bluuebunny/crossref_metadata_2025_split huggingface dataset:
The adenosine A1receptor antagonist SLV320 reduces myocardial fibrosis in rats with 5/6 nephrectomy without affecting blood pressure
Authors: Kalk P , Eggert B , Relle K , Godes M , Heiden S , Sharkovska Y , Fischer Y , Ziegler D , Bielenberg G‐W , Hocher B 
Published: June 2007

Background and purpose:Myocardial fibrosis is an unwanted effect associated with chronic renal failure. The adenosine system is involved in cardiac and renal function. Therefore, we investigated the novel selective adenosine A1receptor antagonist SLV320 focusing on its potential in preventing cardiomyopathy in rats with 5/6 nephrectomy.Experimental approach:Male Sprague‐Dawley rats were allocated to 4 groups of 12 rats each: 5/6 nephrectomy (5/6 NX), 5/6 NX plus SLV320 (10 mg kg−1 d−1mixed with food), sham and sham plus SLV320. Study duration was 12 weeks, blood pressure was assessed repeatedly. At study end kidney function was assessed, blood samples and hearts were taken for histology/immunohistochemistry. Pharmacological properties of SLV320 were assessed using receptor binding and enzyme assays and in vivo.Key results:SLV320 is a selective and potent adenosine A1antagonistin vitro(Ki=1 nM) with a selectivity factor of at least 200 versus other adenosine receptor subtypes. Functional A1antagonism was demonstratedin vivo. In rats with 5/6 NX SLV320 significantly decreased albuminuria by about 50%, but did not alter glomerular filtration rate (GFR). SLV320 normalized cardiac collagen I+III contents in 5/6 NX rats. SLV320 prevented nephrectomy‐dependent rise in plasma levels of creatinine kinase (CK), ALT and AST. Blood pressure did not differ between study groups.Conclusion:SLV320 suppresses cardiac fibrosis and attenuates albuminuria without affecting blood pressure in rats with 5/6 nephrectomy, indicating that selective A1receptor antagonists may be beneficial in uraemic cardiomyopathy.British Journal of Pharmacology(2007)151, 1025–1032; doi:10.1038/sj.bjp.0707319
Virodhamine and CP55,940 modulate cAMP production and IL‐8 release in human bronchial epithelial cells
Authors: Gkoumassi E , Dekkers B G J , Dröge M J , Elzinga C R S , Schmidt M , Meurs H , Zaagsma J , Nelemans S A 
Published: June 2007

Background and purpose:We investigated expression of cannabinoid receptors and the effects of the endogenous cannabinoid virodhamine and the synthetic agonist CP55,940 on cAMP accumulation and interleukin‐8 (IL‐8) release in human bronchial epithelial cells.Experimental approach:Human bronchial epithelial (16HBE14o−) cells were used. Total mRNA was isolated and cannabinoid receptor mRNAs were detected by RT‐PCR. Expression of CB1and CB2receptor proteins was detected with Western blotting using receptor‐specific antibodies. cAMP accumulation was measured by competitive radioligand binding assay. IL‐8 release was measured by ELISA.Key results:CB1and CB2receptor mRNAs and proteins were found. Both agonists concentration‐dependently decreased forskolin‐induced cAMP accumulation. This effect was inhibited by the CB2receptor antagonist SR144528, and was sensitive toPertussistoxin (PTX), suggesting the involvement of CB2receptors and Gi/o‐proteins. Cell pretreatment with PTX unmasked a stimulatory component, which was blocked by the CB1receptor antagonist SR141716A. CB2receptor‐mediated inhibition of cAMP production by virodhamine and CP55,940 was paralleled by inhibition of tumor necrosis factor‐α (TNF‐α) induced IL‐8 release. This inhibition was insensitive to SR141716A. In the absence of agonist, SR144528 by itself reduced TNF‐α induced IL‐8 release.Conclusions and implications:Our results show for the first time that 16HBE14o−cells respond to virodhamine and CP55,940. CB1and CB2receptor subtypes mediated activation and inhibition of adenylyl cyclase, respectively. Stimulation of the dominant CB2receptor signalling pathway diminished cAMP accumulation and TNF‐α‐induced IL‐8 release. These observations may imply that cannabinoids exert anti‐inflammatory properties in airways by modulating cytokine release.British Journal of Pharmacology(2007)151, 1041–1048; doi:10.1038/sj.bjp.0707320
The effect of the palmitoylethanolamide analogue, palmitoylallylamide (L‐29) on pain behaviour in rodent models of neuropathy
Authors: Wallace V C J , Segerdahl A R , Lambert D M , Vandevoorde S , Blackbeard J , Pheby T , Hasnie F , Rice A S C 
Published: June 2007

