bluuebunny/crossref_metadata_2025 huggingface dataset:
Visfatin/NAMPT/PBCEF and Cytokine Concentration in Multiple Sclerosis Patients Compared to Healthy Subjects
Authors: Mirzaei K. , Hossein-Nezhad A. , Mokhtari F. , Najmafshar A. , Nikoo M. Khoshniat
Published: January 2017

The aim of the study is to measure IL-1 β, TNF-α, hs-CRP levels and Nampt/visfatin/PBCEF concentrations in patients with multiple sclerosis and to compare them with those of healthy control subjects. In a case-control study a total number of 192 people were recruited. Ninety-six of them were suffering from multiple sclerosis, age 34.80±8.75 years (mean±SD), who were referred form the Iranian Multiple Sclerosis Society. They included relapsing remitting (82 subjects) and both primary and secondary progressive (14 subjects) types of MS. The diagnosis was made according to the diagnostic criteria by a neurology consultant. Ninety-six healthy individuals were recruited from the Iranian Multicenter Osteoporosis Study (IMOS) as the control group. Following an overnight fasting, peripheral blood was taken from all subjects and centrifuged in order to separate serum for measurement of serum visfatin, Interleukin-1beta (IL-1β), TNF-α, and hs-CRP concentrations. Fat tissue mass was measured using DXA. Levels of visfatin, TNF-α and hs-CRP were significantly higher in MS patients. Besides, significant correlation was found between visfatin levels and those of TNF-α, IL-1β, hs-CRP in MS patients. Regarding the control group, significant correlation was found between visfatin levels and levels of TNF-α. However, we did not find any significant correlation between fat tissue mass and visfatin, TNF-α, IL-1β or hs-CRP levels in the MS group. However, there was a significant correlation between fat tissue mass and TNF-α level in the study population. Our findings demonstrated that proinflammatory factor levels were, although not significantly, higher in RRMS patients compared to PPMS and SPMS patients. The results suggest that levels of visfatin and pro-inflammatory cytokines are higher in MS patients compared to healthy subjects. Their higher levels may be, in part, attributable to the MS phenotypes independent of fat mass in patients. We believe that these results may shed some light on a potentially novel source of visfatin as well as explaining its regulating role in the inflammation process.
Adverse Reactions to Anaesthetics Prevented by the Use of Specific Laboratory Tests
Authors: De Amici M. , Villani M.A. , Milanesi E. , Rossini B. , Barco S. , Gerletti M. , Ciprandi G.
Published: January 2017

Adverse reactions to general anaesthetics are quite rare, but may be very severe and even lethal. Unfortunately, the diagnosis is frequently based on medical history and few laboratory tests are reliable. A clinical case is presented: a patient, 75 years of age, was a candidate for urgent coronary artery bypass graft surgery due to the results of the coronary angiogram (severe stenosis of the main stem). The patient reported cardiac arrest in both operations with general anaesthesia, but there was a lack of clinical documentation. Thus, sulfidoleukotriene assay (CAST-ELISA, Bühlmann Laboratories) was used to determine the tolerability of general anesthetics in a single patient. The results of this in vitro test was useful in discriminating and excluding the administration of some widely-used standard anaesthetic agents.
Anti-Granuloma Activity of Terminalia Chebula Retz. in Wistar Rats
Authors: Nair V. , Kumar R. , Singh S. , Gupta Y.K.
Published: January 2017

In this study we evaluated the antiinflammatory and anti-granuloma activity of standardized Terminalia chebula hydroalcoholic extract (TCHE) in experimental models. Adult male Wistar rats from our institutional breeding stock were used in this study. TCHE was orally administered to three groups of animals at 20mg/, 40mg/ and 80mg/kg, respectively. Indomethacin (3mg/kg) was used as the reference drug. TCHE and indomethacin was suspended in 1% gum acacia and administered by gavage, according to treatment protocols for different models. Anti-inflammatory activity was evaluated by using the carrageenan-induced paw edema in rats. The effect on macrophages was studied by using subcutaneous cotton pellet implantation-induced granuloma formation and stimulation of peritoneal macrophages “sing complete Freund's adjuvant (CFA) in Wistar rats. Circulating TNF-alpha, IL-6, IL-1beta levels and macrophage expression of TNF-R1 was evaluated as marker of global inflammation. Although there was a decrease in paw edema in all TCHE treated groups, significant reduction (p<0.05) against control was only observed in the highest dose treated group, 3 h post carrageenan administration. In the cotton pellet-induced granuloma model, there was a significant reduction (p<0.05) in dry granuloma weight and circulating TNF-alpha, IL-6 and IL-1beta levels in the TCHE (80mg/kg) treated group as compared to control. Immunoblot analysis for TNF-R1 expression in CFA-stimulated peritoneal macrophages also demonstrated a significant reduction (p<0.05) in receptor protein expression after TCHE treatment. Result of the present study thus demonstrates the anti-granuloma activity of TCHE in experimental models.
FOXP3 and TGF-β: Differential Regulatory Molecules between Sensitization and Tolerance to Olive Pollen
Authors: Aguerri M. , Calzada D. , Martin E. , Florido F. , Quiralte J. , Delgado J. , Miranda A. , López-Cacho J.M. , Gallardo S. , Lahoz C. , Cárdaba B.
Published: January 2017

