prior to as well as during endotoxinemia. Control animals received the saline vehicle. Results:, Pre-treatment with candesartan resulted in higher survival rate (83%, 10 out of 12 animals) compared with 50% (6 of 12) in control animals and 27% (3 of 11) in animals treated during endotoxinemia. Pre-treatment with candesartan resulted in higher cardiac output, mixed venous oxygen saturation, arterial standard base-excess, portal venous blood flow during endotoxin infusion compared with controls and animals treated during endotoxinemia. No adverse effects were found on neither systemic nor renal circulation. Conclusion:, The favorable results of AT1 receptor blockade prior to endotoxinemia are lost when blockade is established during endotoxinemia demonstrating the importance of the renin-angiotensin system and its dynamic involvement in acute endotoxinemic shock. [source]

Systemic and specific treatment for a global disease: allergen immunotherapy revisited

ALLERGY, Issue 7 2006
M. L. Kowalski
First page of article [source]

A combination therapy of whole lung lavage and GM-CSF inhalation in pulmonary alveolar proteinosis

PEDIATRIC PULMONOLOGY, Issue 8 2008
Hajime Yamamoto MD
Abstract Systemic and inhalation therapy of granulocyte-macrophage colony-stimulating factor (GM-CSF) is usually effective in controlling autoimmune pulmonary alveolar proteinosis (PAP), but some cases are refractory to GM-CSF therapy and subjected to whole lung lavage (WLL). A 9-year-old girl developed severe respiratory failure due to autoimmune PAP was treated with inhalational 250 µg of GM-CSF daily, however, it was ineffective. Unilateral WLL was performed three times and subsequent GM-CSF inhalation therapy yielded marked physiological and radiological improvement and was continued for 1 year. Pediatr Pulmonol. 2008; 43:828,830. © 2008 Wiley-Liss, Inc. [source]

Inflammatory protein profile during systemic high dose interleukin-2 administration

PROTEINS: STRUCTURE, FUNCTION AND BIOINFORMATICS, Issue 2 2006
Leonardo Rossi
Abstract Systemic interleukin-2 (IL-2) administration induces an assortment of downstream effects whose biological and therapeutic significance remains unexplored mostly because of the methodological inability to globally address their complexity. Protein array analysis of sera from patients with renal cell carcinoma obtained prior and during high-dose IL-2 therapy had previously revealed extensive alterations in expression of the soluble factors analyzed, whose discovery was limited by the number of capture antibodies selected for protein detection. Here, we expanded the analysis to SELDI-TOF-MS and quantitative protein analysis (nephelometry). All cytokines/chemokines detected by protein arrays were below the SELDI detection limit, while novel IL-2-specific changes in expression of acute-phase reactants and high-density lipoprotein metabolites could be identified. Serum amyloid protein,A (SAA) and C-reactive protein expression were consistently up-regulated after four doses of IL-2, while other proteins were down-regulated. These findings were confirmed by SELDI immunoaffinity capture and nephelometry. Immunoaffinity capture revealed different, otherwise undetectable, isoforms of SAA. A linear correlation between peak area by SELDI and protein concentration by nephelometry was observed. Overall distinct yet complementary information was obtained using different platforms, which may better illustrate complex phenomena such as the systemic response to biological response modifiers. [source]

