bluuebunny/crossref_metadata_2025_split huggingface dataset:
Uteroplacental insufficiency down regulates insulin receptor and affects expression of key enzymes of long-chain fatty acid (LCFA) metabolism in skeletal muscle at birth
Authors: Germani Daniela , Puglianiello Antonella , Cianfarani Stefano 
Published: May 2008

Abstract

Background
Epidemiological studies have revealed a relationship between early growth restriction and the subsequent development of insulin resistance and type 2 diabetes. Ligation of the uterine arteries in rats mimics uteroplacental insufficiency and serves as a model of intrauterine growth restriction (IUGR) and subsequent developmental programming of impaired glucose tolerance, hyperinsulinemia and adiposity in the offspring. The objective of this study was to investigate the effects of uterine artery ligation on the skeletal muscle expression of insulin receptor and key enzymes of LCFA metabolism.

Methods
Bilateral uterine artery ligation was performed on day 19 of gestation in Sprague-Dawley pregnant rats. Muscle of the posterior limb was dissected at birth and processed by real-time RT-PCR to analyze the expression of insulin receptor, ACCα, ACCβ (acetyl-CoA carboxylase alpha and beta subunits), ACS (acyl-CoA synthase), AMPK (AMP-activated protein kinase, alpha2 catalytic subunit), CPT1B (carnitine palmitoyltransferase-1 beta subunit), MCD (malonyl-CoA decarboxylase) in 14 sham and 8 IUGR pups.
Muscle tissue was treated with lysis buffer and Western immunoblotting was performed to assay the protein content of insulin receptor and ACC.

Results
A significant down regulation of insulin receptor protein (p < 0.05) and reduced expression of ACS and ACCα mRNA (p < 0.05) were observed in skeletal muscle of IUGR newborns. Immunoblotting showed no significant change in ACCα content.

Conclusion
Our data suggest that uteroplacental insufficiency may affect skeletal muscle metabolism down regulating insulin receptor and reducing the expression of key enzymes involved in LCFA formation and oxidation.
The microneme proteins CTRP and SOAP are not essential for Plasmodium berghei ookinete to oocyst transformation in vitro in a cell free system
Authors: Nacer Adéla , Underhill Ann , Hurd Hilary 
Published: May 2008

Abstract

Background
Two Plasmodium berghei ookinete micronemal proteins, circumsporozoite and TRAP related protein (CTRP) and secreted ookinete adhesive protein (SOAP) both interact with the basal lamina component laminin. Following gene disruption studies it has been proposed that, apart from their role in motility, these proteins may be required for interactions leading to ookinete-to-oocyst transformation.

Methods
CTRP and SOAP null mutant P. berghei ookinetes were compared to P. berghei ANKA wild-type for their ability to transform and grow in vitro. To confirm in vitro findings for P. berghei CTRP-KO ookinetes were injected into the haemocoel of An opheles gambiae female mosquitoes.

Results
Transformation, growth, and viability were comparable for the gene disrupted and wild-type parasites. P. berghei CTRP-KO ookinetes were able to transform into oocysts in the haemocoel of An. gambiae mosquitoes.

Conclusion
Neither CTRP nor SOAP is required for parasite transformation in vitro. By-passing the midgut lumen allows for the transformation of P. berghei CTRP-KO ookinetes suggesting that it is not required for transformation in vivo.
Review of Australian health economic evaluation – 245 interventions: what can we say about cost effectiveness?
Authors: Dalziel Kim , Segal Leonie , Mortimer Duncan 
Published: May 2008

Abstract

Background
There is an increasing body of published cost-utility analyses of health interventions which we sought to draw together to inform research and policy.

Methods
To achieve consistency in costing base and policy context, study scope was limited to Australian-based cost-effectiveness analyses. Through a comprehensive literature review we identified 245 health care interventions that met our study criteria.

Results
The median cost-effectiveness ratio was A$18,100 (~US$13,000) per QALY/DALY/LY (quality adjusted life year gained or, disability adjusted life year averted or life year gained). Some modalities tended to perform worse, such as vaccinations and diagnostics (median cost/QALY $58,000 and $68,000 respectively), than others such as allied health, lifestyle, in-patient interventions (median cost/QALY/DALY/LY all at ~A$9,000~US$6,500). Interventions addressing some diseases such as diabetes and impaired glucose tolerance or alcohol and drug dependence tended to perform well (median cost/QALY/DALY/LY < A$3,700, < US$5,000). Interventions targeting younger persons < 25 years (median cost/QALY/DALY/LY < A$41,200) tended to perform less well than those targeting adults > 25 years (median cost/QALY/DALY/LY < A$16,000). However, there was also substantial variation in the cost effectiveness of individual interventions within and across all categories.