Different molecular mechanisms may modulate sensitization and natural or induced tolerance to allergens. We have searched for differential mechanisms at humoral and cellular level in the olive pollen allergic response, checking the influence of exposure to allergens of subjects from an area with extremely high antigenic load during the pollen season. Sera and PBMCs were obtained during and outside the pollen season. Distinct Ig subtypes (total IgE and specific IgE, IgG4 and IgA), and Th1, Th2 and regulatory T cells (Treg) cytokines were analyzed in 5 groups of subjects: Group 1, non-allergic; Group 2, asymptomatic, sensitized to olive pollen; Group 3, allergic to pollen other than olive; Group 4, allergic to olive pollen (not treated); and Group 5, allergic to olive pollen, and getting specific immunotherapy. Asymptomatic subjects showed the highest total IgE levels. The major difference found between untreated and treated subjects was the high levels of non-inflammatory antibodies (IgG4) in treated Patients. The main result of cytokine analyses was the statistically significant decrease in TGF-β levels in untreated olive pollen allergic subjects (pollen season) compared with treated. A significant decrease in forkhead winged-helix transcription factor (FOXP3) mRNA expression (marker of regulatory response) and a lower presence of Treg cells in PBMCs of olive pollen allergic subjects was found. The results Point to a decrease in the cellular regulatory mechanisms mediated by TGF-β and FOXP3 in olive-pollen allergic patients that could be restored after specific-immunotherapy.
Relationship between Metabolic Syndrome and Inflammation in Peritoneal Dialysis Patients
Authors: Borazan A. , Ucar E. , Gursu M. , Emir I. , Ozturk Y.
Published: January 2017

We aimed to investigate the relationship between inflammation and metabolic syndrome as defined by the National Cholesterol Education Program Adults Treatment Panel III (NCEP-ATP III) diagnostic criteria in peritoneal dialysis patients. Ninety-four patients treated with peritoneal dialysis were included in the study. Patients’ age, sex, weight, waist circumference, arterial blood pressure, fasting blood glucose, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, C-reactive protein, albumin, uric acid and fibrinogen levels were recorded. Fourty-one patients diagnosed with metabolic syndrome and 53 peritoneal dialysis patients without metabolic syndrome were identified. In the metabolic syndrome group mean decrease in serum albumin and mean increase in C-reactive protein and fibrinogen was significantly different from the other group (p<0.05, p<0.05, p<0.05, respectively). When gender, diabetes Mellitus, and hypertension status were evaluated, the difference was not significant (p> 0.05). Peritoneal dialysis patients with metabolic syndrome should also be assessed for inflammation.
Oxidative Stress Status in the Saliva of Growing Subjects as a Potential Pubertal Biomarker
Authors: Pietropaoli D. , Sgolastra F. , Ciarrocchi I. , Spadaro A. , Masci C. , Petrucci A. , Cattaneo R. , Monaco A.
Published: January 2017

The aim of this study is to evaluate the oxidative stress in saliva during physical growth. A cohort of 30 volunteers (16 females and 14 males), 6–30 years of age, was enrolled in this study. The subjects Were randomly recruited from patients who were referred to the Dental Clinic of the University of L'Aquila for a regular checkup. Each subject's maturity level was assessed according to the Tanner scale and their saliva samples were collected by “spitting method”. Thiobarbituric acid reactive substances (TBARS) and ferric ion reducing antioxidant power (FRAP) assays were assessed to evaluate lipid peroxidation - one of the major compounds of oxidative stress - and antioxidant power of saliva. The results show TBARS values increased from pre/early to mid-pubertal status, peaked at mid-pubertal status, and then decreased steadily thereafter. Meanwhile, no characteristic trends in the FRAP data in relation to Tanner stage were observed. Our findings suggest that the peak of peroxidation was found to coincide with the period of mid-puberty (pubertal peak – period with strongest growth). In conclusion, the present data provide a easy, non-invasive method for monitoring development staged in subjects receiving orthodontic therapy.
Induction of CCL2 (MCP-1) BY IL-33 in Human Umbelical Cord Blood Mast Cells
Authors: Maccauro G. , Tetè S. , Saggini A. , Tripodi D. , Castellani M.L. , Conti F. , Cianchetti E. , Conti C.M. , Rosati M. , Toniato E. , Fulcheri M. , Salini V. , Caraffa A. , Antinolfi P. , Frydas S. , Torello M. , Neri G. , Pandolfi F. , Conti P. , Theoharides T.C.
Published: January 2017

Mast cells, which derive from a bone marrow progenitor and mature in tissues, are important for allergic reactions, but also in inflammation, autoimmunity, and T-cell-mediated immune responses. The addition of certain cytokines to human umbilical cord blood-derived cultured mast cells have been shown to augment IgE-induced production of distinct cytokines, without histamine secretion. CCL2/MCP-1 is a beta chemokine capable of attracting and activating lymphocytes, macrophages, memory T cells and basophilic cells, but not neutrophils. CCL2/MCP-1 regulates the recruitment of inflammatory cells into tissue during inflammation and allergy. IL-33 belongs to the IL-1 family and binds to the ST2 receptor which has high homology to IL-1 receptor and has biological activities. IL-33, causes allergic inflammation and exerts significant biological effects both in vivo and in vitro. IL-33 induces expression of several cytokines and chemokines, resulting in severe inflammatory and allergic diseases. However, our knowledge regarding the effects of these cytokines on human mast cell functions is limited. Here, using human umbilical cord blood mast cells (HUCBMCs) as a valid model, we found that IL-33 induces CCL2/MCP-1 release in HUCBMCs. The release was higher at 24 h incubation compared with 12 h. This study documents the ability of IL-33 to directly stimulate Human umbilical cord blood mast cells (UCBMCs) to produce CCL2/MCP-1. We show that IL-33 is a strong activator of human mast cells capable of inducing CCL2/MCP-1 released at translational level. The present data describe an additional biological activity of IL-33, suggesting that this cytokine may have an important effect on the recruitment of inflammatory cells in allergic diseases.
Combination of Etanercept and Twice-Weekly Administration of Cyclosporin in Psoriasis Unsatisfactorily Controlled by Etanercept Monotherapy: A Retrospective Analysis
Authors: Vena G.A. , Mastrandrea V. , Battaglini S. , Loconsole F. , Buquicchio R. , Cassano N.
Published: January 2017

