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The interaction mechanism of spherical gold nanoparticles (AuNPs) and rod-shaped gold nanoparticles (AuNRs) with γ-globulin and hemoglobin was comprehensively and comparatively analyzed. γ-Globulin and hemoglobin have high affinity with AuNPs, and with two different types of binding sites on AuNRs surface. Except hemoglobin interaction with the first binding site of AuNRs, the interaction between γ-globulin/hemoglobin and AuNPs/AuNRs is the spontaneous, endothermic and entropy-driven process, and hydrophobic interaction plays a dominant role. The molecular adsorption mechanism of γ-globulin/hemoglobin on AuNPs and AuNRs surface conforms to Langmuir model and Freundlich model, respectively. The kinetic molecular mechanism between them conforms to the pseudo-second-order model, and chemisorption is the rate-limiting step. AuNPs result in the loosening and unfolding of γ-globulin backbone. AuNRs have no significant effect on γ-globulin backbone. AuNPs/AuNRs result in no significant changes in hemoglobin structure and heme group microenvironment. AuNPs/AuNRs decrease the hydrophobicity of Trp microenvironment of γ-globulin, but there is an intramolecular energy transfer from Trp residue to Tyr residue of hemoglobin. The β-sheet of γ-globulin and the α-helix of hemoglobin reduce by increasing concentrations of AuNPs/AuNRs. Molecular docking is suggesting that the specific amino acid residues of γ-globulin and hemoglobin interaction with AuNPs/AuNRs, and validates the experimental results., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Red tide events, caused by a toxin producing dinoflagellate, Karenia brevis, occur annually in Florida and Texas. These events lead to health risks for both humans and wildlife that utilize coastal environments. Brevetoxins, potent lipophilic neurotoxins produced by K. brevis, modulate immune responses in laboratory studies with model organisms and in the natural environment in both humans and wildlife. Studies show that brevetoxins activate immune cells, stimulate production of gamma-globulins, cytokines, and neutrophils, modulate lysozyme activity, induce apoptosis, and modulate lymphocyte proliferation in marine species. The objective of this review was to summarize brevetoxin-induced immunotoxicity in marine animals based on available peer-reviewed literature about K. brevis blooms and associated health concerns and propose putative toxicity pathways. This review identifies knowledge gaps within current brevetoxin induced immunotoxicity research, including assessing the long-term impacts of brevetoxin exposure, elucidating the mechanistic linkages between brevetoxins and immune cells, and evaluating repeated and chronic versus acute brevetoxin exposure implications on overall organismal health. The putative immunotoxicity pathways based on evidence from brevetoxin-exposure in marine fauna described in this review represent a useful tool and resource for researchers, wildlife managers, and policy makers. This review and proposed putative immunotoxicity pathways will inform decisions regarding the risks of algal blooms, as it pertains to marine animal health., Competing Interests: Declaration of Competing Interest The authors do not declare any conflicts of interest., (Copyright © 2022. Published by Elsevier B.V.)

It is well documented that choline is known as one of the essential ingredients of phospholipids. Choline acts as a determinative element for appropriate cell membrane functions. On the other hand α-tocopherol (Vit E) is a fat-soluble vitamin. This vitamin acts as a strong antioxidant in the living body's defense system against oxidative stress. Lipid peroxidation in peripartum and early lactating cows is significantly increased while the level of serum Vit E is decreases dramatically. These concomitant physiological changes demonstrate a higher level of oxidative stress subsequently leads to serious health issues in dairy cows. Therefore, the present research was designed to investigate the following items in dairy cattle: 1) evaluation of the possible changes in serum protein fractions, and 2) comparing the oxidative status of orally RPC and vitamin E supplementation in dairy cows in early lactation period. In the current study 30 early lactating primiparous and multiparous Holstein cows (body condition score (BCS)=2.51 ± 0.10) were used beginning five weeks postpartum. All the animals were randomly divided in to three groups (n=10) (number of lactation=2.61). The animals were randomly assigned to receive one of the following treatments. Group 1 served as control group were not received any supplement. The second group was supplemented with 90 g/d of RPC (Reashre Choline, Balchem, USA). The third group was administrated 4400 IU/d vitamin E (Roche, Vitamins Ltd; Switzerland). In the current study, serum protein electrophoresis showed four main fractions as follows: albumin, α-globulin, β-globulin, and γ-globulin. The recorded data showed that the percentages of albumin and γ-globulin fractions were higher in treated groups compared to the control group. In the animals supplementing with RPC and vitamin E the percentages of serum albumin increased to the value of 37. 70±1.63 and 38.21±1.28 respectively compare to the control group (34.69±1.21), which were significant ( P <0.05).