Background and Purpose:Cannabinoids are associated with analgesia in acute and chronic pain states. A spectrum of central cannabinoid (CB1) receptor‐mediated motor and psychotropic side effects limit their therapeutic potential. Here, we investigate the analgesic effect of the palmitoylethanolamide (PEA) analogue, palmitoylallylamide (L‐29), which via inhibition of fatty acid amide hydrolase (FAAH) may potentiate endocannabinoids thereby avoiding psychotropic side effects.Experimental Approach:Thein vivoanalysis of the effect of L‐29 on measures of pain behaviour in three rat models of neuropathic pain.Key Results:Systemically administered L‐29 (10 mg kg−1) reduced hypersensitivity to mechanical and thermal stimuli in the partial sciatic nerve injury (PSNI) model of neuropathic pain; and mechanical hypersensitivity in a model of antiretroviral (ddC)‐associated hypersensitivity and a model of varicella zoster virus (VZV)‐associated hypersensitivity. The effects of L‐29 were comparable to those of gabapentin (50 mg kg−1). The CB1receptor antagonist SR141716a (1 mg kg−1) and the CB2receptor antagonist SR144528 (1 mg kg−1) reduced the effect of L‐29 on hypersensitivity in the PSNI and ddC models, but not in the VZV model. The peroxisome proliferator‐activated receptor‐α antagonist, MK‐886 (1 mg kg−1), partially attenuated the effect of L‐29 on hypersensitivity in the PSNI model. L‐29 (10 mg kg−1) significantly attenuated thigmotactic behaviour in the open field arena without effect on locomotor activity.Conclusions and Implications:L‐29 produces analgesia in a range of neuropathic pain models. This presents L‐29 as a novel analgesic compound that may target the endogenous cannabinoid system while avoiding undesirable side effects associated with direct cannabinoid receptor activation.British Journal of Pharmacology(2007)151, 1117–1128; doi:10.1038/sj.bjp.0707326
The second extracellular loop of α2A‐adrenoceptors contributes to the binding of yohimbine analogues
Authors: Laurila J M M , Xhaard H , Ruuskanen J O , Rantanen M J M , Karlsson H K , Johnson M S , Scheinin M 
Published: June 2007

Background and purpose:Rodent α2A‐adrenoceptors bind the classical α2‐antagonists yohimbine and rauwolscine with lower affinity than the human α2A‐adrenoceptor. A serine‐cysteine difference in the fifth transmembrane helix (TM; position 5.43) partially explains this, but all determinants of the interspecies binding selectivity are not known. Molecular models of α2A‐adrenoceptors suggest that the second extracellular loop (XL2) folds above the binding cavity and may participate in antagonist binding.Experimental approach:Amino acids facing the binding cavity were identified using molecular models: side chains of residues 5.43 in TM5 and xl2.49 and xl2.51 in XL2 differ between the mouse and human receptors. Reciprocal mutations were made in mouse and human α2A‐adrenoceptors at positions 5.43, xl2.49 and xl2.51, and tested with a set of thirteen chemically diverse ligands in competition binding assays.Key results:Reciprocal effects on the binding of yohimbine and rauwolscine in human and mouse α2A‐adrenoceptors were observed for mutations at 5.43, xl2.49 and xl2.51. The binding profile of RS‐79948‐197 was reversed only by the XL2 substitutions.Conclusions and implications:Positions 5.43, xl2.49 and xl2.51 are major determinants of the species preference for yohimbine and rauwolscine of the human versus mouse α2A‐adrenoceptors. Residues at positions xl2.49 and xl2.51 determine the binding preference of RS‐79948‐197 for the human α2A‐adrenoceptor. Thus, XL2 is involved in determining the species preferences of α2A‐adrenoceptors of human and mouse for some antagonists.British Journal of Pharmacology (2007) 151, 1293–1304; doi:10.1038/sj.bjp.0707330
Prevalence of Methicillin-ResistantStaphylococcus aureusColonization Among Older Residents of Care Homes in the United Kingdom
Authors: Barr Benjamin , Wilcox Mark H. , Brady Angela , Parnell Peter , Darby Bob , Tompkins David 
Published: June 2007