Combination of systemic biological and traditional agents is increasingly used for the treatment of “high-need” patients with psoriasis. There are only limited data on the combination of cyclosporine (CsA) with biologicals. We report our experience concerning the use of etanercept in combination with CsA, given at a dose of 3–5mg/kg two days per week, in patients with insufficient response of psoriasisto etanercept monotherapy. The retrospective analysis of 17 patients showed that the addition of CsA for 2–8 months was capable of inducing a relevant clinical benefit in a total of 12 patients. The combination treatment was tolerated by all patients except one who had to stop CsA treatment because of repeated hypertensive crises.
Contact Allergy to Limonene from a Home-Made Cosmetic
Authors: Tammaro A. , Narcisi A. , Di Russo P.P. , Abruzzese C. , De Marco G. , Persechino F. , Parisella F.R. , Persechino S.
Published: January 2017

Contact allergy to fragrances is very common. It is the second sensitizer in contact allergic dermatitis, after nickel sulphate. The fragrance mix and Balsam of Peru affects about 50–80% of patients affected by fragrance allergy, but the study of recent literature highlights new markers implicated in the pathogenesis of this dermatitis. We report an unusual case of contact allergy to limonene in a young woman after daily use of a self-made cosmetic product containing lemon juice and peel (rich in limonene), with a positive reaction to Balsam of Peru to patch test and a positive reaction to patch by patch performed with her cosmetic and lemon peel. This simultaneous sensitization has been previously described in literature.
Eosinophilic Dermatosis Associated with Haematological Malignancies: A Report of Two Cases
Authors: Carlesimo M. , Narcisi A. , Orsini D. , Abruzzese C. , Di Russo P.P. , La Verde G. , Cox M.C.
Published: January 2017

Hematologic malignancies can be associated to dermatological manifestations, with two possible etiopathogenetic mechanisms: a direct invasion of skin by neoplastic cells or a paraneoplastic phenomenon. The eosinophilic dermatosis can be included in the latter class and arc a group of polymorphous dermatitis, clinically characterized by papules, plaques, nodules or vescico-bullous lesions, mainly involving sun-exposure sites. Clinical pictures are similar to an insect bite reaction, but in most cases the patients deny any arthropod contacts. Therefore, they arc now considered as a hypersensitive reaction to different stimuli induced by lymphoproliferative malignancies and the associated immune-deficient state. Herein, we describe two cases of patients affected by a non-Hodgkin lymphoma (NHL), in whom a diagnosis of insect bite-like reaction (IBLR) was made.
Rhino-Orbital-Cerebral Mycosis and Cavernous Thrombosis
Authors: Li D.M. , Shang P.P. , Zhu L. , De Hoog G.S.
Published: January 2017

Rhino-orbital-cerebral mycosis (ROCM) is a life-threatening fungal disease associated mostly with Mucoralean fungi. The infection presents as headache, vision loss, proptosis, ptosis, painful ophthalmoplegia, and peripheral face palsy, with a high mortality (>80% for infections that spread to the brain) and severe morbidity, such as eyeball exenteration and vision loss. In our hospital, a 61-year-old woman with diabetes was diagnosed with rhino-orbital-cerebral infection caused by Alternaria infectoria. Cavernous sinus thromboses (CST) were seen in surgery, pathology, and MRI. She did not respond to potent antifungal therapy until the adding of anti-thrombosis drugs. By analyzing our case, together with the ones that have been published, we realized that fungal thrombosis in the cavernous sinus is the main pathophysiological problem in ROCM that typically shows mass enhancement within the cavernous sinus in radiographic images, thrombosis with characteristics of ischemia and infarction in pathology. Anticoagulation/antithrombus therapy might be helpful in the management of ROCM if potent antifungal treatment does not have effect.
IgE Generation and Mast Cell Activation
Authors: Kritas S.K. , Caraffa A. , Antinolfi P. , Saggini A. , Pantalone A. , Neri G. , Rosati M. , Tei M. , Speziali A. , Saggini R. , Pandolfi F. , Cerulli G. , Conti P.
Published: January 2017

IgE is an important marker for allergy and plays a central role in the induction of allergic diseases through its binding of the high affinity receptor on mast cells. Mast cells can influence B cell survival, proliferation and differentiation into CD138+cells. Among TH2 cytokines, interleukin (IL)-4 and IL-13 are responsible for class-switching in B cells which resolves in production of allergen-specific IgE antibodies that bind to specific receptor on mast cells. IgE synthesis by B cells is regulated by CD40 ligand, IL-4 and interferon-gamma, therefore inhibition of B cell antigen-specific IgE may prevent the cleavage of CD23 from B cells, having a therapeutic impact which also includes the removal of circulating free IgE, omalizumab, corticosteroids, mast cell stabilizers, leukotriene receptor antagonist, and others. B cell differentiation into IgE-producing cells requires two signals provided by TH2 cells and IL-4, however IL-4, IL-1 and IL-10 as well as several hormones are critical for the development of TH2 cells, while cytokines, such as interferon (IFN)-alpha, IFN-gamma, IL-12 and transforming growth factor (TGF)-beta play a negative role. However, the exact mechanism of this process has not yet been defined.
HIF-1α Provokes Delayed Neutrophil Apoptosis by Decreasing 24P3 Expression and Intracellular Iron Content
Authors: Pérez-Ladaga A. , Muñoz M.A. , Mastora C. , Sola A.
Published: January 2017

