bluuebunny/crossref_metadata_2025_split huggingface dataset:
Involvement of interleukin‐1β, nerve growth factor and prostaglandin E2 in endotoxin‐induced localized inflammatory hyperalgesia
Authors: Safieh‐Garabedian Bared , Kanaan Salim A. , Haddad John J. , Abou Jaoude Pamela , Jabbur Suhayl J. , Saadé Nayef E. 
Published: August 2006

Intraplantar endotoxin (ET) injection (1.25 μg) into the hind paw of rats resulted in a localized inflammatory hyperalgesia, as assessed by paw pressure (PP), paw immersion (PI), tail flick (TF) and hot plate (HP) tests.
ET injection resulted in a significant elevation in the levels of interleukin‐1β (IL‐1β) and nerve growth factor (NGF) in the injected foot as compared with the non‐injected foot. This increase was attenuated by intraperitoneal injections of dexamethasone (200 and 400 μg kg−1) and to a lesser extent by indomethacin (2 and 8 mg kg−1).
The tripeptide Lys‐D‐Pro‐Val, which is known to antagonize IL‐1β and prostaglandin E2 (PGE2) reversed mechanical hyperalgesia, as assessed by the PP test, and reduced significantly thermal hyperalgesia, as assessed by the HP and TF tests.
IL‐1ra reversed both mechanical (PP) and thermal (PI) nociceptive thresholds tested on the injected leg and significantly reduced thermal hyperalgesia, as assessed by the HP and TF tests.
A sheep, anti‐mouse NGF antiserum reversed mechanical hyperalgesia (PP test) but had little or no effect on thermal hyperalgesia (PI, HP and TF tests).
Our results indicate the importance of IL‐1β, NGF and prostaglandin E2 (PGE2) in the development of ET induced hyperalgesia and the possible existence of different mechanisms underlying thermal and mechanical as well as central and peripheral hyperalgesia.

British Journal of Pharmacology (1997) 121, 1619–1626; doi:10.1038/sj.bjp.0701313
Role of endothelin receptors, calcium and nitric oxide in the potentiation by endothelin‐1 of the sympathetic contraction of rabbit ear artery during cooling
Authors: García‐Villalón A. L. , Padilla J , Fernández N , Monge L , Gómez B , Diéguez G 
Published: August 2006

To examine further the potentiation by endothelin‐1 on the vascular response to sympathetic stimulation, we studied the isometric response of isolated segments, 2 mm long, from the rabbit central ear artery to electrical field stimulation (1–8 Hz), under different conditions, at 37°C and during cooling (30°C).
Electrical stimulation produced frequency‐dependent contraction, which was reduced (about 63% for 8 Hz) during cooling. At 30°C, but not at 37°C, endothelin‐1 (1, 3 and 10 nM) potentiated the contraction to electrical stimulation in a dose‐dependent way (from 43±7% to 190±25% for 8 Hz).
This potentiation by endothelin‐1 was reduced by the antagonist for endothelin ETA receptors BQ‐123 (10 μM) but not by the antagonist for endothelin ETB receptors BQ‐788 (10 μM). The agonist for endothelin ETB receptors IRL‐1620 (0.1 μM) did not modify the contraction to electrical stimulation.
The blocker of L‐type Ca2+ channels verapamil (10 μM l−1) reduced (about 72% for 8 Hz) and the unspecific blocker of Ca2+‐channels NiCl2 (1 mM) practically abolished (about 98%), the potentiating effects of endothelin‐1 found at 30°C.
Inhibition of nitric oxide synthesis with NG‐nitro‐L‐arginine (L‐NOARG, 0.1 mM) increased the contraction to electrical stimulation at 30°C more than at 37°C (for 8 Hz, this increment was 297±118% at 30°C, and 66±15% at 37°C). Endothelium removal increased the contraction to electrical stimulation at 30°C (about 91% for 8 Hz) but not at 37°C. Both L‐NOARG and endothelium removal abolished the potentiating effects of endothelin‐1 on the response to electrical stimulation found at 30°C.
These results in the rabbit ear artery suggest that during cooling, endothelin‐1 potentiates the contraction to sympathetic stimulation, which could be mediated at least in part by increasing Ca2+ entry after activation of endothelin ETA receptors. This potentiating effect of endothelin‐1 may require the presence of an inhibitory tone due to endothelial nitric oxide.