A cannabidiol (CBD) oral solution (Epidiolex®) has been approved by the United States Food and Drug Administration to treat seizure conditions. However, the biomedical and pharmaceutical applications of CBD are hindered partially due to a limited understanding of CBD's pharmacokinetic behaviors, such as its interactions with plasma proteins. Herein, we investigated the molecular interactions between CBD and two plasma proteins, namely, human serum albumin (HSA) and γ-globulin, using biophysical techniques including surface plasmon resonance (SPR), isothermal titration calorimetry, and differential scanning calorimetry, as well as molecular docking. CBD bound to HSA and γ-globulin in an exothermic manner (enthalpy: -9.3 ×10 4 and -3.7 ×10 4 kcal/mol, respectively) with a binding affinity of 1.8 × 10 -5 and 1.3 × 10 -5 M, respectively. The binding ratio between CBD and HSA or γ-globulin was approximately 1:1 and 3:1, respectively. Furthermore, computational modeling suggested that CBD and warfarin may bind to HSA independently, supported by data from a competitive SPR binding assay. Findings from the current study elucidate CBD's plasma protein binding characteristics and shed light on their impact on CBD's pharmacokinetic property., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Immunoglobulin replacement therapy is recommended in case of severe hypogammaglobulinemia after allogeneic hematopoietic stem cell transplantation (allo-HSCT). However, the supposed increased risk of infection in case of hypogammaglobulinemia has not been confirmed in allo-HSCT. In this study, we assessed the relationship between the gamma globulin level and the risk of infection during the 100 days following the allo-HSCT., Methods: We gathered the weekly laboratory tests from day 7 to day 100 of 76 allograft patients, giving a total of 1 044 tests. 130 infections were documented clinically, by imaging, or microbiologically., Results: Average gamma globulin levels between D-7 and D100 did not differ between patients with or without infection (642 ± 232 and 671 ± 246 mg/dL, respectively, P = .65). Gamma globulin level <400 mg/dl was not associated with the occurrence of infection between the test studied and the next one (aOR 1.33 [0.84-2.15], P = .24). The gamma globulin level was not predictive of bacterial or fungal infections (AUC 0.54 [95%CI: 0.47-0.61]) nor of viral reactivations (AUC 0.51 [95%CI: 0.43-0.60])., Conclusions: This confirmed that the humoral deficiency is a minor part of the immune deficiency in the 100 days post-transplant. This questions the relevance of the indications of immunoglobulin substitution during this period., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

The pattern of serum proteins, the typical features of the electrophoretogram in newborn piglets and during their postnatal development is not completely described. Therefore, the aim of this study was to characterize the changes in serum protein electrophoretic pattern and features of the electrophoretograms during the early postnatal period. Significant changes during the monitored period were found in all evaluated parameters (P < 0.001). The most marked changes were observed mainly in the period before weaning. The concentrations of total proteins, albumin and γ-globulins were before colostrum intake low, γ-globulins represented the smallest proportion of protein fractions. The proportion of α 1 -globulins was after birth a dominant protein fraction. Significant increase of total proteins, α 2 -, β- and γ-globulins and decrease of α 1 -globulins was found 2 days after colostrum intake. The albumin and A/G values increased after birth gradually until weaning. After weaning a significant changes were found in absolute concentrations of total protein and albumin, and in relative values of β-globulin fractions. Presented results showed marked developmental alterations in the serum protein pattern in piglets along with the age. The study also brings new knowledge in the field of description of typical features of electrophoretograms in the observed period of piglet's life., (© 2021. The Author(s).)

Plasma proteins play a fundamental role in living organisms. They participate in the transport of endogenous and exogenous substances, especially drugs. 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium salts, have been synthesized as potential anticancer substances used for cancer treatment. Most anticancer substances generate a toxic effect on the human body. In order to check the toxicity and therapeutic dosage of these chemicals, the study of ligand binding to plasma proteins is very relevant. The present work presents the first comparative analysis of the binding of one of the 5-alkyl-12(H)-quino[3,4-b][1,4]benzothiazinium derivatives (Salt1) with human serum albumin (HSA), α-1-acid glycoprotein (AGP) and human gamma globulin (HGG), assessed using fluorescence, UV-Vis and CD spectroscopy. In order to mimic in vivo ligand-protein binding, control normal serum (CNS) was used. Based on the obtained data, the Salt1 binding sites in the tertiary structure of all plasma proteins and control normal serum were identified. Both the association constants (K a ) and the number of binding site classes ( n ) were calculated using the Klotz method. The strongest complex formed was Salt1-AGP complex (K a = 7.35·10 4 and 7.86·10 4 mol·L -1 at excitation wavelengths λ ex of 275 and 295 nm, respectively). Lower values were obtained for Salt1-HSA complex (K a = 2.45·10 4 and 2.71·10 4 mol·L -1 ) and Salt1-HGG complex (K a = 1.41·10 4 and 1.33·10 4 mol·L -1 ) at excitation wavelengths λ ex of 275 and 295 nm, respectively, which is a positive phenomenon and contributes to the prolonged action of the drug. Salt1 probably binds to the HSA molecule in Sudlow sites I and II; for the remaining plasma proteins studied, only one binding site was observed. Moreover, using circular dichroism (CD), fluorescence and UV-Vis spectroscopy, no effect on the secondary and tertiary structures of proteins in the absence or presence of Salt1 has been demonstrated. Despite the fact that the conducted studies are basic, from the scientific point of view they are novel and encourage further in vitro and in vivo investigations. As a next part of the study (Part 2), the second new synthetized quinobenzothiazine derivative (Salt2) will be analyzed and published.