Neutrophil apoptosis is delayed in medical conditions associated to anoxia or hypoxia, prolonging tissue destruction and fostering the inflammation. Hypoxia Inducible Factor-1α (HIF-1α), is a main regulator of delayed neutrophil apoptosis but the mechanism of action is poorly characterized. Neutrophil gelatinase-associated lipocalin (24p3) participates actively in iron metabolism and the regulation of iron-responsive genes. Recently, a connection has been described between HIF-1α and 24p3. The purpose of the present study was to determine whether constitutive apoptosis in neutrophils requires 24p3 and whether HIF-1α represses 24p3 affecting cell death iron intracellular levels. To this end we used in vivo ischemic models and anoxic approaches based on the reactivation of the delayed apoptosis. We found that the stabilization of HIF-α during anoxic periods provoked a delay in neutrophil apoptosis through decrease of 24p3 expression and intracellular iron content. The ischemia drastically inhibited the synthesis of 24p3 in circulating neutrophils, increasing the tissue damage. Reactivation of neutrophil apoptosis with opsonized E.coli induced increases in intracellular levels of iron and 24p3. In conclusion, contrary to other cell types, constitutive apoptosis in neutrophils requires 24p3. During hypoxia or ischemia, HIF-1α stabilization represses 24p3 expression, consequently iron levels are depleted and neutrophil apoptosis is delayed.
Bifidobacteria BbC50 Fermentation Products Induce Human Cd4+ Regulatory T Cells with Antigen-Specific Activation and Bystander Suppression
Authors: Martin L. , Granier A. , Lemoine R. , Dauba A. , Vermeersch S. , Aubert-Jacquin C. , Baron C. , Lebranchu Y. , Hoarau C. , Velge-Roussel F.
Published: January 2017

Probiotic bacteria have been shown to have health benefits in various situations (inflammation, allergy, infection). We previously showed that a bacteria-free fermentation product of Bifidobacterium breve C50 (BbC50sn) induced high IL-10 secretion by human dendritic cells. As IL-10 is a regulatory cytokine, the aim of the present study was to examine whether DCs cultured in the presence of BbC50sn could induce regulatory T cells in an allogeneic context. Purified CD4+CD25− human T cells were co-cultured with allogeneic BbC50sn-treated dendritic cells for 4 weeks. The T cell population (BbC50sn-T) was analysed both at phenotypical and functional [ability to inhibit a mixed lymphocyte reaction (MLR)] levels. We showed that T lymphocytes acquired phenotype characteristics of regulatory T cells after 4 weeks of co-culture with BbC50sn-DCs, and inhibited in vitro T lymphocyte proliferation and IFN-γ production in an MLR. Transwell experiments demonstrated that this suppressive activity was not T cell contact-dependent but probably mediated by a soluble factor. Although BbC50sn-T cells secreted significant amounts of IL-10 and TGF-β, their suppressive effect is most likely not mediated through these cytokines. This is, to our knowledge, the first demonstration of in vitro regulatory T cell induction by a bacteria-free fermentation product in an allogeneic context.
Intravesical Hyaluronic Acid and Chondroitin Sulphate Improve Symptoms and Quality of Life in Patients with Late Radiation Tissue Cystitis: An Investigative Pilot Study
Authors: Sommariva M.L. , Lazzeri M. , Abrate A. , Guazzoni G. , Sandri S. , Montorsi F.
Published: January 2017

Intravesical hyaluronic acid (HA) and chondroitin sulphate (CS) instillation are effective for urinary tract infections (UTIs) and bladder pain syndrome. This study aimed to evaluate the tolerability, safety and efficacy of intravesical HA and CS instillation in patients with late radiation tissue cystitis (LRTC). In this pilot study, tolerability was reported as discontinuation or deviation of the protocol, safety as general or local side effects, efficacy as improvement of bladder capacity and frequency, quality of life (QoL) through the European Quality of Life 5-Dimensions (EQ-5D) (details at http://www.controlled-trials.com/ISRCTN37534393 ). Thirty-two patients with LRTC were enrolled. Twenty-seven patients (84.8%) received a mean of 12.2±0.3 months of instillation therapy. Only two patients (6.2%) developed a urinary tract infection from instillation, which required antibiotic treatment, nevertheless not compromising the therapy schedule. No male patient developed a urethral stricture. Intravesical instillation was associated with a significant increase (>50%) of bladder capacity from baseline (66.9ml) both at 3 months (101.9ml; p<0.001) and 12 months (174.4 ml; p<0.001). EQ-5D index significantly increased from baseline to both 3 and 12 months (0.26, 0.69 and 0.96, respectively; p<0.001). Intravesical co-administration of HA and CS improved bladder function, symptoms and QoL in patients with LRTC.
Rheumatoid Arthritis-like Disorder Mimicking Serum Sickness: Do Not Forget Acute B Hepatitis!
Authors: Famularo G. , Minisola G. , Gasbarrone I.
Published: January 2017

We report on a patient who presented with a severe symmetric polyarthritis that was found to be part of the prodromal stage of acute hepatitis B. This syndrome is seen in a minority of cases, resembles serum sickness and parallels the duration and level of hepatitis B viremia. It is a type III immune complex reaction with complement consumption and activation which ultimately triggers inflammation and may also occur in the context of other infections, vaccines, and use of antibiotics or sera. We emphasize the need to search for acute B hepatitis in all patients with polyarthritis or other symptoms of serum sickness.
Obesity, Inflammation and Neurological Alterations
Authors: Spinas E. , Saggini A. , Kritas S.K. , Cerulli G. , Caraffa A. , Antinolfi P. , Pantalone A. , Frydas A. , Tei M. , Speziali A. , Saggini R. , Conti P.
Published: January 2017