British Journal of Pharmacology (1997) 121, 1659–1664; doi:10.1038/sj.bjp.0701324
The effects of neuroleptic and tricyclic compounds on BKCa channel activity in rat isolated cortical neurones
Authors: Lee K , McKenna F , Rowe I. C. M. , Ashford M. L. J. 
Published: August 2006

The actions of several neuroleptic and tricyclic compounds were examined on the large conductance Ca2+‐activated K+ (BKCa) channel present in neurones isolated from the rat motor cortex.
Classical neuroleptic compounds including chlorpromazine and haloperidol applied to the intracellular surface of inside‐out patches produced a concentration‐dependent reduction in BKCa channel activity. Similar effects were observed when these compounds were applied to the extracellular surface of outside‐out patches.
In contrast, the atypical neuroleptic compounds clozapine and sulpiride did not affect BKCa channel activity (100 nM–1 mM) in either inside‐out or outside‐out patches, while 10 μM pimozide produced 73% of the inhibition produced by 10 μM chlorpromazine.
BKCa channel activity was also unaffected by application of structurally related tricyclic compounds including the anti‐cholinesterase tacrine and the anti‐epileptic carbamazepine. The tricyclic antidepressant drug amitriptyline was found to inhibit BKCa channel activity but was much less effective than the classical neuroleptic compounds.
It is concluded that compounds belonging to the classical neuroleptic group of drugs inhibit BKCa channel activity in the rat motor cortex in a structurally‐specific manner. This observation may be of clinical significance as it may contribute to some of the side effects associated with classical neuroleptic drug therapy.

British Journal of Pharmacology (1997) 121, 1810–1816; doi:10.1038/sj.bjp.0701333
Intrarenal haemodynamics and renal dysfunction in endotoxaemia: effects of nitric oxide synthase inhibition
Authors: Millar Colin G M. , Thiemermann Christoph 
Published: August 2006

This study investigated the effects of low dose endotoxin (lipopolysaccharide, LPS) on (i) systemic haemodynamics, (ii) renal blood flow (RBF), (iii) renal cortical and medullary perfusion and (iv) renal function in the anaesthetized rat. We have also investigated the effects of nitric oxide (NO) synthase (NOS) inhibition with NG‐methyl‐L‐arginine (L‐NMMA) on the alterations in systemic and renal haemodynamics and renal function caused by endotoxin.
Infusion of low dose LPS (1 mg kg−1 over 30 min, n=6) caused a late fall in mean arterial blood pressure (MAP, at 5 and 6 h after LPS), but did not cause an early (at 1–4 h after LPS) hypotension. The pressor effect of noradrenaline (NA, 1 μg kg−1, i.v.) was significantly reduced at 1 to 6 h after LPS (vascular hyporeactivity). Infusion of L‐NMMA (50 μg kg−1 min−1 commencing 60 min before LPS and continued throughout the experiment, n=7) abolished the delayed hypotension and significantly attenuated the vascular hyporeactivity to NA (at 2–6 h).
Infusion of LPS (1 mg kg−1 over 30 min, n=6) caused a rapid (within 2 h) decline in renal function (measured by inulin clearance) in the absence of a significant fall in MAP or renal blood flow (RBF). L‐NMMA (n=7) attenuated the impairment in renal function caused by LPS so that the inulin clearance in LPS‐rats treated with L‐NMMA was significantly greater than in LPS‐rats treated with vehicle (control) at 3–6 h after infusion of LPS.
Endotoxaemia also caused a significant reduction in renal cortical, but not medullary perfusion (measured as Laser Doppler flux). Infusion of L‐NMMA caused a significant further fall in cortical perfusion and a significant fall in medullary perfusion in the absence of changes in RBF.
Infusion of LPS resulted in a progressive increase in the plasma levels of nitrite/nitrate (an indicator of the formation of NO), so that the plasma concentration of nitrite/nitrate was significantly higher than baseline at 150 to 330 min after LPS. Infusion of L‐NMMA attenuated the rise in the plasma concentration of nitrite/nitrate (at 270 and 330 min, P<0.05) caused by LPS.
Thus, the renal dysfunction caused by injection of low dose of endotoxin in the rat occurs in the absence of significant falls in blood pressure or total renal blood flow. Inhibition of NOS activity with L‐NMMA attenuates the renal dysfunction caused by endotoxin (without improving intrarenal haemodynamics), suggesting that an overproduction of NO may contribute to the development of renal injury and dysfunction by causing direct cytotoxic effects.

