bluuebunny/crossref_metadata_2025_split huggingface dataset:
Substance P and glutamate receptor antagonists improve the anti‐arthritic actions of dexamethasone in rats
Authors: Lam Francis FY , Ng Ethel SK 
Published: January 2010

Background and purpose:  Current single drug treatments for rheumatoid arthritis have problems of limited efficacy and/or high toxicity. This study investigates the benefits of individual and combined treatments with dexamethasone and substance P and glutamate receptor antagonists in a rat model of arthritis.Experimental approach:  Arthritis was induced in rats by unilateral intra‐articular injection of Freund's complete adjuvant. Separate groups of rats were subjected to the following treatments 15 min before induction of arthritis: (i) control with no drug treatment; (ii) single intra‐articular injection of a NK1 receptor antagonist RP67580; (iii) single intra‐articular injection of a NMDA receptor antagonist AP7 plus a non‐NMDA receptor antagonist CNQX; (iv) daily oral dexamethasone; and (v) combined treatment with dexamethasone and all of the above receptor antagonists. Knee joint allodynia, swelling, hyperaemia and histological changes were examined over a period of 7 days.Key results:  Treatment with dexamethasone suppressed joint swelling, hyperaemia and histological changes that include polymorphonuclear cell infiltration, synovial tissue proliferation and cartilage erosion in the arthritic rat knees. Treatment with RP67580 or AP7 plus CNQX did not attenuate hyperaemia or histological changes, but reduced joint allodynia and swelling. Co‐administration of dexamethasone with these receptor antagonists produced greater inhibition on joint allodynia and swelling than their individual effects.Conclusions and implications:  The data suggest substance P and glutamate contribute to arthritic pain and joint swelling. The efficacy of dexamethasone in reducing arthritic pain and joint swelling can be improved by co‐administration of substance P and glutamate receptor antagonists.
Cannabidiol ameliorates cognitive and motor impairments in bile‐duct ligated mice via 5‐HT1A receptor activation
Authors: Magen I , Avraham Y , Ackerman Z , Vorobiev L , Mechoulam R , Berry EM 
Published: January 2010

Background and purpose:  We aimed to demonstrate the involvement of 5‐HT1A receptors in the therapeutic effect of cannabidiol, a non‐psychoactive constituent of Cannabis sativa, in a model of hepatic encephalopathy induced by bile‐duct ligation (BDL) in mice.Experimental approach:  Cannabidiol (5 mg·kg−1; i.p.) was administered over 4 weeks to BDL mice. Cognition and locomotion were evaluated using the eight‐arm maze and the open field tests respectively. Hippocampi were analysed by RT‐PCR for expression of the genes for tumour necrosis factor‐α receptor 1, brain‐derived neurotrophic factor (BDNF) and 5‐HT1A receptor. N‐(2‐(4‐(2‐methoxy‐phenyl)‐1‐piperazin‐1‐yl)ethyl)‐N‐(2‐pyridyl) cyclohexanecarboxamide (WAY‐100635), a 5‐HT1A receptor antagonist (0.5 mg·kg−1), was co‐administered with cannabidiol. Liver function was evaluated by measuring plasma liver enzymes and bilirubin.Key results:  Cannabidiol improved cognition and locomotion, which were impaired by BDL, and restored hippocampal expression of the tumour necrosis factor‐α receptor 1 and the BDNF genes, which increased and decreased, respectively, following BDL. It did not affect reduced 5‐HT1A expression in BDL mice. All the effects of cannabidiol, except for that on BDNF expression, were blocked by WAY‐100635, indicating 5‐HT1A receptor involvement in cannabidiol's effects. Cannabidiol did not affect the impaired liver function in BDL.Conclusions and implications:  The behavioural outcomes of BDL result from both 5‐HT1A receptor down‐regulation and neuroinflammation. Cannabidiol reverses these effects through a combination of anti‐inflammatory activity and activation of this receptor, leading to improvement of the neurological deficits without affecting 5‐HT1A receptor expression or liver function. BDNF up‐regulation by cannabidiol does not seem to account for the cognitive improvement.
Circadian Activity Rhythms and Mortality: The Study of Osteoporotic Fractures
Authors: Tranah Gregory J. , Blackwell Terri , Ancoli‐Israel Sonia , Paudel Misti L. , Ensrud Kristine E. , Cauley Jane A. , Redline Susan , Hillier Teresa A. , Cummings Steven R. , Stone Katie L. ,   for the Study of Osteoporotic Fractures Research Group
Published: January 2010