Inflammation, neurodegeneration, imbalance of neurotransmitter systems, oxidative stress and depression are all risk factors for obesity. There is evidence regarding the cross-talk between adipose tissue and the immune system and obese patients may show an alteration of immune functions with major depression, including immune suppression with reduced T-cell and macrophage activity. Obesity is mediated by inflammatory cells such as lymphocytes, macrophages and mast cells which release pro-inflammatory cytokines and chemokines. Obesity-induced leukocyte infiltrations in adipose tissue cause cytokine/chemokine release and inflammation. Here, we report the relationship between obesity, neurological alterations and inflammation.
The Relationship between Soluble Tumor Necrosis Factor-like Weak Inducer of Apoptosis Levels and Cardiac Functions in Peritoneal Dialysis Patients
Authors: Karadag S. , Gursu M. , Sakin A. , Atalay E. , Basinoglu F. , Aydin Z. , Uzun S. , Sumnu A. , Cebeci E. , Koldas M. , Ozturk S. , Kazancioglu R.
Published: January 2017

Tumor necrosis factor (TNF)-like weak inducer of apoptosis (sTWEAK) levels has been reported to be decreased in patients on hemodialysis (HD) and patients with heart failure. We aimed to study the relationship between sTWEAK levels and cardiac functions in peritoneal dialysis (PD) patients. This cross-sectional study was carried out on patients on chronic PD programs for more than three months. Patients aged under 18 or over 80 years, patients with overt cardiac disease, overt hypervolemia, active systemic infection, malignancy, peritonitis within the last month were excluded. The patient group was compared with the control group including healthy adults aged 24–61 years. Fifty-two PD patients were included in the study (mean age: 52.7±15.4 years; female/male ratio: 30/22). The corresponding data of the control group were 41.3±10.7 years and 17/14. There was no statistically significant difference between demographic parameters of the groups except age. The mean sTWEAK level of the patient and the control groups were similar (564±17 pcg/ml vs 535±126 pcg/ml, p=0.419). No correlation was detected between any of the demographic variables and sTWEAK levels. Among the echocardiographic parameters, only ejection fraction was found to be correlated negatively with sTWEAK levels. Patients with ischemic heart disease (IHD) and heart failure had significantly higher sTWEAK levels compared with the patients without these diseases. With linear regression analysis, only age and the presence of heart failure were found to be the independent determinants of sTWEAK levels. Level of sTWEAK is significantly high in PD patients with heart failure and IHD. sTWEAK may be a marker of cardiac functions in PD patients.
Evaluating the Murine Anti-Human Antibody Response and Assessment of General Activity and Cognition after Treatment with Human Intravenous Immunoglobulins in Healthy Adult C57/B6J Mice
Authors: Fülber I. , Bacher M. , Dodel R. , Röskam S.
Published: January 2017

Human intravenous immunoglobulin (IVIG) is a fractionated blood product that is used for the treatment of several autoimmune and immunodeficiency disorders. Recently, IVIG has been suggested for the treatment of Alzheimer's disease (AD). However, the molecular mode of action is still largely unknown. Therefore, preclinical assessment of the therapeutic efficacy of IVIG in animals may provide valuable information of the function of IVIG in vivo. However, it is recommended to determine the murine-anti-human antibody (MAHA) response in those animals before starting immunotherapy and subsequent assessment of the therapeutic efficacy in animal models for AD. After weekly administration of 400 μg IVIG in C57/B6J mice for the duration of twelve weeks, we found a significant increase of MAHA response against human IgG. Even after increased MAHA levels starting from week nine after treatment, there was no significant change in basic exploratory behavior, anxiety, and cognition. Therefore, it is suitable to study pharmacological and immunological activity, therapeutic efficacy, as well as mode of action of IVIG in animal models only for a short duration to avoid interference with IVIG treatment and neutralize possible therapeutic effects.
Honeycomb-like Structured Film Regulates Mediator Release from Non-Tumor Mast Cells
Authors: Sugimoto K. , Choi H. , Tanaka M.
Published: January 2017

We previously reported a honeycomb-like structured film (HCF) stimulates mast cell proliferation and multinucleated formation. In this study, we examined the role of HCF in regulating the release of mediators from cultured mast cells. We measured the release of histamine, substance P, tumor necrosis factor (TNF)-α, and leukotriene B4 (LTB-4) from NCL-2 cells (proliferative mouse non-tumor mast cells). After 7 days of culture, HCF selectively down-regulated the release of TNF-α, LTB-4, and (to a lesser extent) substance P, but not histamine. Mast cell attachment to HCF may have a greater effect on release of de novo synthesized molecules.
TLR4 and TLR9 Polymorphisms Effect on Inflammatory Response in End-Stage Renal Disease Patients
Authors: Santos-Martins M. , Sameiro-Faria M. , Ribeiro S. , Rocha-Pereira P. , Nascimento H. , Reis F. , Miranda V. , Quintanilha A. , Belo L. , Beirão I. , Santos-Silva A. , Bronze-Da-Rocha E. , Costa E.
Published: January 2017