British Journal of Pharmacology (1997) 121, 1824–1830; doi:10.1038/sj.bjp.0701335
Analysis of Risk Factors for Sternal Surgical Site Infection Emphasizing the Appropriate Ventilation of the Operating Theaters
Authors: Yavuz Serap Simsek , Bicer Yesim , Yapici Nihan , Kalaca Sibel , Aydin Osman Ozcan , Camur Gercek , Kocak Funda , Aykac Zuhal 
Published: August 2006

Objective.To determine the incidence of and identify risk factors for sternal surgical site infection (SSI).Design.Prospective cohort study. Data on potential risk factors, including the type of operating theater and infection data, were collected prospectively and analyzed by multivariate analysis.Setting.Siyami Ersek Thoracic and Cardiovascular Surgery Hospital, a 700-bed teaching hospital and the largest center for cardiac surgery in Turkey. The cardiothoracic unit performs approximately 3,000 cardiac operations per year.Patients.All adult patients who underwent cardiac surgery with sternotomy between January 14, 2002, and July 1, 2002, and who survived at least 4 days after surgery were included in the study.Results.Potential risk factor data were complete for 991 patients. There was sternal SSI in 41 patients (4.1%). Female sex, diabetes mellitus, operation performed in the older operating theaters, and duration of procedure exceeding 5 hours were identified as independent risk factors for sternal SSI.Conclusions.Female and diabetic patients are at higher risk for sternal SSI and should be followed up carefully after cardiac surgery to prevent the development of sternal SSI. Reducing the duration of surgery could reduce the rate of postoperative sternal SSI. The operating theater environment may have an important role in the pathogenesis of sternal SSI, and appropriate ventilation of the operating theaters would be critical in the prevention of sternal SSI.
Descriptive Epidemiology and Case-Control Study of Patients Colonized With Vancomycin-Resistant Enterococcus and Methicillin-ResistantStaphylococcus aureus
Authors: Sigurdardottir Bryndis , Berg Jeffery Vande , Hu Jianfang , Alamu Josiah , McNutt Louise-Anne , Diekema Daniel J. , Herwaldt Loreen A. 
Published: August 2006

Background.Patients colonized or infected with vancomycin-resistant enterococcus and methicillin-resistantStaphylococcus aureusmay be at risk of acquiring vancomycin-resistantS. aureusif the vanA gene is transferred from vancomycin-resistant enterococcus to methicillin-resistantS. aureus..Objective.Our goal was to identify risk factors for cocolonization or coinfection (CC/CI) with vancomycin-resistant enterococcus and methicillin-resistantS. aureus.Design.We conducted a descriptive, epidemiologic study of all patients with CC/CI identified from January 1998 to May 2003 and a nested case-control study of a cohort of patients hospitalized in the burn and wound unit.Setting.We conducted our study in a 813-bed tertiary care university teaching hospital.Population.The study population consisted of patients found to have CC/CI during the study period.Methods.Descriptive epidemiologic data were collected from hospital records of all patients identified as having CC/CI. A subset of patients hospitalized in the burn and wound unit were included in a case-control study.Results.CC/CI was detected in 71% of the patients during a single hospital stay. The burn and wound unit, which does active surveillance for both organisms, and the general medicine unit, which does not do active surveillance for either organism, cared for more than one-half of these patients. Among patients being cared for in the burn and wound unit, having exposure to 2 or more invasive devices (central venous catheters, indwelling urinary catheters, and enteral feeding tubes) and renal insufficiency were independent risk factors for CC/CI.Conclusions.Patients with CC/CI are the population at greatest risk for vancomycin-resistantS. aureuscolonization or infection. The number of invasive devices to which patients are exposed and, thus, possibly the patients' underlying severity of illness, as well as renal insufficiency, appear to be risk factors for CC/CI.
Risk Factors for Recovery of Imipenem- or Ceftazidime-Resistant Pseudomonas aeruginosa Among Patients Admitted to a Teaching Hospital in Brazil
Authors: Fortaleza Carlos Magno C. B. , Freire Maristela P. , Filho Djalma de C. Moreira , Ramos Marcelo de Carvalho 
Published: August 2006