OBJECTIVES: To determine whether circadian activity rhythms are associated with mortality in community‐dwelling older women.DESIGN: Prospective study of mortality.SETTING: A cohort study of health and aging.PARTICIPANTS: Three thousand twenty‐seven community‐dwelling women from the Study of Osteoporotic Fractures cohort (mean age 84).MEASUREMENTS: Activity data were collected using wrist actigraphy for a minimum of three 24‐hour periods, and circadian activity rhythms were computed. Parameters of interest included height of activity peak (amplitude), midline estimating statistic of rhythm (mesor), strength of activity rhythm (robustness), and time of peak activity (acrophase). Vital status, with cause of death adjudicated through death certificates, was prospectively ascertained.RESULTS: Over an average of 4.1 years of follow‐up, there were 444 (14.7%) deaths. There was an inverse association between peak activity height and all‐cause mortality rates, with higher mortality rates observed in the lowest activity quartile (hazard ratio (HR)=2.18, 95% confidence interval (CI)=1.63–2.92) than in the highest quartile after adjusting for age, clinic site, race, body mass index, cognitive function, exercise, instrumental activity of daily living impairments, depression, medications, alcohol, smoking, self‐reported health status, married status, and comorbidities. A greater risk of mortality from all causes was observed for those in the lowest quartiles of mesor (HR=1.71, 95% CI=1.29–2.27) and rhythm robustness (HR=1.97, 95% CI=1.50–2.60) than for those in the highest quartiles. Greater mortality from cancer (HR=2.09, 95% CI=1.04–4.22) and stroke (HR=2.64, 95% CI=1.11–6.30) was observed for later peak activity (after 4:33 p.m.; >1.5 SD from mean) than for the mean peak range (2:50–4:33 p.m.).CONCLUSION: Older women with weak circadian activity rhythms have higher mortality risk. If confirmed in other cohorts, studies will be needed to test whether interventions (e.g., physical activity, bright light exposure) that regulate circadian activity rhythms will improve health outcomes in older adults.
Prevalence of Psychiatric Illnesses in Older Ethnic Minority Adults
Authors: Jimenez Daniel E. , Alegría Margarita , Chen Chih‐nan , Chan Domin , Laderman Mara 
Published: January 2010

OBJECTIVES: To compare lifetime and 12‐month prevalence of psychiatric disorders in a nationally representative sample of older Latino, Asian, African‐American, and Afro‐Caribbean adults with that of older non‐Latino white adults.DESIGN: Cross‐sectional study conducted in 2001 through 2004.SETTING: Urban and rural households in the contiguous United States.PARTICIPANTS: Two thousand three hundred seventy‐five community‐dwelling residents aged 60 and older living in noninstitutional settings. Data are from the National Institutes of Mental Health Collaborative Psychiatric Epidemiological Studies.METHODS: The World Mental Health Composite International Diagnostic Interview assessed lifetime and 12‐month psychiatric disorders. Bayesian estimates compared psychiatric disorder prevalence rates of ethnic and racial groups.RESULTS: Older non‐Latino whites exhibited a greater prevalence on several lifetime diagnoses than older Asian, African‐American, and Afro‐Caribbean respondents. Older Latinos did not differ from older non‐Latino whites on any lifetime diagnosis and had higher 12‐month rates of any depressive disorder. No differences were observed in the 12‐month diagnoses between older non‐Latino whites and the other racial and ethnic minority groups. Older immigrant Latinos had higher lifetime rates of dysthymia and generalized anxiety disorder (GAD) than U.S.‐born Latinos. Older immigrant Asians had higher lifetime rates of GAD than U.S.‐born Asians. Older immigrant Latinos had higher 12‐month rates of dysthymia than older U.S.‐born Latinos.CONCLUSION: Caution should be taken when generalizing the protective effects of ethnicity into old age. Older Asians and African‐Americans exhibited lower prevalence rates of some psychiatric disorders, whereas older Latinos exhibited rates equal to those of older non‐Latino whites. Also, the protective effect of nativity seems to vary according to age, psychiatric disorder, and ethnicity.
An Increase in Endothelial Intracellular Calcium and F‐Actin Precedes the Extravasation of Interleukin‐2‐Activated Lymphocytes
Authors: EHRINGER WILLIAM D. , EDWARDS MICHAEL J. , WINTERGERST KUPPER A. , COX ABIGAIL , MILLER FREDERICK N. 
Published: January 2010