Objective.To determine the prevalence of methicillin-resistantStaphylococcus aureus(MRSA) colonization among older residents of care homes in Leeds, United Kingdom, and to identify resident and care home risk factors for carriage.Design.We conducted a cross-sectional prevalence survey of 715 residents from 39 care homes. All participants were tested for nasal colonization with S.aureus,including MRSA. A short questionnaire was completed about each participant and each care home. A multivariable model was used to determine which risk factors were independently associated with MRSA colonization.Setting.Care homes for older residents in Leeds, United Kingdom.Participants.All residents in participating homes who were able to give informed consent.Results.A total of 159 of 715 residents tested positive for MRSA, for a prevalence of 22% (95% confidence interval, 18%—27%) The resultant multivariate model showed that residence in a home with a low ratio of nurses to beds, residence in a care home in a deprived area, male sex, presence of an invasive device, and a hospitalization duration of more than 10 days during the previous 2 years were independently associated with MRSA colonization.Conclusions.This study found a large reservoir of MRSA within the care home population. Control strategies need to be coordinated between care homes and hospitals. Increasing the ratio of nurses to beds, reducing the duration of hospitalization, and improving the management of invasive devices could help reduce the prevalence of MRSA colonization. Further research is required to ascertain the potential health benefits of reducing the rate of MRSA colonization among care home residents.
Effectiveness of Multifaceted Hospitalwide Quality Improvement Programs Featuring an Intervention to Remove Unnecessary Urinary Catheters at a Tertiary Care Center in Thailand
Authors: Apisarnthanarak Anucha , Thongphubeth Kanokporn , Sirinvaravong Sirinaj , Kitkangvan Danai , Yuekyen Chananart , Warachan Boonyasit , Warren David K. , Fraser Victoria J. 
Published: June 2007

Objective.To evaluate the efficacy of a multifaceted hospitalwide quality improvement program that featured an intervention to remind physicians to remove unnecessary urinary catheters.Methods.A hospitalwide preintervention-postintervention study was conducted over 2 years (July 1, 2004, through June 30, 2006). The intervention consisted of nurse-generated daily reminders that were used by an intervention team to remind physicians to remove unnecessary urinary catheters, beginning 3 days after insertion. Clinical, microbiological, pharmaceutical, and cost data were collected.Results.A total of 2,412 patients were enrolled in the study. No differences were found in the demographic and/or clinical characteristics of patients between the preintervention and postintervention periods. After the intervention, reductions were found in the rate of inappropriate urinary catheterization (mean rate, preintervention vs postintervention, 20.4% vs 11% [P = .04]), the rate of catheter-associated urinary tract infection (CA-UTI) (mean rate, 21.5 vs 5.2 infections per 1,000 catheter-days [P <.001]), the duration of urinary catheterization (mean, 11 vs 3 days [P < .001]), and the total length of hospitalization (mean, 16 vs 5 days [P < .001]). A linear relationship was seen between the monthly average duration of catheterization and the rate of CA-UTI (r = 0.89; P < .001). The intervention had the greatest impact on the rate of CA-UTI in the intensive care units (mean rate, preintervention vs postintervention, 23.4 vs 3.5 infections per 1,000 catheter-days [P = .01]). The monthly hospital costs for antibiotics to treat CA-UTI were reduced by 63% (mean, $3,739 vs $1,378 [P < .001]), and the hospitalization cost for each patient during the intervention was reduced by 58% (mean, $366 vs $154 [P < .001]).Conclusions.This study suggests that a multifaceted intervention to remind physicians to remove unnecessary urinary catheters can significantly reduced the duration of urinary catheterization and the CA-UTI rate in a hospital in a developing country.
Outbreak of Healthcare-Associated Infection and Colonization With Multidrug-ResistantSalmonella entericaSerovar Senftenberg in Florida
Authors: Kay Robyn S. , Vandevelde Alexander G. , Fiorella Paul D. , Crouse Rebecca , Blackmore Carina , Sanderson Roger , Bailey Christina L. , Sands Michael L. 
Published: June 2007