Background.The prevalence of resistance to imipenem and ceftazidime among Pseudomonas aeruginosa isolates is increasing worldwide.Objective.Risk factors for nosocomial recovery (defined as the finding of culture-positive isolates after hospital admission) of imipenem-resistant P. aeruginosa (IRPA) and ceftazidime-resistant P. aeruginosa (CRPA) were determined.Design.Two separate case-control studies were conducted. Control subjects were matched to case patients (ratio, 2:1) on the basis of admission to the same ward at the same time as the case patient. Variables investigated included demographic characteristics, comorbid conditions, and the classes of antimicrobials used.Setting.The study was conducted in a 400-bed general teaching hospital in Campinas, Brazil that has 14,500 admissions per year. Case patients and control subjects were selected from persons who were admitted to the hospital during 1992–2002.Results.IRPA and CRPA isolates were obtained from 108 and 55 patients, respectively. Statistically significant risk factors for acquisition of IRPA were previous admission to another hospital (odds ratio [OR],4.21 [95% confidence interval {CI}, 1.40-12.66];P = .01), hemodialysis (OR, 7.79 [95% CI, 1.59-38.16]; P = .01), and therapy with imipenem (OR, 18.51 [95% CI, 6.30-54.43]; P<.001), amikacin (OR, 3.22 [95% CI, 1.40-7.41]; P = .005), and/or vancomycin (OR, 2.48 [95% CI, 1.08-5.64]; P = .03). Risk factors for recovery of CRPA were previous admission to another hospital (OR, 18.69 [95% CI, 2.00-174.28]; P = .01) and amikacin use (OR, 3.69 [95% CI, 1.32-10.35]; P = .01).Conclusion.Our study suggests a definite role for several classes of antimicrobials as risk factors for recovery of IRPA but not for recovery of CRPA. Limiting the use of only imipenem and ceftazidime may not be a wise strategy to contain the spread of resistant P. aeruginosa strains.
Retrospective Analysis of Catheter-Related Infections in a Hemodialysis Unit
Authors: Colville Linda A. , Lee Andy H. 
Published: August 2006

Objective.To compare the incidence rates of catheter-related bloodstream infection associated with different vascular access methods in patients receiving hemodialysis.Setting.Tertiary care public hospital in Western Australia.Design.Retrospective analysis of surveillance data collected by the hospital's infection control department.Methods.The number of confirmed bloodstream infections for each type of vascular access was identified for the period from July 2002 through June 2003. The corresponding number of patient-days was determined to calculate the infection incidence rates. The serially correlated data were then analyzed using Poisson generalized estimating equations.Results.A total of 32 confirmed bloodstream infections were identified. Infection rates, in number of infections per 1,000 patient-days, were as follows: 0.4 for native arteriovenous fistulae; 2.86 for synthetic arteriovenous grafts; 4.02 for permanent, tunneled, cuffed central venous catheters; and 20.2 for temporary, nontunneled, noncuffed central venous catheters. Compared with permanent catheters, the monthly infection rate associated with the temporary catheters was significantly higher (incident rate ratio [IRR], 5.025 [95% confidence interval {CI}, 1.532-16.484]; P = .008) and that of arteriovenous fistulae was significantly lower (IRR, 0.099 [95% CI, 0.030-0.324]; P = .001). The monthly infection rate for arteriovenous grafts was not significantly different from that for permanent central venous catheters (IRR, 0.702 [95% CI, 0.246-2.008]; P = .510).Conclusions.A hierarchy of infection risk associated with vascular access type is evident. Native arteriovenous fistulae should be recommended for all patients receiving chronic hemodialysis, to minimize infection.
Vegetation of Kilimanjaro: hidden endemics and missing bamboo
Authors: Hemp Andreas 
Published: August 2006

AbstractKilimanjaro has a large variety of forest types over an altitudinal range of 3000 m containing over 1200 vascular plant species. MontaneOcoteaforests occur on the wet southern slope.CassipoureaandJuniperusforests grow on the dry northern slope. SubalpineEricaforests at 4100 m represent the highest elevation cloud forests in Africa. In contrast to this enormous biodiversity, the degree of endemism is low. However, forest relicts in the deepest valleys of the cultivated lower areas suggest that a rich forest flora inhabited Mt Kilimanjaro in the past, with restricted‐range species otherwise only known from the Eastern Arc mountains. The low degree of endemism on Kilimanjaro may result from destruction of lower altitude forest rather than the relatively young age of the mountain. Another feature of the forests of Kilimanjaro is the absence of a bamboo zone, which occurs on all other tall mountains in East Africa with a similarly high rainfall.Sinarundinaria alpinastands are favoured by elephants and buffaloes. On Kilimanjaro these megaherbivores occur on the northern slopes, where it is too dry for a large bamboo zone to develop. They are excluded from the wet southern slope forests by topography and humans, who have cultivated the foothills for at least 2000 years. This interplay of biotic and abiotic factors could explain not only the lack of a bamboo zone on Kilimanjaro but also offers possible explanations for the patterns of diversity and endemism. Kilimanjaro's forests can therefore serve as a striking example of the large and long‐lasting influence of both animals and humans on the African landscape.
Relevance of neutrophils in the murine model of haemolytic uraemic syndrome: mechanisms involved in Shiga toxin type 2-induced neutrophilia
Authors: Fernandez G C , Lopez M F , Gomez S A , Ramos M V , Bentancor L V , Fernandez-Brando R J , Landoni V I , Dran G I , Meiss R , Isturiz M A , Palermo M S 
Published: August 2006