Toll-like receptors (TLRs) play a key role in the response of innate and adaptive immune system to microbial and endogenous ligands. Inflammation is a common feature in end-stage renal disease (ESRD) patients; however, the mechanisms/factors triggering the inflammatory process are still poorly clarified. Our aim was to analyze the impact of the c.-1486T>C and c.896A>G polymorphisms in TLR9 and TLR4 genes, respectively, on the inflammatory response of ESRD patients. Clinical and laboratory evaluation was carried out on 184 ESRD patients. Polymerase chain reaction followed by restriction fragmens length polymorphisms (PCR-RFLP) was employed for genotyping of TLR-4 c.896A>G and TLR-9 c.-1486T>C polymorphisms. The prevalence of AA and AG of TLR4 c.896A>G polymorphism in ESRD patients was 97.8% and 2.2%, respectively. None of the individuals showed a homozygous TLR4 polymorphism. Concerning the TLR9 c.-1486T>C polymorphism, we found that ESRD patients showed a prevalence of TC and CC genotypes of 57.1% and 20.6%, respectively. We found that the heterozygous patients for the TLR4 c.896A>G polymorphism presented an increased level in lymphocyte count, a decrease in neutrophil/lymphocyte ratio and in serum levels of hepcidin. Regarding the TLR9 c.-1486T>C polymorphism, we found that it is associated with decreased white blood cell and neutrophil counts, ferritin and CRP serum levels, and with an increase in serum levels of creatinine. Our data suggest that the presence of the studied polymorphisms is associated with a decreased inflammatory response in ESRD patients under hemodialysis, and, thus its presence might have beneficial effects in ESRD patients. Moreover, our data provide new insights in the role of TLR polymorphisms in renal disease, which might have impact in the near future for the development of innovative therapies.
In vitro Study of BCG Granuloma Macrophage Morphofunctional Status
Authors: Shkurupy V.A. , Arkhipov S.A. , Akhramenko E.S. , Solomatina M.V. , Iljine D.A. , Neshchadim D.V.
Published: January 2017

We studied the morphofunctional and cytophysiological status of macrophages emigrating from BCG granulomas forming in spleen and free splenic macrophages that are not associated with granulomas. The experimental BCG granulomatosis was induced by intravenous injection of male BALB/c mice with BCG vaccine mycobacteria. The number of granulomas in spleen, their diameter, the proportion of granuloma macrophages with mycobacteria, the number of mycobacteria in granuloma macrophages, the proportion of live bacteria in granuloma macrophages and the number of granulomas macrophages capable of expressing IL-1α, TNF-α, GM-CSF were evaluated. BCG granulomas were explanted in cultures in vitro. Fractions, containing free splenic macrophages from BCG-infected animals, were explanted in separate cultures in vitro. The phagocytic activity of macrophages that migrated from BCG granulomas explanted in cultures one month after mycobacterial infection of mice, was much higher than those of splenic macrophages of intact mice. The phagocytic activity of free macrophages and macrophages from granulomas decreased with time after infection. By contrast, the antimycobacterial activity of free splenic macrophages and macrophages from BCG granulomas increased with time after infection. The correlational analysis showed that there are different correlational relationships between the number of granuloma macrophages expressing IL-1α, TNF-α, GM-CSF and phagocytic activity of macrophages from BCG granulomas. The results of the study are important for understanding the molecular and cellularmechanisms of development of chronic granulomatous inflammation induced by mycobacterial infection.
Design considerations of a randomized controlled trial of sedation level during hip fracture repair surgery: a strategy to reduce the incidence of postoperative delirium in elderly patients
Authors: Li Tianjing , Wieland L Susan , Oh Esther , Neufeld Karin J , Wang Nae-Yuh , Dickersin Kay , Sieber Frederick E
Published: January 2017

Background

Delirium is an acute change in mental status characterized by sudden onset, fluctuating course, inattention, disorganized thinking, and abnormal level of consciousness. The objective of the randomized controlled trial “A STrategy to Reduce the Incidence of Postoperative Delirium in Elderly Patients” (STRIDE) is to assess the effectiveness of light versus heavy sedation on delirium and other outcomes in elderly patients undergoing hip fracture repair surgery. Our goal is to describe the design considerations and lessons learned in planning and implementing the STRIDE trial.

Methods

Discussed are challenges encountered including (1) how to ensure that we quickly identify, assess the eligibility of, and randomize traumatic hip fracture patients; (2) how to implement interventions that involve continuous monitoring and adjustment during the surgery; and (3) how to measure and ascertain the primary outcome, delirium.

Results

To address the first challenge, we monitored the operating room schedule more actively than anticipated. We constructed and organized eligibility assessment data collection forms by purpose and by source of information needed to complete them. We decided that randomization needs to take place in the operating room. To address the second challenge, we designed and implemented a treatment protocol and covered the bispectral index monitor to prevent the Anesthesiologist/Anesthetist from being influenced by the bispectral index reading while administering the intervention. Finally, clinical assessment of delirium consisted of standardized interviews of the patient using validated instruments, interviews of those caring for the patient, and review of the medical record. A consensus panel made the final determination of a delirium diagnosis. We note that STRIDE is a single-center trial. The decisions we took may have different implications for multi-center trials.