Patients with haematological malignancies are considered to be a risk group for developing severe Coronavirus disease (Covid-19). Because of the limitations of therapeutic options, the development of new treatment strategies is mandatory, such as convalescent plasma (CP). Herein we report the use of CP therapy as an off-label indication in two lymphoma patients with relapsed COVID-19 in the setting of low gammaglobulin levels because of previous rituximab chemo-immunotherapy. Both were PCR positive for SARS-CoV-2 but had an absence of antibodies to the virus more than one month later of symptoms initiation. They developed important respiratory and neurological complications. After CP infusion, neutralising antibodies were detected and viral load dissapeared in both patients leading to clinical improvement with no more Covid-19 relapse., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Dogs are the main reservoir hosts of Leishmania infantum; nevertheless, recent investigations indicate a likely role for cats in the epidemiology of Leishmania infection. Feline leishmaniosis (FeL) remains poorly characterised, partly due to the lack of suitable diagnostic tools. This study aimed to compare serum amyloid A (SAA) levels and serum protein electrophoresis (SPE) profiles (specifically, alpha 2 and gamma globulins) in cats naturally exposed to or infected by L. infantum from southern Italy versus those of healthy controls and versus cats with neoplastic or inflammatory conditions from non-endemic areas., Methods: Serum or plasma samples from four cohorts of cats were analysed for SAA levels and by SPE: (i) G1: healthy controls from Leishmania-non-endemic regions of Switzerland; (ii) G2: cats pre-diagnosed with neoplastic or inflammatory conditions available from the University of Cambridge sample archive; (iii) G3: L. infantum-seropositive, quantitative (q)PCR-negative cats from southern Italy; (iv) G4: L. infantum-seropositive and qPCR-positive cats from southern Italy. SAA data were assessed for normality and homoscedasticity using the Shapiro-Wilk and Levene's tests, respectively; the Kruskall-Wallis test, followed by Dunn's test with Bonferroni correction were subsequently used to compare SAA serum levels between groups. A weighted generalised linear model with a binomial distribution was used to assess statistically significant differences in the numbers of animals displaying elevated gamma globulins and increased alpha 2 globulins between groups., Results: Overall, 68 samples were analysed (G1: n = 16, G2: n = 20, G3: n = 20, G4: n = 12). Cats suffering from neoplastic and inflammatory conditions (G2 ) showed significantly higher SAA levels than healthy controls (G1) (median values [interquartile range]: G1: 0.00 [0.00-0.00] mg/l versus G2: 0.85 [0.00-49.55] mg/l). G2, G3 and G4 cats showed higher percentages of individuals with increased alpha 2 globulins (percentages ± standard error: G1 = 20.0% ± 10.3, G2 = 80.0% ± 8.9, G3 = 70.0% ± 10.2, G4 = 75.0% ± 12.5) and gamma globulins (G1 = 0.0% ± 0, G2 = 65.0% ± 10.7, G3 = 50.0% ± 11.2, G4 = 58.3% ± 14.2) than healthy control cats (G1). For all three markers, no significant difference between cats within G2, G3 and G4 was recorded., Conclusions: This study indicates that the proportions of animals with elevated levels of alpha 2 and gamma globulins are significantly higher in cats exposed to and infected with L. infantum. Levels of SAA and alpha 2 and gamma globulins may not be used to differentiate between L. infantum infection or exposure, and neoplastic and/or inflammatory conditions.

This research paper addresses the hypothesis that an oral supplementation with organically modified clinoptilolite will improve colostrum quality in primiparous dairy cows whilst having no adverse effects on the cows' health. A total of 36 pregnant Holstein primiparous dairy cattle were randomly assigned to receive daily oral drenching, two hours following morning feeding, with 1 l of water containing either 0 g/l (n = 16) or 150 g/l (n = 20) of clinoptilolite. Treatment lasted from 24 ± 4 d prior to expected parturition until two days postpartum (pp). Colostrum was collected at 2 to 3 h, 12, 24 and 36 h pp and blood samples were collected at 24 ± 4 and 4 ± 2 d prior to parturition and 1, 2 and 7 d pp. Overall mean dry matter, fat and total protein percentage as well as IgG concentration and mass were significantly greater in colostrum collected from cattle drenched with clinoptilolite (total protein increased by 15% and IgG concentration and mass by 21 and 38% respectively at first sampling and further at second sampling). Total γ globulin and most other blood serum biochemistry parameters did not differ between cattle treated and not treated with clinoptilolite, the only exception being the fast anionic γ globulin fraction that was 17% greater at 4 ± 2 d prior to parturition and 10% lower on the 1st day pp in treated cattle. These results showed that organically modified oral clinoptilolite supplementation at 150 g/d significantly increases the IgG concentration in colostrum and has no adverse effects on the energy status, protein, lipid, and mineral metabolism in primiparous dairy cattle during prepartum period.

The present work is aimed at investigating the chemicophysical properties of the interface between silicone oils (SOs) used in vitreoretinal surgery and aqueous solutions, in the presence of surfactant biomolecules. Such molecules are thought to play an important role in the formation of SO emulsions in vitrectomised eyes, in which the natural vitreous body has been replaced with a SO. In particular, we have measured the interfacial tension (IT) and the interfacial dilational viscoelasticity (DV) of the interface between SO (Siluron 1000) and serum proteins (albumin and γ -globulins) at various concentrations in a Dulbecco alkaline buffer. The equilibrium IT value is relevant for the onset of emulsification, and the DV influences the stability of an emulsion, once formed. The study is complemented by preliminary emulsification tests. The experimental results show that, when proteins are dissolved in the aqueous solution, the rheological properties of the interface change. The IT decreases significantly for physiological protein concentrations, and the DV modulus achieves high values, even for small protein concentrations. The emulsification tests confirm that, in the presence of proteins, emulsions are stable on the time scale of months. We conclude that the measured values of IT in the presence of serum proteins are compatible with the promotion of droplet formation, which, in addition, are expected to be stable against coalescence. Adsorption of biomolecules at the interface with the SO is, therefore, likely to play an important role in the generation of an emulsion in eyes subjected to vitrectomy. These findings are relevant to identify strategies to avoid or control the formation of emulsions in eyes., Competing Interests: The authors declare that there is no conflict of interest regarding the publication of this paper., (Copyright © 2020 Irene Nepita et al.)