Conclusion
For any given condition, modality or setting there are likely to be examples of interventions that are cost effective and cost ineffective. It will be important for decision makers to make decisions based on the individual merits of an intervention rather than rely on broad generalisations. Further evaluation is warranted to address gaps in the literature and to ensure that evaluations are performed in areas with greatest potential benefit.
Persistent Borna Disease Virus (BDV) infection activates microglia prior to a detectable loss of granule cells in the hippocampus
Authors: Ovanesov Mikhail V , Moldovan Krisztina , Smith Kimberly , Vogel Michael W , Pletnikov Mikhail V 
Published: May 2008

Abstract
Neonatal Borna Disease Virus (BDV) infection in rats leads to a neuronal loss in the cortex, hippocampus and cerebellum. Since BDV is a non-lytic infection in vitro, it has been suggested that activated microglia could contribute to neuronal damage. It is also conceivable that BDV-induced cell death triggers activation of microglia to remove cell debris. Although an overall temporal association between neuronal loss and microgliosis has been demonstrated in BDV-infected rats, it remains unclear if microgliosis precedes or results from neuronal damage. We investigated the timing of microglia activation and neuronal elimination in the dentate gyrus (DG) of the hippocampus. We found a significant increase in the number of ED1+ microglia cells as early as 10 days post infection (dpi) while a detectable loss of granule cells of the DG was not seen until 30 dpi. The data demonstrate for the first time that a non-lytic persistent virus infection of neurons activates microglia long before any measurable neuronal loss.
Neuroinflammatory response to lipopolysaccharide is exacerbated in mice genetically deficient in cyclooxygenase-2
Authors: Aid Saba , Langenbach Robert , Bosetti Francesca 
Published: May 2008

Abstract

Background
Cyclooxygenases (COX) -1 and -2 are key mediators of the inflammatory response in the central nervous system. Since COX-2 is inducible by inflammatory stimuli, it has been traditionally considered as the most appropriate target for anti-inflammatory drugs. However, the specific roles of COX-1 and COX-2 in modulating a neuroinflammatory response are unclear. Recently, we demonstrated that COX-1 deficient mice show decreased neuroinflammatory response and neuronal damage in response to lipopolysaccharide (LPS).

Methods
In this study, we investigated the role of COX-2 in the neuroinflammatory response to intracerebroventricular-injected LPS (5 μg), a model of direct activation of innate immunity, using COX-2 deficient (COX-2-/-) and wild type (COX-2+/+) mice, as well as COX-2+/+ mice pretreated for 6 weeks with celecoxib, a COX-2 selective inhibitor.

Results
Twenty-four hours after LPS injection, COX-2-/- mice showed increased neuronal damage, glial cell activation, mRNA and protein expression of markers of inflammation and oxidative stress, such as cytokines, chemokines, iNOS and NADPH oxidase. Brain protein levels of IL-1β, NADPH oxidase subunit p67phox, and phosphorylated-signal transducer and activator of transcription 3 (STAT3) were higher in COX-2-/- and in celecoxib-treated mice, compared to COX-2+/+ mice. The increased neuroinflammatory response in COX-2-/- mice was likely mediated by the upregulation of STAT3 and suppressor of cytokine signaling 3 (SOCS3).

Conclusion
These results show that inhibiting COX-2 activity can exacerbate the inflammatory response to LPS, possibly by increasing glial cells activation and upregulating the STAT3 and SOCS3 pathways in the brain.
The inhibition of the Human Immunodeficiency Virus type 1 activity by crude and purified human pregnancy plug mucus and mucins in an inhibition assay
Authors: Habte Habtom H , de Beer Corena , Lotz Zoë E , Tyler Marilyn G , Schoeman Leann , Kahn Delawir , Mall Anwar S 
Published: May 2008

Abstract

Background
The female reproductive tract is amongst the main routes for Human Immunodeficiency Virus (HIV) transmission. Cervical mucus however is known to protect the female reproductive tract from bacterial invasion and fluid loss and regulates and facilitates sperm transport to the upper reproductive tract. The purpose of this study was to purify and characterize pregnancy plug mucins and determine their anti-HIV-1 activity in an HIV inhibition assay.

Methods
Pregnancy plug mucins were purified by caesium chloride density-gradient ultra-centrifugation and characterized by Western blotting analysis. The anti-HIV-1 activities of the crude pregnancy plug mucus and purified pregnancy plug mucins was determined by incubating them with HIV-1 prior to infection of the human T lymphoblastoid cell line (CEM SS cells).