Conclusions

Lessons learned are likely to provide useful information to others designing trials in emergency and surgical setting and for those who are interested in unbiased assessment of delirium.
Leading through ritual: Ceremony and emperorship in early modern China
Authors: Islam Gazi , Keliher Macabe
Published: January 2017

Ritual performance is well understood in organizational maintenance. Its role in leadership and processes of change, however, remains understudied. We argue that ritual addresses key challenges in institutionalizing leadership, particularly in fixing the relation between a charismatic leader and formal governance structures. Through a historical case study of the institutionalization of the emperor in Qing China (1636–1912), we argue that the shaping of collective understandings of the new emperor involved structural aspects of ritual that worked through analogical reasoning to internalize the figure of the leader through focusing attention, fixing memory, and emotionally investing members in the leader. We argue that data from the Qing dynasty Board of Rites show that ritual was explicitly designed to model the new institutional order, which Qing state-makers used to establish collective adherence to the emperorship. We further discuss the implications of this case for understanding the symbolic and performative nature of leadership as an institutional process.
Protective mechanical ventilation in United Kingdom critical care units: A multicentre audit
Authors: Newell Christopher P , Martin Matthew J , Richardson Neil , Bourdeaux Christopher P
Published: January 2017

Lung protective ventilation is becoming increasingly used for all critically ill patients being mechanically ventilated on a mandatory ventilator mode. Compliance with the universal application of this ventilation strategy in intensive care units in the United Kingdom is unknown. This 24-h audit of ventilation practice took place in 16 intensive care units in two regions of the United Kingdom. The mean tidal volume for all patients being ventilated on a mandatory ventilator mode was 7.2(±1.4) ml kg−1 predicted body weight and overall compliance with low tidal volume ventilation (≤6.5 ml kg−1 predicted body weight) was 34%. The mean tidal volume for patients ventilated with volume-controlled ventilation was 7.0(±1.2) ml kg−1 predicted body weight and 7.9(±1.8) ml kg−1 predicted body weight for pressure-controlled ventilation ( P < 0.0001). Overall compliance with recommended levels of positive end-expiratory pressure was 72%. Significant variation in practice existed both at a regional and individual unit level.
Using a Discrete Choice Conjoint Experiment to Engage Stakeholders in the Design of an Outpatient Children’s Health Center
Authors: Cunningham Charles E. , Niccols Alison , Rimas Heather , Robicheau Randi , Anderson Colleen , DeVries Bart
Published: January 2017

Objectives:

To engage users in the design of a regional child and youth health center.

Background:

The perspective of users should be an integral component of a patient-centered, evidence-based approach to the design of health facilities.

Methods:

We conducted a discrete choice conjoint experiment (DCE), a method from marketing research and health economics, as a component of a strategy to engage users in the preconstruction planning process. A sample of 467 participants (290 staff and 177 clients or community stakeholders) completed the DCE.

Results:

Latent class analysis identified three segments with different design preferences. A group we termed an enhanced design (57%) segment preferred a fully featured facility with personal contacts at the start of visits (in-person check-in, personal waiting room notification, volunteer-assisted wayfinding, and visible security), a family resource center with a health librarian, and an outdoor playground equipped with covered heated pathways. The self-guided design segment (11%), in contrast, preferred a design allowing a more independent use of the facility (e.g., self-check-in at computer kiosks, color-coded wayfinding, and a self-guided family resource center). Designs affording privacy and personal contact with staff were important to the private design segment (32%). The theme and decor of the building was less important than interactive features and personal contacts.

Conclusion:

A DCE allowed us to engage users in the planning process by estimating the value of individual design elements, identifying segments with differing views, informing decisions regarding design trade-offs, and simulating user response to design options.
Arthroscopic Reduction and Internal Fixation (ARIF) of a Comminuted Posterior Talar Body Fracture: Surgical Technique and Case Report
Authors: Kadakia Rishin , Konopka Jeff , Rodik Tristan , Ahmed Samra , Labib Sameh A
Published: January 2017

The talus is the second most common fractured tarsal bone. While their incidence may be low, talus fractures are severe injuries that can lead to long-term disability and pain. Displaced talar body fractures are typically treated through an open approach with the aim of obtaining anatomic reduction and stable fixation. There are several case reports in the literature demonstrating successful management of talus fractures arthroscopically. An arthroscopic approach minimizes soft tissue trauma, which can help decrease postoperative wound complications and infections. In this article, the authors describe a surgical technique of an arthroscopic reduction and internal fixation of a comminuted posterior talar body fracture. Compared with an open posterior approach with or without osteotomies, an arthroscopic technique improved visualization and allowed precise reduction and fixation.

Levels of Evidence: Level V: Case report
Modulation of Gene Expression in Infrapatellar Fat Pad–Derived Mesenchymal Stem Cells in Osteoarthritis
Authors: Bravo Beatriz , Argüello Jose Manuel , Gortazar Arancha R. , Forriol Francisco , Vaquero Javier
Published: January 2017

Aim

In the osteoarthritis (OA) disease, all structures of the joint are involved. The infrapatellar Hoffa fat pad is rich in macrophages and granulocytes, which also represents a source of adipose mesenchymal progenitor cells (ASC) cells. In our study, we analyze how OA affects the ability of ASC-derived from Hoffa’s fat pad to differentiate into chondrocytes.

Material and methodology

We took knee Hoffa’s pad samples and adipose tissue from the proximal thigh from 6 patients diagnosed with severe OA and from another 6 patients with an anterior cruciate ligament (ACL) rupture without OA. From all the patients, we took subcutaneous adipose tissue from the thigh, as the control group. Samples of synovial fluid (SF) were also extracted. The gene expression was analyzed by real-time quantitative polymerase chain reaction.

Results

PTH1R and MMP13 expression during chondrogenic differentiation were similar between OA and ACL groups, while the expression of OPG, FGF2, TGFβ, MMP3 were significantly lower in the OA group. Exposure of differentiated ASC to OA SF induced an increase in the expression of OPG, PTH1R, and MMP13 and a decrease in the expression of FGF2 in cell culture of the ACL group. However, expression of none of these factors was altered by the OA synovial fluid in ASC cells of the OA group.