Adenosine A 3 receptor (A 3 R) is a promising drug target cancer and for a number of other conditions like inflammatory diseases, including asthma and rheumatoid arthritis, glaucoma, chronic obstructive pulmonary disease, and ischemic injury. Currently, there is no experimentally determined structure of A 3 R. We explored the binding profile of O4-{[3-(2,6-dichlorophenyl)-5-methylisoxazol-4-yl]carbonyl}-2-methyl-1,3-thiazole-4-carbohydroximamide (K18), which is a new specific and competitive antagonist at the orthosteric binding site of A 3 R. MD simulations and MM-GBSA calculations of the WT A 3 R in complex with K18 combined with in vitro mutagenic studies show that the most plausible binding conformation for the dichlorophenyl group of K18 is oriented toward trans-membrane helices (TM) 5, 6 and reveal important residues for binding. Further, MM-GBSA calculations distinguish mutations that reduce or maintain or increase antagonistic activity. Our studies show that selectivity of K18 toward A 3 R is defined not only by direct interactions with residues within the orthosteric binding area but also by remote residues playing a significant role. Although V169 5.30 is considered to be a selectivity filter for A 3 R binders, when it was mutated to glutamic acid, K18 maintained antagonistic potency, in agreement with our previous results obtained for agonists binding profile investigation. Mutation of the direct interacting residue L90 3.32 in the low region and the remote L264 7.35 in the middle/upper region to alanine increases antagonistic potency, suggesting an empty space in the orthosteric area available for increasing antagonist potency. These results approve the computational model for the description of K18 binding at A 3 R, which we previously performed for agonists binding to A 3 R, and the design of more effective antagonists based on K18.

Exploration of simple and universal methods to quantitatively measure nanoparticle (NP)-protein interaction is of great importance. In this work, pulsed streaming potential (SP) measurement has been used to evaluate the interaction between NPs and proteins within microchannels. Graphene oxide (GO) and SiO 2 NPs were selected to represent two kinds of NPs. Lysozyme and common blood proteins, including albumin V, γ-globulins, and fibrinogen, were used as model proteins. The linear relationship between the initial adsorption rate ( S = d E r /d t ) and the concentration of proteins was observed. Combined with the Hill equation, the microscopic dissociation constant ( K D ) and the Hill coefficient ( n ) between NPs and proteins were calculated based on the relationship between S and the concentration of each protein. The concentration of free proteins which have not interacted with the NPs in the NPs-protein mixture could also be measured. The influence of pH, conductivity, and ionic strengths of the incubation buffer on the interaction between GO and lysozyme was evaluated based on the constant K D . The interaction intensity between NPs and proteins was defined as charge neutralization efficiency Q C , which could be calculated from the value of S . It takes only 150 s to get the whole set of data under the optimized experiment parameters. The measurement solely depends on the surface charge, no intrinsic fluorescence is required for either the NPs or the proteins, and no labeling or immobilization process is involved as well.

Background: Loss of response to anti-TNFα treatment occurs frequently in IBD- patients. We evaluatedthe predictive value of serum albumin and γ-globulin concentrations for treatment failure., Methods: Prospectively, all patients treated for the first time with either infliximab or adalimumab for IBD between 2007 and 2018 were included. All patients were tested for serum albumin and γ-globulin concentrations and were followed up until June 2018., Results: 128 patients (95 Crohn's disease, 67 females, age 40.1 ± 13.7 years) were included in the study. 81patients (63.3%) received infliximab and 47 (36.7%) adalimumab first line. Eight patients (6.3%) were primary non-responders, 50 patients (39.0%) showed a sustained clinical remission and 70 patients (54.7%) developed a secondary loss of response. Meantime to develop secondary loss of response was 24.5 ± 20.5 months. Albumin serum concentrations in the clinical response group were significantly higher than in the secondary loss of response group (39.8 ± 5.7 g/L vs. 35.0 ± 5.4 g/L). γ-globulin serum concentrations in the sustained response group were significantly lower than in the secondary loss of response group (11.8 ± 2.8 g/L vs. 14.7 ± 4.5 g/L). Hypoalbuminemia and hypergammaglobulinemia were associated with the loss of response. Immunosuppressant co-medication in patients with high γ-globulin serum concentrations reduced the risk of secondary loss of response., Conclusion: Low albumin and increased γ-globulin serum concentrations are strongly associated with a higher risk for loss of response to an anti-TNFα treatment. Increased serum γ-globulin concentrations may have a higher risk to produce anti-drug antibodies or a different phenotype of disease less responsive to anti-TNFα treatment.