Results
The pregnancy plug mucus had MUC1, MUC2, MUC5AC and MUC5B. The HIV inhibition assay revealed that while the purified pregnancy plug mucins inhibit HIV-1 activity by approximately 97.5%, the crude pregnancy plug mucus failed to inhibit HIV-1 activity.

Conclusion
Although it is not clear why the crude sample did not inhibit HIV-1 activity, it may be that the amount of mucins in the crude pregnancy plug mucus (which contains water, mucins, lipids, nucleic acids, lactoferrin, lysozyme, immunoglobulins and ions), is insufficient to cause viral inhibition or aggregation.
Calcific myofibrosis due to pentazocine abuse: a case report
Authors: Goyal Vinay , Chawla Jatinder M , Balhara Yatan P S , Shukla Garima , Singh Sumit , Behari Madhuri 
Published: May 2008

Abstract

Introduction
Pentazocine, a synthetic narcotic analgesic, is commonly used for the relief of moderate to severe pain secondary to various conditions. It is usually well tolerated; however, adverse effects are not uncommon, especially when higher doses are used and when it is used in a dependent fashion. There have been reports of various complications associated with its use, including skin fibrosis, skin ulceration, abnormal skin pigmentation and symmetrical myopathy with fibrous myopathy. Fibrosis has usually been reported in the muscles at the site of injection of the drug. Being opioid in nature, it has a high abuse potential.

Case presentation
Here we report a case of pentazocine-induced calcific myofibrosis in a 42-year-old man involving muscles which were not injected with pentazocine.

Conclusion
This case highlights the care that needs to be taken when prescribing opioid analgesics, such as pentazocine, as routine painkillers. Patients who have history of substance abuse are more likely to abuse other agents, including prescription drugs. Rare consequences such as calcific myofibrosis are devastating and can cause significant lifelong disability.
Combined effects of 5-Fluorouracil, Folinic acid and Oxaliplatin on the expression of carcinoembryonic antigen in human colon cancer cells: pharmacological basis to develop an active antitumor immunochemotherapy
Authors: Prete Salvatore P , Turriziani Mario , Massara Maria C , De Rossi Alessia , Correale Pierpaolo , De Vecchis Liana , Torino Francesco , Bonmassar Laura , Aquino Angelo 
Published: May 2008

AbstractBackgroundFive-fluorouracil (FU), mainly associated with leucovorin (L), plays an essential role in chemotherapy of colorectal carcinoma. Moreover, FU ± L has been found to increase the expression of tumor-associated carcinoembryonic antigen (CEA), that may be an important target in therapeutic protocols of active specific immunotherapy. FU + L (FUL) are frequently combined with oxaliplatin (OXA) in advanced colon cancer patients. Thus, we investigated whether FUL in combination with OXA according to 2 different schedules may influence CEA expression in human colon cancer cells in vitro.MethodsCEA protein expression was evaluated by cytofluorimetric and western blot analysis. Relative quantification of CEA mRNA was assessed by real time RT-PCR analysis.ResultsLevels of CEA protein and transcript were found to be higher in FUL-treated cells than in controls. However, when target cells were exposed to OXA before but not after FUL treatment, the up-regulation of CEA was partially inhibited.ConclusionThese results suggest that target cells must be exposed to OXA after but not before treatment with the fluoropyrimidine in order to exploit drug-induced up-regulation of CEA. This finding appears to provide useful information to design chemo-immunotherapy protocols based on FUL + OXA, combined with host's immunity against CEA directed cancer vaccines.
Phase I Dose Escalation and Pharmacokinetic Study of Lapatinib in Combination With Trastuzumab in Patients With Advanced ErbB2-Positive Breast Cancer
Authors: Storniolo Anna Maria , Pegram Mark D. , Overmoyer Beth , Silverman Paula , Peacock Nancy W. , Jones Suzanne F. , Loftiss Jill , Arya Nikita , Koch Kevin M. , Paul Elaine , Pandite Lini , Fleming Ronald A. , Lebowitz Peter F. , Ho Peter T.C. , Burris Howard A. 
Published: May 2008