REVIEW ARTICLE: Immunological Modes of Pregnancy Loss

AMERICAN JOURNAL OF REPRODUCTIVE IMMUNOLOGY, Issue 6 2010
Joanne Kwak-Kim
Citation Kwak-Kim J, Park JC, Ahn HK, Kim JW, Gilman-Sachs A. Immunological modes of pregnancy loss. Am J Reprod Immunol 2010 During the implantation period, a significant portion of embryos are lost and eventually less than half of clinically established pregnancies end as full-term pregnancies without obstetrical complications. A significant portion of these pregnancy losses is associated with immune etiologies, including autoimmune and cellular immune abnormalities. Although an autoimmune etiology such as anti-phospholipid antibodies (APAs) has been reported to induce placental infarct and thrombosis at maternal,fetal interface, APAs induce inflammatory immune responses as well. Inflammatory immune responses, such as increased proportions of NK cells and Th1/Th2 cell ratios in peripheral blood are related to recurrent pregnancy losses and multiple implantation failures. Systemic and local inflammatory immune responses seem to be induced by activation of Toll-like receptors with infectious agents, fetal cell debris, or gonadotropin-releasing hormone agonist, etc. Cellular activation of T and NK cells leads to pro-inflammatory cytokine storm and consequently, placental infarction and thrombosis. Potential application of anti-inflammatory therapeutic agents for the prevention of pregnancy losses should be explored further. [source]

Preemptive Therapy for Systemic and Pulmonary Human Cytomegalovirus Infection in Lung Transplant Recipients

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
G. Gerna
The incidence and treatment of both systemic and pulmonary human cytomegalovirus (HCMV) infection as well as HCMV-specific T-cell immune responses were investigated in 57 consecutive lung transplant recipients (LTR) by using as cutoffs for preemptive therapy: 300 000 DNA copies/mL whole blood for systemic infections and 100 000 DNA copies/mL bronchoalveolar lavage fluid for lung infections. Results showed that out of 29/57 LTR (50.9%) needing preemptive antiviral therapy, 15 (51.7%) reached the blood cutoff, 8 (27.6%) the pulmonary cutoff and 6 (20.7%) both the blood and the lung cutoff (3 simultaneously and 3 subsequently). Recovery of HCMV-specific T-cell immune responses was achieved much earlier for CD8+ than CD4+ T cells. However, protection from HCMV reactivation was conferred by the presence of both arms of the T-cell response. In two LTR reaching the pulmonary cutoff and not preemptively treated, a full HCMV-specific CD4+ and CD8+ T-cell response was associated with resolution of lung infection. Antirejection steroid therapy suppressed T-cell immune responses, thus facilitating HCMV reactivation. In conclusion, in LTR, monitoring HCMV infection in both blood and lungs, may improve preemptive therapy efficacy. In addition, monitoring the HCMV-specific T-cell immune response appears useful for predicting control of HCMV infection in the posttransplant period. [source]

Outcome and prognostic factor analysis of 217 consecutive isolated limb perfusions with tumor necrosis factor-, and melphalan for limb-threatening soft tissue sarcoma

CANCER, Issue 8 2006
Dirk J. Grunhagen M.D.
Abstract BACKGROUND Extensive and mutilating surgery is often required for locally advanced soft tissue sarcoma (STS) of the limb. As it has become apparent that amputation for STS does not improve survival rates, the interest in limb-preserving approaches has increased. Isolated limb perfusion (ILP) with tumor necrosis factor-, (TNF) and melphalan is successful in providing local tumor control and enables limb-preserving surgery in a majority of cases. A mature, large, single-institution experience with 217 consecutive ILPs for STS of the extremity is reported. METHODS At a prospectively maintained database at a tertiary referral center, 217 ILPs were performed from July 1991 to July 2003 in 197 patients with locally advanced STS of the extremity. ILPs were performed at mild hyperthermic conditions with 1,4 mg of TNF and 10,13 mg/L limb-volume melphalan (M) for leg and arm perfusions, respectively. RESULTS The overall response rate was 75%. Limb salvage was achieved in 87% of the perfused limbs. Median survival post-ILP was 57 months and prognostic factors for survival were Trojani grade of the tumor and ILP for single versus multiple STS. The procedure could be performed safely, with a perioperative mortality of 0.5% in all patients with no age limit (median age, 54 yrs; range, 12,91). Systemic and locoregional toxicity were modest and easily manageable. CONCLUSION TNF+M-based ILP can provide limb salvage in a significant percentage of patients with locally advanced STS and has therefore gained a permanent place in the multimodality treatment of STS. Cancer 2006. © 2006 American Cancer Society. [source]