Plasma protein binding (PPB) can be different depending on the status of hepatic or renal functions. In this study, the PPB of lenvatinib was determined using equilibrium dialysis in plasma from healthy volunteers and from subjects with mild, moderate, or severe hepatic impairment or renal impairment. Plasma from these subjects, fortified with lenvatinib at four concentrations (20, 200, 500, or 1200 ng/ml), was dialysed against phosphate buffered saline (PBS), and then determinations of the total concentrations of lenvatinib in plasma and unbound concentrations in PBS were made. In addition, the binding of lenvatinib was determined in human serum albumin (HSA), α 1 -acid glycoprotein (AAG), and human γ-globulin (HG) in order to identify major binding proteins in human plasma. The PPB of lenvatinib in subjects with HI or RI ranged from 97.5% to 98.2% in hepatic impairment and 98.0% to 98.4% in renal impairment, which was similar to that of healthy volunteers. The binding of lenvatinib to HSA, AAG, and HG was 96.6%-97.1%, 46.4%-69.9%, and 19.1%-23.9%, respectively. These findings suggest that lenvatinib mainly binds to HSA and neither renal nor hepatic impairment impacts the PPB of lenvatinib., (© 2019 John Wiley & Sons, Ltd.)

Objective: To determine altered manifestation of plasma proteins in X-rays technicians who are regularly exposed to low doses of radiations over a long period during their job., Study Design: Descriptive study., Place and Duration of Study: District Headquarters Hospital and Mufti Mahmood Memorial Teaching Hospital; from January 2017 to January 2018., Methodology: The study enrolled 70 individuals consisting of 50 X-ray technicians working 8 to 12 hours/day for five days per week and 20 unexposed healthy controls. The serum protein expression pattern (concentrations of various serum proteins) was evaluated through cellulose acetate electrophoresis and serum antioxidant status was measured through ferric reducing ability of plasma (FRAP) assay., Results: The antioxidant assay showed significantly low trolox-equivalent antioxidant capacity (TEAC) status and FRAP value in X-ray technicians as compared to controls (p<0.001). Analysis of serum protein demonstrated a significantly reduced concentrations of albumin (p<0.001) and elevated level of the Ɣ-globulins (p<0.001), while other globulins fractions like α1 and β remain unchanged. There was a strong negative correlation (p<0.001) according to Pearson coefficient (r=87%⁽⁻⁾) between albumin and Ɣ-globulins fraction. Whereas, a positive correlation (p<0.001) (r=46%⁽⁺⁾) between alpha 1 globulin and albumin fraction was observed. A correlation between other globulin fractions and albumin was found statistically significant (p<0.001)., Conclusion: Elevated serum gamma globulins may be a potential protein biomarker for triage and detection of X-radiation induced damages.

Objective: The production of antibody, also referred immunoglobulin, is the principal functions of B cells. Gamma globulin fraction determined by serum protein electrophoresis is composed almost entirely of immunoglobulin. This study aimed to investigate the association between gamma globulin level and oncological outcomes in patients with nonmuscle-invasive bladder cancer (NMIBC)., Patients and Methods: A total of 274 patients with NMIBC who underwent transurethral surgery between 2000 and 2015 were identified. One hundred forty-four patients (52.6%) had received adjuvant intravesical bacillus Calmette-Guérin. Gamma globulin fraction (%) was determined by serum protein electrophoresis, and gamma globulin level (mg/dl) was calculated by multiplying the total protein level (mg/dl) by the gamma globulin fraction (%). The association between gamma globulin levels and oncological outcomes was statistically evaluated., Results: During a median follow-up period of 39 months, 99 (36.1%) patients experienced at least 1 tumor recurrence and 16 (5.8%) patients had disease progression. The median (interquartile range) gamma globulin level was 1.2 (1.0-1.3) mg/dl. Recurrence-free survival rate of patients with gamma globulin levels of ≥1.4 mg/dl was significant lower than that of patients with gamma globulin levels of <1.4 mg/dl (P < 0.01). There was no significant difference in progression-free survival between the 2 groups (P = 0.17). Multivariate analysis revealed that gamma globulin level of ≥1.4 mg/dl is significantly associated with higher recurrence rate (hazard ratio = 1.83, P < 0.01)., Conclusion: Gamma globulin level is significantly associated with tumor recurrence. Our results suggest that B cell immunity may be involved in tumor recurrence in patients with NMIBC., (Copyright © 2019. Published by Elsevier Inc.)

Background: Despite the development of early detection methods and new antiviral drugs, cytomegalovirus (CMV) infection remains a persistent and sometimes severe complication of stem cell transplantation (SCT). CMV antigenemia has become widely used for early detection of CMV infection after SCT., Procedure: We retrospectively analyzed risk factors for CMV antigenemia in pediatric patients following allogeneic SCT. We analyzed 74 pediatric patients who received allogeneic SCT at Sapporo Hokuyu Hospital between April 2007 and March 2018 and were alive over three months after SCT., Results: Of the 74 patients, 22 (29.7%) were CMV antigenemia positive. On univariate analyses, many patients with CMV antigenemia tested positive for CMV antibody before SCT (P < 0.001), and had lower gamma globulin levels before conditioning (P = 0.014). Multivariate analysis additionally confirmed that pre-SCT CMV antibody positivity (P < 0.001) and preconditioning gamma globulin levels under 655 mg/dL (P = 0.004) were independent risk factors for post-SCT CMV antigenemia., Conclusions: These results indicate the importance of assessing gamma globulin levels in pediatric patients prior to SCT., (© 2018 Wiley Periodicals, Inc.)