Background.In July 1999, a rare strain of multidrug-resistantSalmonella entericaserovar Senftenberg was isolated from the sputum of a trauma patient. Over a 6-year period (1999-2005) in northeast Florida, thisSalmonellaserovar spread to 66 other patients in 16 different healthcare facilities as a result of frequent transfers of patients among institutions. To our knowledge, this is the first outbreak of healthcare-associated infection and colonization with a fluoroquinolone-resistant strain of S. Senftenberg in the United States.Objectives.To investigate an outbreak of infection and colonization with an unusual strain of S. Senftenberg and assist with infection control measures.Design.A case series, outbreak investigation, and microbiological study of all samples positive forS.Senftenberg on culture.Setting.Cases ofS.Senftenberg infection and colonization occurred in hospitals and long-term care facilities in 2 counties in northeast Florida.Results.The affected patients were mostly elderly persons with multiple medical conditions. They were frequently transferred between healthcare facilities. ThisSalmonellaserovar was capable of long-term colonization of chronically ill patients. AllS.Senftenberg isolates tested shared a similar pulsed-field gel electrophoresis (PFGE) pattern.Conclusion.A prolonged outbreak of infection and colonization with multidrug-resistantS.Senftenberg was identified in several healthcare facilities throughout the Jacksonville, Florida, area and became established when infection control measures failed. The bacterial agent was capable of long-term colonization in chronically ill patients. Because the dispersal pattern of this strain suggested a breakdown of infection control practices, a multipronged intervention approach was undertaken that included intense education of personnel in the different institutions, interinstitutional cooperation, and transfer paperwork notification.
Underresourced Hospital Infection Control and Prevention Programs: Penny Wise, Pound Foolish?
Authors: Anderson Deverick J. , Kirkland Kathryn B. , Kaye Keith S. , Thacker Paul A. , Kanafani Zeina A. , Auten Grace , Sexton Daniel J. 
Published: June 2007

Objectives.To estimate the cost of healthcare-associated infections (HAIs) in a network of 28 community hospitals and to compare this sum to the amount budgeted for infection control programs at each institution and for the entire network.Design.We reviewed literature published since 1985 to estimate costs for specific HAIs. Using these estimates, we determined the costs attributable to specific HAIs in a network of 28 hospitals during a 1-year period (January 1 through December 31, 2004). Cost-saving models based on reductions in HAIs were calculated.Setting.Twenty-eight community hospitals in the southeastern region of the United States.Results.The weight-adjusted mean cost estimates for HAIs were $25,072 per episode of ventilator-associated pneumonia, $23,242 per nosocomial blood stream infection, $10,443 per surgical site infection, and $758 per catheter-associated urinary tract infection. The median annual cost of HAIs per hospital was $594,683 (interquartile range [IQR], $299,057-$l,287,499). The total annual cost of HAIs for the 28 hospitals was greater than $26 million. Hospitals budgeted a median of $129,000 (IQR, $92,500-$200,000) for infection control; the median annual cost of HAIs was 4.6 (IQR, 3.4-8.0) times the amount budgeted for infection control. An annual reduction in HAIs of 25% could save each hospital a median of $148,667 (IQR, $74,763-$296,861) and could save the group of hospitals more than $6.5 million.Conclusions.The economic cost of HAIs in our group of 28 study hospitals was enormous. In the modern age of infection control and patient safety, the cost-control ratio will become the key component of successful infection control programs.
213Bi‐radioimmunotherapy defeats early‐stage disseminated gastric cancer in nude mice
Authors: Beck Roswitha , Seidl Christof , Pfost Birgit , Morgenstern Alfred , Bruchertseifer Frank , Baum Hannsjörg , Schwaiger Markus , Senekowitsch‐Schmidtke Reingard 
Published: June 2007

The α‐emitter 213Bi is characterized by a high relative biological effectiveness. 213Bi‐immunoconjugates targeting tumor‐specific d9‐E‐cadherin have been proven to effectively kill tumor cells in a murine peritoneal carcinomatosis model. The aim of the present study was to optimize the efficacy of 213Bi‐radioimmunotherapy for disseminated gastric cancer in a mouse model of early‐ and advanced‐stage disease and to evaluate the long‐term toxicity of 213Bi‐immunoconjugates. For that purpose, nude mice were treated with different activities of 213Bi‐d9 monoclonal antibody (MAb) targeting d9‐E‐cadherin or unspecific 213Bi‐d8MAb at days 1 or 8 after inoculation of HSC45‐M2 gastric cancer cells expressing mutant d9‐E‐cadherin. Therapeutic efficacy was evaluated by monitoring survival for up to 300 days. Long‐term toxicity was evaluated by the survival of tumor‐free mice injected with 213Bi‐immunoconjugates, kidney function parameters and histopathological examination of kidneys. We showed that survival was significantly prolonged following treatment of mice with 213Bi‐immunoconjugates (0.37–22.2 MBq) at day 1 after tumor cell inoculation (P < 0.002). Therapy with 1.85 MBq of 213Bi‐d9MAb was most successful, defeating early‐stage disease in 87% of all cases. Treatment at day 8 after tumor cell inoculation was less efficient. Long‐term nephrotoxicity could only be observed following application of 22.2 MBq of 213Bi‐d9MAb, the highest activity applied in the therapy trials. As treatment with 1.85 MBq 213Bi‐d9MAb showed excellent therapeutic efficacy without any signs of acute or chronic toxicity, radioimmunotherapy with the α‐emitter 213Bi is a promising concept for treatment of early peritoneal carcinomatosis. (Cancer Sci 2007; 98: 1215–1222)
Management of cold haemolytic syndrome
Authors: Gertz Morie A. 
Published: June 2007