ABSTRACTObjective: Interleukin‐2 (IL‐2) induces protein leakage from the microcirculation and activates lymphocytes; yet it is unclear how it alters endothelial barrier function. Here, we report of a new continuous monitoring system that allows for the continuous measurement and correlation of endothelial calcium, permeability to albumin, and extravasation of lymphocytes.Methods: IL‐2 activated lymphocytes (IL‐2 LYMPH) or unstimulated lymphocytes (LYMPH) were co‐incubated with human microvascular endothelial cells (HMVEC). Endothelial albumin permeability, lymphocyte extravasation, intracellular calcium mobilization, and f‐actin distribution were examined using a new continuous monitoring system.Results: The clearance rate of fluorescein isothiocyanate‐labeled‐human serum albumin (FITC‐HSA) in the presence of IL‐2 LYMPH peaked at 20 minutes, whereas the clearance rate of LYMPH peaked at 40 minutes. Approximately 40 minutes after the peak in the clearance rate to albumin, extravasation of carboxyfluorescein‐labeled lymphocytes was detected. Peak clearance rates for the extravasation of IL‐2 LYMPH occurred at approximately 40 minutes after the addition of the lymphocytes to the HMVEC, whereas the peak clearance rate for the LYMPH occurred at 60 minutes after their addition. Both FITC‐HSA and lymphocyte extravasation were measured concurrent to endothelial intracellular calcium mobilization by FURA‐2. There was an increase in calcium activation after the addition of IL‐2 stimulated lymphocytes (71 ± 5.1 nmol/L to 185 ± 18.9 nmol/L) compared with unstimulated lymphocytes (71 ± 5.1 nmol/L to 110 ± 12.2 nmol/L). The addition of IL‐2 had little or no effect on endothelial actin, whereas the unstimulated lymphocytes and, to a greater extent, IL‐2 LYMPH increased the presence of transversing stress fibers and decreased peripheral actin.Conclusions: The findings reported here suggest that the permeability and extravasation events that occur upon addition of lymphocytes proceeds by a calcium‐ and actin‐dependent mechanism and that incubation of lymphocytes with IL‐2 enhances normal lymphocyte mechanisms of extravasation.
Life and Death in the Microcirculation: a Role for Angiotensin II
Authors: GREENE ANDREW S. 
Published: January 2010

ABSTRACTObjective: Angoitensin II (ANGII) plays a critical role in the maintenance of the microcirculation and in the anatomical loss of microvessels (rarefaction) that occurs in low renin forms of hypertension and in animals fed a high‐salt diet. Elevations in sodium intake can trigger a series of hemodynamic and hormonal responses culminating in a substantial rarefaction of small arterioles and capillaries in both normal and reduced renal mass hypertensive rats.Methods: Immunohistochemistry, Northern blot, and reverse transcription‐polymerase chain reaction (RT‐PCR) analysis of microdissected blood vessels were used to localize ANGII receptors in the microcirculation. Chronic infusion of ANGII and other physiologic and pharmacologic manipulations of the renin‐angiotensin system in rats was combined with morphologic and mathematical analysis of the network architecture.Results: We have shown that rarefaction of the microcirculation can cause an increase in total peripheral resistance, reduced tissue perfusion, decreased oxygen delivery, and impaired organ function. Although the mechanisms by which this occurs are not well understood, a number of key observations point to a role for the renin‐angiotensin system in this effect. First, ANGII infused systemically at subpressor levels, or locally into the skeletal muscle interstitium, can induce significant microvessel growth. Second, localization of ANGII receptor proteins by immunohistochemistry and Western blotting and RNA localization by RT‐PCR confirm the presence of AT1receptors, which are growth‐stimulatory, and AT2receptors, which are growth‐inhibitory in the microcirculation. Third, maintenance of ANGII at normal levels during periods of hypertension or high‐salt diet completely eliminates rarefaction.Conclusions: Taken together, these results support the hypothesis that ANGII acting through AT1‐ and AT2‐receptor mechanisms modulate vessel density during high‐salt diet and hypertension.
Vascular Endothelial Growth Factor and Microvascular Permeability
Authors: BATES DAVID O. , LODWICK DAVID , WILLIAMS BRYAN 
Published: January 2010