This study was conducted to evaluate an adjuvant, Montanide (IMS 3015), in improving the quality of Rift Valley fever (RVF) vaccine relative to the traditional adjuvant, aluminum hydroxide gel. Vaccinated sheep were evaluated using biochemical analysis, kidney function tests, liver function tests, and immunological tests. Sheep vaccinated with Montanide (IMS 3015) adjuvant showed significantly higher total protein, total globulin, and gamma globulin concentrations from the second week until the fifth month than the controls. Conversely, albumin concentration and the A/G ratio significantly decreased during this period. Kidney function and liver function tests revealed no differences among any of the groups. There was a significant increase in lymphocyte proportion and a decrease in neutrophil proportion in sheep vaccinated with the Montanide (IMS 3015) adjuvant. Lymphocyte cell proliferation was significantly different in sheep vaccinated with the Montanide (IMS 3015) adjuvant from that in controls. Neutralizing indices were significantly higher in sheep vaccinated with the Montanide (IMS 3015) adjuvant than in controls. The current study showed that sheep vaccinated with inactivated RVF virus with Montanide (IMS 3015) as an adjuvant were protected and no pathological symptoms or biochemical changes were detected. Moreover, the vaccine induced rapid onset of immunological responses with long durations unlike inactivated RVF vaccine with aluminum hydroxide gel., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Competing Interests: There are no conflicts of interest

This study reports on the real-time binding assessment between heavy metal ions and blood proteins immobilized onto nanoporous anodic alumina photonic crystals (NAA-PCs) by reflectometric interference spectroscopy (RIfS). The surface of NAA-PCs is chemically functionalized with γ-globulin (GG), transferrin (TFN), and serum albumin (HSA), the major proteins present in human blood plasma. Protein-modified NAA-PC platforms are exposed to analytical solutions of mercury ions of different concentrations. Dynamic changes in the effective optical thickness of protein-modified NAA-PCs in response to heavy metal ions are assessed in real time to evaluate the binding kinetics, affinity, and mechanism. Protein molecules undergo conformational changes upon exposure to mercury ions, with HSA exhibiting the strongest affinity. The combination of protein-modified NAA-PCs with RIfS allows real-time monitoring of protein-heavy metal ions interactions under dynamic flow conditions. This system is capable of detecting dynamic conformational changes in these proteins upon exposure to heavy metal ions. Our results provide new insights into these binding events, which could enable new methodologies to study the toxicity of heavy metal ions and other biomolecular interactions.

Lupus nephritis is an immune-complexes mediated glomerulonephritis. Vascular lesions and endothelial cell injuries are common in lupus nephritis and important for renal damage. However, the precise mechanisms by which immune complexes lead to endothelial cell injuries are still unclear. Autophagy is a conserved metabolic process and shows protective roles in many cell types and diseases. In present study, we investigated whether immune complexes could affect autophagy and participate in endothelial dysfunctions. Heat-aggregated gamma globulin (HAGG) was used to substitute immune complexes. Glomerular endothelial cells (GECs) were incubated with HAGG and autophagy-related markers were evaluated. Results showed that HAGG suppressed autophagy in GECs, through Akt/mTOR-dependent pathway. The combination of HAGG and tumor necrosis factor-alpha suppressed autophagy in GECs and further decreased cell viabilities. The suppressed effects of HAGG on GECs autophagy and viability, especially under inflammatory microenvironment, may provide new views for explaining the mechanisms of renal impairments in lupus nephritis., (Copyright © 2018. Published by Elsevier Inc.)

It is known that patients with rheumatoid arthritis (RA) have a higher risk of coronary heart disease and sudden cardiac death. Abnormalities in cardiac geometry appear to be involved in the setting of the cardiovascular risk, but it has never been specifically investigated in RA. We enrolled 44 patients with RA compared to 131 subjects without RA (normal, N): The RA aged between 18 and 70 years (mean 48.3 ± 2.1), 25 females, BMI 27.6 ± 0.9; N, of equal age (48.6 ± 1.2, n.s.), included 80 females (BMI 26.7 ± 0.2, ns). Cardiac Ultrasounds showed an increase of the diameter of the left ventricle but not in the septum with reduction of relative wall thickness (RWT) in the RA population compared to N. Relative wall thickness inversely correlates with biochemical parameters of inflammatory response (gamma globulin, p < 0.03; F = 5,660) and anti citrullinated peptides antibody (anti-CCP Ab) (p < 0.02; F = 7,1620) We conclude that unfavorable cardiac remodeling can increase cardiovascular risk in patients with RA.