SummaryMost haemolytic disease is mediated by immunoglobulin G (IgG) antibodies and leads to red blood cell destruction outside of the circulatory system. However, rare syndromes, such as paroxysmal cold haemoglobinuria, show IgG antibodies causing intravascular destruction. Haemolysis may also occur because of immunoglobulin M antibodies. Historically, these antibodies have been termed ‘cold agglutinins’ because they cause agglutination of red blood cells at 3°C. Cold agglutinin haemolytic anaemia has been associated with a number of autoimmune and lymphoproliferative disorders, and its management differs substantially from warm antibody‐mediated haemolytic anaemia. This review of cold haemolytic syndromes describes new therapies and clinical strategies to determine a correct diagnosis.
Protein metabolism in Turner syndrome and the impact of hormone replacement therapy
Authors: Gravholt Claus Højbjerg , Riis Anne Lene , Møller Niels , Christiansen Jens Sandahl 
Published: June 2007

SummaryBackground  Studies have documented an altered body composition in Turner syndrome (TS). Body fat is increased and muscle mass is decreased. Ovarian failure necessitates substitution with female hormone replacement therapy (HRT), and HRT induces favourable changes in body composition. It is unknown how HRT affects protein metabolism.Aim  To test whether alterations in body composition before and after HRT in TS are a result of altered protein metabolism.Design  We performed a randomized crossover study with active treatment (HRT in TS and oral contraceptives in controls) or no treatment.Materials and methods  We studied eight women (age 29·7 ± 5·6 (mean ± SD) years) with TS, verified by karyotype, and eight age‐matched controls (age 27·3 ± 4·9 years). All subjects underwent a 3‐h study in the postabsorptive state. Protein dynamics of the whole body and of the forearm muscles were measured by an amino acid tracer dilution technique using [15N]phenylalanine and [2H4]tyrosine. Substrate metabolism was examined by indirect calorimetry.Results  Energy expenditure was comparable among TS and controls, and did not change during active treatment. Whole‐body phenylalanine and tyrosine fluxes were similar in the untreated situations, and did not change during active treatment. Amino acid degradation and protein synthesis were similar in all situations. Muscle protein breakdown was similar among groups, and was not affected by treatment. Muscle protein synthesis rate and forearm blood flow did not differ among groups or due to treatment.Conclusion  Protein metabolism in TS is comparable to controls, and is not affected by HRT.
Inherited lipodystrophies and the metabolic syndrome
Authors: Monajemi Houshang , Stroes Erik , Hegele Robert A. , Fliers Eric 
Published: June 2007

SummaryLipodystrophies represent a heterogeneous group of diseases characterized by an abnormal subcutaneous fat distribution, the extent of which can vary from localized, to partial, to generalized lipoatrophy. Whereas partial and generalized lipodystrophies are each associated with metabolic abnormalities, the localized form is not. These metabolic changes include insulin resistance with type 2 diabetes, acanthosis nigricans, dyslipidaemia predominantly consisting of hypertriglyceridaemia (associated with the onset of pancreatitis) and depressed HDL cholesterol, liver steatosis and hypertension. Affected women are often hirsute and this can be associated with the presence of polycystic ovarian syndrome (PCOS). Most of these clinical features are present to some extent in patients with the common metabolic syndrome. As the prevalence of metabolic syndrome far outweighs that of lipodystrophy, the diagnosis of this rare disorder may often be overlooked with the affected patient diagnosed as merely being ‘yet’ another case of metabolic syndrome. In this article, we draw attention to the importance of recognizing patients with lipodystrophy who present with metabolic abnormalities, as both the diagnostic as well as the therapeutic approach of these patients differ profoundly from patients with the metabolic syndrome.