SummaryIt has been demonstrated that infections due to Shiga toxins (Stx) producing Escherichia coli are the main cause of the haemolytic uraemic syndrome (HUS). However, the contribution of the inflammatory response in the pathogenesis of the disease has also been well established. Neutrophils (PMN) represent a central component of inflammation during infections, and patients with high peripheral PMN counts at presentation have a poor prognosis. The mouse model of HUS, by intravenous injection of pure Stx type 2 (Stx2), reproduces human neutrophilia and allows the study of early events in the course of Stx2-induced pathophysiological mechanisms. The aim of this study was to address the contribution of PMN on Stx2 toxicity in a murine model of HUS, by evaluating the survival and renal damage in mice in which the granulocytic population was depleted. We found that the absence of PMN reduced Stx2-induced lethal effects and renal damage. We also investigated the mechanisms underlying Stx2-induced neutrophilia, studying the influence of Stx2 on myelopoyesis, on the emergence of cells from the bone marrow and on the in vivo migration into tissues. Stx2 administration led to an accelerated release of bone marrow cells, which egress at an earlier stage of maturation, together with an increase in the proliferation of myeloid progenitors. Moreover, Stx2-treated mice exhibited a lower migratory capacity to a local inflammatory site. In conclusion, PMN are essential in the pathogenesis of HUS and neutrophilia is not merely an epiphenomenon, but contributes to Stx2-damaging mechanism by potentiating Stx2 toxicity.
Activated T lymphocytes suppress osteoclastogenesis by diverting early monocyte/macrophage progenitor lineage commitment towards dendritic cell differentiation through down-regulation of receptor activator of nuclear factor-kappaB and c-Fos
Authors: Grčević D , Lukić I K , Kovačić N , Ivčević S , Katavić V , Marušić A 
Published: August 2006

SummaryActivated T lymphocytes either stimulate or inhibit osteoclastogenesis from haematopoietic progenitors in different experimental models. To address this controversy, we used several modes of T lymphocyte activation in osteoclast differentiation − mitogen-pulse, anti-CD3/CD28 stimulation and in vivo and in vitro alloactivation. Osteoclast-like cells were generated from non-adherent immature haematopoietic monocyte/macrophage progenitors in murine bone-marrow in the presence of receptor activator of nuclear factor (NF)-κB ligand (RANKL) and monocyte–macrophage colony-stimulating factor (M-CSF). All modes of in vivo and in vitro T lymphocyte activation and both CD4+ and CD8+ subpopulations produced similar inhibitory effects on osteoclastogenesis paralleled by enhanced dendritic cell (DC) differentiation. Osteoclast-inhibitory effect was associated with T lymphocyte activation and not proliferation, and could be replaced by their culture supernatants. The stage of osteoclast differentiation was crucial for the inhibitory action of activated T lymphocytes on osteoclastogenesis, because the suppressive effect was visible only on early osteoclast progenitors but not on committed osteoclasts. Inhibition was associated specifically with increased granulocyte–macrophage colony-stimulating factor (GM-CSF) expression by the mechanism of progenitor commitment toward lineages other than osteoclast because activated T lymphocytes down-regulated RANK, CD115, c-Fos and calcitonin receptor expression, and increased differentiation towards CD11c-positive DC. An activated T lymphocyte inhibitory role in osteoclastogenesis, confirmed in vitro and in vivo, mediated through GM-CSF release, may be used to counteract activated bone resorption mediated by T lymphocyte-derived cytokines in inflammatory and immune disorders. We also demonstrated the importance of alloactivation in osteoclast differentiation and the ability of cyclosporin A to abrogate T lymphocyte inhibition of osteoclastogenesis, thereby confirming the functional link between alloreaction and bone metabolism.