Aleutian mink disease (AD) is a chronic viral infection that causes autoimmune disorders in minks and presents a significant economic burden on mink farming. Despite the substantial challenges presented by AD, no effective vaccine is available and only partial protection has been achieved. We constructed a whole-gene nucleic acid vaccine from an isolated virulent Aleutian mink disease virus (ADV) strain (pcDNA3.1-ADV). Based on this whole-gene nucleic acid vaccine, we generated truncated mutant constructs by removing portions of the ADV VP2 gene using overlap extension polymerase chain reaction. pcDNA3.1-ADV-428 lacks nucleotides encoding VP2 amino acid residues 428-466, and pcDNA3.1-ADV-428-487 harbors additional deletion of nucleotides coding for VP2 amino acid residues 487-501. We also generated nucleic acid vaccines for the ADV NS1 gene, truncated ADV NS1 gene, ADV VS2 gene, and truncated ADV VS2 gene: pcDNA3.1-NS1, pcDNA3.1-NS1-D, pcDNA3.1-VP2, and pcDNA3.1-VP2-D, respectively. The immunogenicity of the seven DNA vaccines was confirmed by immunofluorescent evaluation. Sixty female minks were divided into 10 groups: seven groups were immunized with the DNA vaccines, one control group was injected with phosphate-buffered saline, one group was immunized with pcDNA3.1 empty vector, and one group was immunized with inactivated ADV-G virus. ADV antibody levels, percentage of CD8 + cells in blood, and levels of γ-globulin and circulating immune complexes in the serum were evaluated longitudinally over 36 weeks after ADV challenge. Minks that were immunized with the pcDNA3.1-ADV-428-487 nucleic acid vaccine produced ADV antibodies. After ADV challenge, the minks immunized with pcDNA3.1-ADV-428-487 nucleic acid vaccine had lower γ-globulin content and lower CIC in serum compared to other immunization groups. Although the pcDNA3.1-ADV-428-487 nucleic acid vaccine did not demonstrate complete protection against ADV, it demonstrated marked efficacy and could potentially be used as a vaccine to prevent losses in mink populations due to ADV. Discovery of effective means to vaccinate mink against ADV will not only improve overall health of mink populations but will also reduce the economic impact of ADV.

It was demonstrated that low-intensity radiation of helium-neon (He-Ne) laser at 632.8nm, which leads to the transition of oxygen to a singlet state, causes the formation of reactive oxygen species (ROS) - hydrogen peroxide, hydroxyl and superoxide (hydroperoxide) radicals - in aqueous solutions. The oxygen effect - dependence of hydrogen peroxide formation on the concentration of molecular oxygen - was shown, and the participation of singlet oxygen, hydroxyl radicals and superoxide (hydroperoxide) radicals in this process was testified. Laser radiation-induced ROS in solutions of blood serum proteins, bovine serum albumin and bovine gamma-globulin, cause the formation of long-lived reactive protein species (LRPS) with a half-life of about 4h. The generation of LRPS caused by laser irradiation results in prolonged several-hour generation of ROS - hydrogen peroxide, hydroxyl and superoxide radicals. As affected by LRPS, coupled radical reactions lead to conversion of dissolved molecular oxygen to hydrogen peroxide. Irradiation with light sources away from the oxygen absorption band is not attended by formation of ROS and LRPS. A consideration is provided for the possible molecular mechanisms of ROS formation under the influence of He-Ne laser irradiation, the role of proteins in their generation and the biological significance of these processes., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objectives: To evaluate the levels of the serum gamma globulin fraction in proteinograms as a biomarker to assess the severity, and to predict the mortality and new exacerbations in patients admitted for an exacerbation of a COPD., Patients and Methods: The VIRAE study was carried out on a cohort of patients hospitalized for an exacerbation of probable infectious origin of COPD over a period of 2 years. The levels of the serum gamma globulin fraction were analyzed in the proteinogram of 120 patients. The main clinical indicators of severity were also evaluated. Key features were compared in 2 groups (gamma fraction in the proteinogram greater or less than 6.6g/dl)., Results: The levels of the serum gamma fraction in the proteinogram correlated with the FEV 1 (P=.009), the CRP (P=.04), and the number of readmissions after 6 months of hospitalization (P=.04). We observed a good association with the GOLD scale, the BODE index and the mMRC dyspnea scale; and also with treatment with oral corticoids and home oxygen therapy. We did not find it to be a good predictor of mortality, despite observing increased mortality rates one year after hospital admission in patients with low levels of the factor., Conclusions: The levels of the gamma globulin fraction in proteinograms has a good correlation with the FEV 1 . In addition, they are associated with a greater severity of patients with COPD. This simple biomarker may be useful in identifying high-risk patients., (Copyright © 2017 Elsevier España, S.L.U. All rights reserved.)

Aims: Sickle retinopathy (SR) is a major cause of blindness in sickle cell disease (SCD). The genetic mutation responsible for SCD is known, however; oxidative stress and inflammation also figure prominently in the development and progression of pathology. Development of therapies for SR is hampered by the lack of (a) animal models that accurately recapitulate human SR and (b) strategies for noninvasive yet effective retinal drug delivery. This study addressed both issues by validating the Townes humanized SCD mouse as a model of SR and demonstrating the efficacy of oral administration of the antioxidant fumaric acid ester monomethyl fumarate (MMF) in the disease., Results: In vivo ophthalmic imaging, electroretinography, and postmortem histological RNA and protein analyses were used to monitor retinal health and function in normal (HbAA) and sickle (HbSS) hemoglobin-producing mice over a one-year period and in additional HbAA and HbSS mice treated with MMF (15 mg/ml) for 5 months. Functional and morphological abnormalities and molecular hallmarks of oxidative stress/inflammation were evident early in HbSS retinas and increased in number and severity with age. Treatment with MMF, a known inducer of Nrf2, induced γ-globin expression and fetal hemoglobin production, improved hematological profiles, and ameliorated SR-related pathology. Innovation and Conclusion: United States Food and Drug Administration-approved formulations in which MMF is the primary bioactive ingredient are currently available to treat multiple sclerosis; such drugs may be effective for treatment of ocular and systemic complications of SCD, and given the pleiotropic effects, other nonsickle-related diseases in which oxidative stress, inflammation, and retinal vascular pathology figure prominently. Antioxid. Redox Signal. 25, 921-935., Competing Interests: Author Disclosure Statement V.G. and P.M.M. are coinventors of US20140171504 A1 patent titled “Methods of treating SCD and related disorders using fumaric acid esters.” The remaining authors have no disclosures or competing financial interests to report.