Effect of voriconazole on a corneal abscess caused by fusarium

ACTA OPHTHALMOLOGICA, Issue 6 2004
Anna Polizzi
Abstract. Purpose:, To describe a case of corneal abscess caused by Fusarium solani that did not respond to common antifungal agents. Method:, Case report. Results:, Twenty days after accidental contact with vegetation, a 56-year-old man presented with a corneal abscess. Corneal ulceration developed and a perforating keratoplasty was performed. After a microbiological examination, the diagnosis of F. solani infection was made. Systemic and topical amphotericin B and fluconazole were prescribed, with no results. A new abscess formed on the transplanted graft and a wound leak developed. We administered topical and systemic voriconazole. No side-effects were observed. The choroidal detachment and the surgical transplant recovered completely in 20 days. A vascular leukoma developed at the site of the transplanted corneal abscess. Conclusion:, From a functional point of view, another corneal transplant will be necessary. Voriconazole was effective in treating a severe keratomycosis caused by F. solani that was resistant to other topical and systemic antifungal agents. [source]

Imbalance between interleukin-1 agonists and antagonists: relationship to severity of inflammatory bowel disease

CLINICAL & EXPERIMENTAL IMMUNOLOGY, Issue 2 2004
O. LUDWICZEK
SUMMARY Interleukin (IL)-1 is a key mediator in the pathogenesis of inflammatory bowel disease (IBD). Naturally occurring IL-1 modulators include IL-1 receptor antagonist (IL-1Ra), IL-1 soluble receptor Type I (IL-1sRI), IL-1sRII and IL-1 receptor accessory protein (AcP). Systemic and mucosal levels of IL-1 soluble receptors remain unknown in IBD. Plasma or colonic tissues were obtained from 185 consecutive unselected patients with Crohn's disease (CD) or ulcerative colitis (UC) and from 52 control subjects. Plasma and colonic explant culture supernatants were assessed for IL-1,, IL-1,, IL-1Ra, IL-1sRI and IL-1sRII. Plasma IL-1Ra levels were higher in UC (+93%) than in healthy subjects. IL-1, and IL-1, were not detected. IL-1sRII levels were marginally lower in CD (,10%) and UC (,9%), whereas IL-1sRI levels were elevated in CD (+28%) only. Plasma IL-1sRI levels correlated positively (P < 0·01) with Crohn's disease activity index (r = 0·53), C-reactive protein (r = 0·46) and ,1-acid glycoprotein (r = 0·42). In colonic explant cultures, IL-1, and IL-1Ra levels were elevated in non-lesional (+233% and +185% respectively) and lesional CD (+353% and +1069%), lesional UC (+604% and +1138%), but not in non-lesional UC. IL-1, was elevated in lesional UC (+152%) and CD (+128%). In contrast, IL-1sRII levels were elevated in non-lesional CD (+65%), but remained unchanged in lesional CD, non-lesional and lesional UC. IL-1sRI levels did not differ between patient and control groups. These results indicate that (i) the proinflammatory moiety IL-1sRI is a systemic marker of inflammation and activity in CD and (ii) local shedding of the functional antagonist IL-1sRII may dampen colonic inflammation in CD, but not in UC. [source]