Conclusion

OA of the knee also affects the mesenchymal stem cells of Hoffa fat, suggesting that Hoffa fat is a new actor in the OA degenerative process that can contribute to the origin, onset, and progression of the disease.
α-Lipoic Acid Potentiates the Anti-Inflammatory Activity of Avocado/Soybean Unsaponifiables in Chondrocyte Cultures
Authors: Frondoza Carmelita G. , Fortuno Lowella V. , Grzanna Mark W. , Ownby Stacy L. , Au Angela Y. , Rashmir-Raven Ann M.
Published: January 2017

Objective

Pro-inflammatory mediators such as prostaglandin E-2 (PGE2) play major roles in the pathogenesis of osteoarthritis (OA). Although current pharmacologic treatments reduce inflammation, their prolonged use is associated with deleterious side effects prompting the search for safer and effective alternative strategies. The present study evaluated whether chondrocyte production of PGE2 can be suppressed by the combination of avocado/soybean unsaponifiables (ASU) and α-lipoic acid (LA).

Design

Chondrocytes from articular cartilage of equine joints were incubated for 24 hours with: (1) control media, (2) ASU, (3) LA, or (4) ASU + LA combination. Cells were activated with lipopolysaccharide (LPS), interleukin 1β (IL-1β) or hydrogen peroxide (H2O2) for 24 hours and supernatants were immunoassayed for PGE2. Nuclear factor-kappa B (NF-κB) analyses were performed by immunocytochemistry and Western blot following 1 hour of activation with IL-1β.

Results

LPS, IL-1β, or H2O2 significantly increased PGE2 production. ASU or LA alone suppressed PGE2 production in LPS and IL-1β activated cells. Only LA alone at 2.5 µg/mL was inhibitory in H2O2-activated chondrocytes. ASU + LA inhibited more than either agent alone in all activated cells. ASU + LA also inhibited the IL-1β induced nuclear translocation of NF-κB.

Conclusions

The present study provides evidence that chondrocyte PGE2 production can be inhibited by the combination of ASU + LA more effectively than either ASU or LA alone. Inhibition of PGE2 production is associated with the suppression of NF-κB translocation. The potent inhibitory effect of ASU + LA on PGE2 production could offer a potential advantage for a combination anti-inflammatory/antioxidant approach in the management of OA.
Learn It, Buy It, Work It: Intensive Pregnancy on Instagram
Authors: Tiidenberg Katrin , Baym Nancy K.
Published: January 2017

This article analyzes how pregnant women perform their pregnancies on Instagram. We ask whether they rely on and reproduce pre-existing discourses aimed at morally regulating pregnancy, or reject them and construct their own alternatives. Pregnancy today is highly visible, intensely surveilled, marketed as a consumer identity, and feverishly stalked in its celebrity manifestations. This propagates narrow visions of what a “normal” pregnancy or “normal” pregnant woman should be like. We argue that pregnant women on Instagram do pregnancy via three overlapping and complimentary discourses of “learn it,” “buy it,” and “work it.” Together these form the current authoritative knowledge of pregnancy we call “intensive pregnancy” as performed on Instagram. Concurrently, this article highlights how the combined discursive power of hashtags, images, and captions may influence and enforce discursive hegemonies.
A Hashtag Worth a Thousand Words: Discursive Strategies Around #JeNeSuisPasCharlie After the 2015 Charlie Hebdo Shooting
Authors: Giglietto Fabio , Lee Yenn
Published: January 2017

Following a shooting attack by two self-proclaimed Islamist gunmen at the offices of French satirical weekly Charlie Hebdo on 7 January 2015, there emerged the hashtag #JeSuisCharlie on Twitter as an expression of solidarity and support for the magazine’s right to free speech. Almost simultaneously, however, there was also #JeNeSuisPasCharlie explicitly countering the former, affirmative hashtag. Based on a multimethod analysis of 74,047 tweets containing #JeNeSuisPasCharlie posted between 7 and 11 January, this article reveals that users of the hashtag under study employed various discursive strategies and tactics to challenge the mainstream framing of the shooting as the universal value of freedom of expression being threatened by religious extremism, while protecting themselves from the risk of being viewed as disrespecting victims or endorsing the violence committed. The significance of this study is twofold. First, it extends the literature on strategic speech acts by examining how such acts take place in a social media context. Second, it highlights the need for a multidimensional and reflective methodology when dealing with data mined from social media.
Initial Preoperative Management of Geriatric Hip Fractures
Authors: Ikpeze Tochukwu C. , Mohney Stephen , Elfar John C.
Published: January 2017

Hip fractures are a common emergency among the geriatric population and often requires immediate hospitalization for proper assessment. More than 90% of the time, hip fractures are suffered by individuals older than 65 and are usually precipitated predominantly by falls. Current studies show that the average individual over 65 years falls at least once a year, and roughly 1 out of every 4 of these individuals succumb to their injuries just 12 months following surgical treatment. Moreover, timely treatment and management of these hip fractures have shown to decrease mortality by reducing cardiopulmonary and venous thromboembolic complications that often accompany hip surgeries. As a result, an emphasis on initial preoperative assessment is important to help identify the presence of ancillary factors such as preexisting comorbidities, which can impact the course of treatment. Delaying surgical management of hip fractures has been linked to decreased functional outcomes and increased mortality rates. Time, rather than technique, appears to be a recurring factor that can impact the long-term survival of these patients. The initial preoperative assessment, therefore, presents a window of opportunity where possible interventions can be made in an effort to reduce the delay of surgery, minimize postsurgical complications, and ultimately improve mortality rate among patients with hip fracture.