Purpose The combination of lapatinib and trastuzumab has been observed to have a synergistic, antiproliferative effect against ErbB2-positive breast cancer cells in vitro. This phase I study assessed the safety, clinical feasibility, optimally tolerated regimen (OTR), pharmacokinetics (PK), and preliminary clinical activity of this combination in patients with ErbB2-positive advanced breast cancer. Patients and Methods Cohorts of three patients with ErbB2-positive advanced breast cancer were treated with escalating doses of lapatinib (750 to 1,500 mg) administered once daily (continuous) in combination with trastuzumab (4 mg/kg loading dose then 2 mg/kg weekly) to determine the OTR. Once the OTR was determined, additional patients were enrolled to provide the PK profile of both agents alone and in combination. Results A total of 54 patients were treated: 27 in the dose-escalation group and 27 in the PK group. Overall, adverse events were mild to moderate in severity, with no drug-related grade 4 events. The most frequent drug-related grade 3 events included diarrhea (17%), fatigue (11%), and rash (6%). The OTR was 1,000 mg lapatinib with standard weekly trastuzumab. One patient had a complete response and seven patients had partial responses. The PK parameters (maximum concentration in plasma and area under the curve) of lapatinib and trastuzumab in combination were not significantly different than when either was administered alone. Conclusion The OTR of the lapatinib/trastuzumab combination was lapatinib 1,000 mg per day with standard weekly trastuzumab. At these doses, the regimen was well tolerated and clinically active in this heavily pretreated ErbB2-positive breast cancer population.
Measuring Carbohydrate-Deficient Transferrin by Direct Immunoassay: Factors Affecting Diagnostic Sensitivity for Excessive Alcohol Intake
Authors: Whitfield John B , Dy Veronica , Madden Pamela A F , Heath Andrew C , Martin Nicholas G , Montgomery Grant W 
Published: May 2008

AbstractBackground: Carbohydrate-deficient transferrin (CDT) is a marker of alcohol intake that is used for detecting or monitoring alcohol-use disorders. The introduction of a new direct immunoassay for CDT justifies reevaluation of test performance and reexamination of factors affecting test diagnostic sensitivity and specificity.Methods: Individuals enrolled in twin/family studies of alcohol use and dependence provided blood samples and information on recent alcohol use. Serum CDT concentration was measured in 2 088 people with the N Latex CDT (Dade Behring) method, and CDT percentage (CDT%) was calculated as the proportion of the total transferrin concentration measured with Roche reagents.Results: Diagnostic sensitivity was low, both for comparisons of men who reported an alcohol intake of &gt;28 drinks/week vs those who consumed ≤28 drinks/week (28% sensitivity) and for women who consumed &gt;14 drinks/week vs those who consumed ≤14 drinks/week (18% sensitivity), at cutoff values that yielded a 95% specificity. Body mass index, variables associated with metabolic syndrome, and smoking had notable effects on the probability of an abnormal CDT result with excessive alcohol use. Diagnostic sensitivity was greater in men of normal weight (43%) than in obese men (10%) and greater in male smokers (38%) than in male nonsmokers (21%). In women, diagnostic sensitivities were ≤20%, even for those of normal weight and for smokers.Conclusions: CDT is a poor marker of excessive alcohol intake in both women and men who are overweight or obese. It is also less useful in nonsmokers than in smokers. The diagnostic performance of the direct immunoassay and the effects of obesity and smoking are similar to those reported with previous anion-exchange immunoassay methods.
Sublingual Immunotherapy: A Novel, Albeit Not so New, Immunotherapy Treatment Modality
Authors: Saporta Diego 
Published: May 2008

Background Specific allergy immunotherapy traditionally has been thought of as subcutaneous injection immunotherapy (SCIT). There also are noninjection routes for the administration of immunotherapy. The best-known and studied of these noninjection routes is the sublingual route, usually known as sublingual immunotherapy (SLIT). SLIT has been in use for many decades; however, to this date, it is not well known to the majority of allergy practitioners in this country. The purpose of this study is to help change this perception so that SLIT eventually can be considered one more tool in the allergist's armamentarium. Methods A literature review was performed. It included articles from the early American clinicians and present publications that are mostly of European origin. Results It will become clear to the reader that the key features of SLIT are its efficacy, great safety, and simplicity of administration. Conclusion SLIT is a safe treatment modality that should be considered as a useful additional tool in the therapeutic armamentarium.
Effect of Ginkgo Biloba and Dexamethasone in the Treatment of 3-methylindole-induced Anosmia Mouse Model
Authors: Lee Chul Hee , Mo Ji-Hun , Shim Seung Hee , Ahn Jung-Min , Kim Jeong-Whun 
Published: May 2008