ABSTRACTVascular Endothelial Growth Factors (VEGFs) are endogenously produced vascular cytokines which result in angiogenesis, vasodilatation, and increased microvascular permeabilityin vivo. They are endothelial specific and result in mitosis, migration, stress fiber formation and increased permeability of endothelial cells in culture. They have been critically implicated in a host of pathological conditions including solid tumor growth and diabetes, and been proposed as a therapy for coronary and peripheral ischemic disease. However, the potent permeability‐enhancing properties of VEGFs are very poorly understood. The pharmacology, signal transduction pathways, intracellular signaling mechanisms, and ultrastructural changes which result in increased permeability are still not clear. This review discusses the available evidence for how VEGFs increase permeabilityin vivo, and some of the pitfalls in interpreting experiments which do not take into account the vasoactive properties of VEGFs. It also discusses the clinical implications of the permeability enhancing effect of VEGFs, and the relevance of these studies to development of new therapies.
Microcirculatory Dysfunction Induced by Cigarette Smoking
Authors: LEHR HANS‐ANTON 
Published: January 2010

ABSTRACTThis review deals with the deleterious effects of cigarette smoking on the microcirculation, both in terms of morphological (i.e., vessel wall injury, capillary loss) and functional aspects. The latter concerns predominantly changes in tissue perfusion and its regulatory mechanisms (i.e., reactive hyperemia, sequestration of blood cells in the microcirculation). The mechanisms of action of cigarette smoking on the microcirculation include compromised endothelial‐dependent vasorelaxation, platelet aggregation, endothelial cell dysfunction, and the activation of circulating leukocytes. Through these mechanisms, cigarette smoking elicits the aggregation and adhesion of leukocytes and/or platelets to the microvascular endothelium in venules and arterioles, as assessed by intravital fluorescence microscopy in the hamster skinfold chamber model. This model has allowed us to learn more about the participation of reactive oxygen species, inflammatory mediators, and adhesion molecules in the orchestration of microcirculatory dysfunction after cigarette smoking. In the final part of this review, the clinical consequences of microcirculatory dysfunction are discussed and an outlook is offered on potential prophylactic interventions (i.e., antioxidant vitamins) aimed at abrogating the deleterious action of cigarette smoking on the microcirculation.Microcirculation (2000) 7, 367–384.
The Peritoneal Microcirculation in Peritoneal Dialysis
Authors: RIPPE BENGT , ROSENGREN BERT‐INGE , VENTUROLI DANIELE 
Published: January 2010

ABSTRACTThis paper deals with the peritoneal microcirculation and with peritoneal exchange occurring in peritoneal dialysis (PD). The capillary wall is a major barrier to solute and water exchange across the peritoneal membrane. There is a bimodal size‐selectivity of solute transport between blood and the peritoneal cavity, through pores of radius ∼40–50 Å as well as through a very low number of large pores of radius ∼250 Å. Furthermore, during glucose‐induced osmosis during PD, nearly 40% of the total osmotic water flow occurs through molecular water channels, termed “aquaporin‐1.” This causes an inequality between 1−σ and the sieving coefficient for small solutes, which is a key feature of the “threepore model” of peritoneal transport. The peritoneal interstitium, coupled in series with the capillary walls, markedly modifies small‐solute transport and makes large‐solute transport asymmetric. Thus, although severely restricted in the blood‐to‐peritoneal direction, the absorption of large solutes from the peritoneal cavity occurs at a high clearance rate (∼1 mL/min), largely independent of molecular radius. True absorption of macromolecules to the blood via lymphatics, however, seems to be occurring at a rate of ∼0.2 mL/min. Several controversial issues regarding transcapillary and transperitoneal exchange mechanisms are discussed in this paper.
Variable expression of tenascin‐C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lung
Authors: KAARTEENAHO RIITTA , SORMUNEN RAIJA , PÄÄKKÖ PAAVO 
Published: January 2010