Imaging of the lymphatic system: new horizons,

CONTRAST MEDIA & MOLECULAR IMAGING, Issue 6 2006
Tristan Barrett
Abstract The lymphatic system is a complex network of lymph vessels, lymphatic organs and lymph nodes. Traditionally, imaging of the lymphatic system has been based on conventional imaging methods like computed tomography (CT) and magnetic resonance imaging (MRI), whereby enlargement of lymph nodes is considered the primary diagnostic criterion for disease. This is particularly true in oncology, where nodal enlargement can be indicative of nodal metastases or lymphoma. CT and MRI on their own are, however, anatomical imaging methods. Newer imaging methods such as positron emission tomography (PET), dynamic contrast-enhanced MRI (DCE-MRI) and color Doppler ultrasound (CDUS) provide a functional assessment of node status. None of these techniques is capable of detecting flow within the lymphatics and, thus, several intra-lymphatic imaging methods have been developed. Direct lymphangiography is an all-but-extinct method of visualizing the lymphatic drainage from an extremity using oil-based iodine contrast agents. More recently, interstitially injected intra-lymphatic imaging, such as lymphoscintigraphy, has been used for lymphedema assessment and sentinel node detection. Nevertheless, radionuclide-based imaging has the disadvantage of poor resolution. This has lead to the development of novel systemic and interstitial imaging techniques which are minimally invasive and have the potential to provide both structural and functional information; this is a particular advantage for cancer imaging, where anatomical depiction alone often provides insufficient information. At present the respective role each modality plays remains to be determined. Indeed, multi-modal imaging may be more appropriate for certain lymphatic disorders. The field of lymphatic imaging is ever evolving, and technological advances, combined with the development of new contrast agents, continue to improve diagnostic accuracy. Published in 2006 by John Wiley & Sons, Ltd. [source]

The Climate for Transformation: Lessons for Leaders

CREATIVITY AND INNOVATION MANAGEMENT, Issue 1 2007
Scott G. Isaksen
This article reports insights for organizational leaders based on a series of case studies describing the use of the Situational Outlook Questionnaire as a tool to assist them with their transformation efforts. Leaders often assert the need to change their organizational cultures. This article seeks to clarify and differentiate culture from climate, and then focus on what leaders can do to transform their climate by applying a deliberate assessment tool. As the case studies illustrate, making organizational transformation happen is best approached through a systemic or ecological approach. This approach includes considering the people involved, the methods deployed, the desired outcome of the change as well as the context within which the transformation occurs. The broadest concept within this framework is context, which includes both culture and climate, among other things. Since context is key to initiating and sustaining transformation, emphasis on the leader's role in climate creation will be provided. [source]

Approach to the patient with vulvovaginal complaints

DERMATOLOGIC THERAPY, Issue 5 2010
Bethanee J. Schlosser
ABSTRACT Although vulvovaginal diseases may seem daunting, dermatologists possess all of the requisite tools and skills necessary to comprehensively assess and accurately diagnose primary cutaneous, systemic, and inflammatory diseases that affect the vulva. A simple but comprehensive dermatologic approach to the patient with a vulvovaginal complaint is presented. We begin with a review of the normal vulvar anatomy and normal variants and proceed to the clinical approach with special emphasis on the history, physical examination, and common diagnostic procedures. [source]

Treatment of cutaneous T-cell lymphoma with retinoids

DERMATOLOGIC THERAPY, Issue 5 2006
Chunlei Zhang
ABSTRACT:, Retinoids are biologic regulators of differentiation, proliferation, apoptosis, and immune response. Retinoids (all- trans retinoic acid, 13- cis -retinoic acid, and the synthetic analogs isotretinoin, etretinate, and acitretin) have been used for years as monotherapy and/or in combination for treatment of cutaneous T-cell lymphomas (CTCL). Orally administered bexarotene, the first synthetic highly selective retinoid X receptor retinoid to be approved by the Food and Drug Administration for CTCL, was shown to be active against the cutaneous manifestations of all stages of CTCL. The topical gel formulation was also effective for early cutaneous manifestations of CTCL or as an adjunct to systemic or phototherapy. Use of retinoids in future long-term clinical trials and their eventual application in CTCL regiments will require strategies to decrease the side effects of existing retinoids, identify novel receptor subtype-selective retinoids with better therapeutic index, and explore biologically based synergistic combination therapies with other active agents. [source]