Background Olfactory loss is a challenging disease. Although glucocorticoid is sometimes used for the treatment of anosmia, it has been reported that it potentiated neural damage in the early phase of treatment. This study is designed to identify the effect of ginkgo biloba, an antioxidant that acts as a free radical scavenger, in the treatment of olfactory injury aggravated by dexamethasone. Methods Anosmia mouse model was induced by i.p. injection of 3-methylindole (3-MI). Twenty-five mice were divided into one control group without anosmia and four anosmia treatment groups (given treatments of dexamethasone and/or ginkgo biloba). The effects of treatment were evaluated by behavioral test, Western blot, and immunohistochemistry 2 weeks after 3-MI injection. Results Induction of anosmia was confirmed by behavioral tests. The thickness and cell number of olfactory neuroepithelium were decreased more significantly in the dexamethasone treatment group than in the combination treatment group. The expression of olfactory marker protein (OMP) in olfactory epithelium was more decreased also in the dexamethasone treatment group than in the combination treatment group. The expression of OMP was decreased significantly in the olfactory bulbs of anosmia groups but there were no differences between the anosmia treatment groups. Conclusion Dexamethasone treatment was associated with further deterioration of olfactory injury by 3-MI and it was recovered by combination treatment of dexamethasone and ginkgo biloba. The antioxidant effect of ginkgo biloba might play a role in restoration of olfactory loss and it was effective only when oxidative stress is maximized by dexamethasone.
Prevalence of Biofilm-forming Bacteria in Chronic Rhinosinusitis
Authors: Prince Anthony A. , Steiger Jacob D. , Khalid Ayesha N. , Dogrhamji Laurel , Reger Christine , Claire Steven Eau , Chiu Alexander G. , Kennedy David W. , Palmer James N. , Cohen Noam A. 
Published: May 2008

Background Recently, biofilms have been implicated in the pathogenesis of recalcitrant chronic rhinosinusitis (CRS). We sought to determine the prevalence of biofilm-forming cultures obtained from patients with CRS and clinical factors that may contribute to biofilm formation. Methods Endoscopically guided sinonasal cultures were obtained in duplicate from CRS patients with evidence of mucopurulence. Bacterial swabs were sent for microbiological characterization and were simultaneously evaluated for biofilm-forming capacity by a modified Calgary Biofilm Detection Assay. Biofilm formation was based on concomitant values of biofilm-forming Pseudomonas aeruginosa O1 (PAO1) (positive control) and non-biofilm-forming mutants sad-31 (type IV pili) and sad-36 (flagella K; negative control). Samples, with growth greater than the sad-31 mutant, were designated as biofilm formers. Results Sinonasal cultures were obtained from 157 consecutive patients (83 female patients) over a 4-month period. Forty-five samples (28.6%) showed biofilm formation. Among patients with a prior history of functional endoscopic sinus surgery (FESS), 30.7% (n = 42) showed biofilm growth. For patients naive to surgical intervention (n = 20), only 15% showed biofilm formation. A positive, statistically significant correlation existed between biofilm formation and number of prior FESS procedures. Polymicrobial cultures, Pseudomonas aeruginosa, and/or Staphylococcus aureus comprised 71% of samples. Chi-squared analysis showed an association with prior infections, but not with any pharmacologic therapy or comorbidies. Conclusion We show a high percentage of CRS patients (28.6%) whose sinonasal mucopurulence has biofilm-forming capacity. Postsurgical patients had a high prevalence of biofilm-forming bacteria, a possible reflection of the severe nature of their disease. Additional studies are warranted.
Forecasting commodity prices: GARCH, jumps, and mean reversion
Authors: Bernard Jean‐Thomas , Khalaf Lynda , Kichian Maral , Mcmahon Sebastien 
Published: May 2008

AbstractIn examining stochastic models for commodity prices, central questions often revolve around time‐varying trend, stochastic convenience yield and volatility, and mean reversion. This paper seeks to assess and compare alternative approaches to modelling these effects, with focus on forecast performance. Three specifications are considered: (i) random‐walk models with GARCH and normal or Student‐t innovations; (ii) Poisson‐based jump‐diffusion models with GARCH and normal or Student‐t innovations; and (iii) mean‐reverting models that allow for uncertainty in equilibrium price. Our empirical application makes use of aluminium spot and futures price series at daily and weekly frequencies. Results show: (i) models with stochastic convenience yield outperform all other competing models, and for all forecast horizons; (ii) the use of futures prices does not always yield lower forecast error values compared to the use of spot prices; and (iii) within the class of (G)ARCH random‐walk models, no model uniformly dominates the other. Copyright © 2008 John Wiley & Sons, Ltd.