Kaarteenaho R, Sormunen R, Pääkkö P. Variable expression of tenascin‐C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lung. APMIS 2010; 118: 91–100.The aim of this study was to analyse the expression of tenascin‐C, osteopontin and fibronectin in inflammatory myofibroblastic tumour of the lung, which is a rare tumour of unknown aetiology. Nine patients with an inflammatory myofibroblastic tumour of lung were studied by immunohistochemistry for the presence of tenascin‐C, osteopontin, fibronectin and alpha‐smooth muscle actin, which is a common marker for myofibroblasts. The ultrastructure of myofibroblasts was confirmed by transmission electron microscopy. The expression of tenascin‐C, osteopontin, fibronectin and alpha‐smooth muscle actin was also studied by immunoelectron microscopy. All cases displayed all of the studied extracellular matrix proteins and also alpha‐smooth muscle actin‐positive spindle‐shaped fibroblastic cells that were undoubtedly myofibroblasts. The immunoelectron microscopic studies demonstrated labelling for alpha‐smooth muscle actin in intracellular filament bundles within myofibroblasts, for fibronectin in the extracellular filaments of the fibronexus and for tenascin‐C extracellularly often adjacent to myofibroblasts. Labels for osteopontin were observed within myofibroblasts and plasma cells. These results demonstrate that tenascin‐C, osteopontin and fibronectin were expressed in all three kinds of subtypes of inflammatory myofibroblastic tumours of the lung and further, variable amounts of myofibroblasts could be observed by light and transmission electron microscopy as well as by immunoelectron microscopic techniques.
Effect of renal and non‐renal ischemia/reperfusion on cell‐mediated immunity in organs and plasma
Authors: BRØCHNER ANNE C. , DAGNÆS‐HANSEN FREDERIK , TOFT PALLE 
Published: January 2010

Brøchner AC, Dagnæs‐Hansen F, Toft P. Effect of renal and non‐renal ischemia/reperfusion on cell‐mediated immunity in organs and plasma. APMIS 2010; 118: 101–7.Acute renal failure (ARF) is a common morbidity factor among patients in the intensive care unit, reaching an incidence from 3% to 30% depending on the definition of ARF and the population. Although the majority of the patients with ARF are treated with continuous renal replacement therapy, the mortality rate still remains above 50%. The causes of death are primarily extra‐renal and include infection, shock, septicemia, and respiratory failure. We wanted to evaluate the cell‐mediated inflammatory response of renal ischemia–reperfusion (I/R) and non‐renal I/R, in blood and in distant organs. In our study, 80 mice were divided into four groups. The following surgeries were performed on the groups compared: bilateral renal I/R by clamping, unilateral renal ischemia, anesthesia only, and unilateral hind leg I/R. Half of the animals were killed after 2 h and the other half after 24 h. To assess the inflammatory response, we measured myeloperoxidase (MPO) in the organs, and CD 11b and major histocompatibility complex (MHC) II‐positive cells in the blood. Non‐renal I/R elicited the most elevated levels of MPO in extra‐renal tissue such as the lungs. There was a trend toward higher MPO levels in the kidney following renal I/R. All kinds of I/R induced an upregulation of the adhesion molecule CD 11b and a downregulation of MHC II. Renal and non‐renal I/R induced neutrophil infiltration in distant organs. Renal I/R does not induce a larger cell‐mediated inflammatory response in blood and organs than non‐renal I/R.
Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells
Authors: BOSSETO MAIRA CEGATTI , PALMA PATRICIA VIANNA BONINI , COVAS DIMAS TADEU , GIORGIO SELMA 
Published: January 2010

Bosseto MC, Palma PVB, Covas DT, Giorgio S. Hypoxia modulates phenotype, inflammatory response, and leishmanial infection of human dendritic cells. APMIS 2010; 118: 108–14.Development of hypoxic areas occurs during infectious and inflammatory processes and dendritic cells (DCs) are involved in both innate and adaptive immunity in diseased tissues. Our group previously reported that macrophages exposed to hypoxia were infected with the intracellular parasiteLeishmania amazonensis, but showed reduced susceptibility to the parasite. This study shows that although hypoxia did not alter human DC viability, it significantly altered phenotypic and functional characteristics. The expression of CD1a, CD80, and CD86 was significantly reduced in DCs exposed to hypoxia, whereas CD11c, CD14, CD123, CD49 and HLA‐DR expression remained unaltered in DCs cultured in hypoxia or normoxia. DC secretion of IL‐12p70, the bioactive interleukin‐12 (IL‐12), a cytokine produced in response to inflammatory mediators, was enhanced under hypoxia. In addition, phagocytic activity (Leishmaniauptake) was not impaired under hypoxia, although this microenviroment induced infected DCs to reduce parasite survival, consequently controlling the infection rate. All these data support the notion that a hypoxic microenvironment promotes selective pressure on DCs to assume a phenotype characterized by pro‐inflammatory and microbial activities in injured or inflamed tissues and contribute to the innate immune response.