Silent information regulator type-1 (SIRT1) is the best-studied member of the Sirtuin (Sir2) family of nicotinamide dinucleotide (NAD)-dependent class III histone deacetylases (HDACs). Rrecently, it is suggested that SIRT1 may be involved in the development of malignant tumors including mouse lymphoma, but has not yet been explored in Angioimmunoblastic T-cell lymphoma (AITL). Therefore, we investigated the prevalence and the prognostic impact of SIRT1 expression in AITL. Immunohistochemical expression of SIRT1, p53 were evaluated by using a 2 mm core from 45 AITL patients. Positive expression of SIRT1 was seen in 71.11% (32 of 45) of patients and p53 expression were seen in 53.33% (24 of 45). SIRT1 and p53 expression were significantly associated with shorter PFS by univariate analysis (P=0.009 and P < 0.001, respectively), multivariate analysis also shows that SIRT1 expression relate to worse prognosis. We also suggest inferior survival in AITL with the combined expression of SIRT1 and clinical characteristics of high IPI scores, high clinical stage, increased serum LDH, decreased HGB and increased γ-Globulin. In conclusion, our results indicate that SIRT1 is strongly expressed in AITL and it act as a clinically significant prognostic indicator for AITL patients, may also serve as a therapeutic target in AITL.

We report the development of thermoresponsive 4-mercaptoethylpyridine (MEP)-based chromatographic microsphere based resins for antibody separation that show switchable release abilities by adsorbing immunoglobulins at 40 °C and releasing the proteins at 5 °C. The thermoswitchable release properties were introduced to the porous resins by the grafting of linear poly(N-isopropylacrylamide) (PNIPAM) chains synthesized via reversible addition-fragmentation chain transfer (RAFT) polymerization, which were modified to possess MEP end functionalities. Adsorption of γ-globulins as a model antibody on the shortest PNIPAM-MEP (3 kDa) grafted microparticles display binding capacities of up to 20 g L(-1) at 40 °C and a significant decrease in binding capacity to less than 2.5 g L(-1) at 5 °C. By switching the temperature to 5 °C, the release of bound γ-globulins is shown to be as high as 90%. The effects of polymer chain length on the binding capacity are studied in detail and found to be critical as they influence the density of MEP functionalities on the particle surfaces.

The downstream processing of therapeutic proteins is a challenging task. Key information needed to estimate applicable workup strategies (e.g. crystallization) are the interactions of the proteins with other components in solution. This information can be deduced from the second osmotic virial coefficient B22 , measurable by static light scattering. Thermodynamic models are very valuable for predicting B22 data for different process conditions and thus decrease the experimental effort. Available B22 models consider aqueous salt solutions but fail for the prediction of B22 if an additional polymer is present in solution. This is due to the fact that depending on the polymer concentration protein-protein interactions are not rectified as assumed within these models. In this work, we developed an extension of the xDLVO model to predict B22 data of proteins in aqueous polymer-salt solutions. To show the broad applicability of the model, lysozyme, γ-globulin and D-xylose ketol isomerase in aqueous salt solution containing polyethylene glycol were considered. For all proteins considered, the modified xDLVO model was able to predict the experimentally observed non-monotonical course in B22 data with high accuracy. When used in an early stage in process development, the model will contribute to an efficient and cost effective downstream processing development., (Copyright © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Biocompatibility of nanoparticles depends on their binding behavior with biomolecules. Herein, we have reported the interaction of three different biological macromolecules such as hemoglobin, gamma globulin and transferrin with hydroxyl group functionalized Multi-Walled Carbon Nanotubes (OH-MWCNTs). Multiple spectroscopic methods were utilized to identify the binding cum structural changes in biomolecules upon their interaction. Hyperchromic effect observed in the UV-visible spectra, and the quenching behavior from fluorescence emission evidences the existence of bio-nanotube complex formation. Synchronous and three-dimensional fluorescence spectra of biomolecules, in correspondence with Trp and Tyr residues showed the possible disturbance towards their aromatic micro-environment. Changes observed in the FTIR and FT-Raman amide bands, and amino acid residue position of biomolecules upon interaction with CNTs showed the possible effect towards their secondary structure. Further studies with CD spectroscopy indicated the loss of alpha-helical structures quantitatively. The study remains significant in evaluating the biosafety profile of functionalized MWCNTs for their in vivo biomedical applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specific Ift88 knock-out mouse line (K5rtTA;tetOCre;Ift88(fl/fl)) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation., Significance Statement: We show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory neurons and may include alterations in OE maintenance and regeneration., (Copyright © 2015 the authors 0270-6474/15/3513761-12$15.00/0.)

Objectives: Hepatitis A virus (HAV) infection tends to be a self-limiting disease without serious sequelae, but fulminant hepatitis, with a high mortality, develops in 0.1-0.2% of the cases. Sometimes, HAV infection precipitates autoimmune hepatitis (AIH). We aimed to assess the frequency and clinical significance of serologic markers of autoimmunity during hepatitis A infection with an acute or fulminant presentation compared with those in AIH., Methods: The study included 126 children: 46 with HAV infection (33 with acute and 13 with fulminant presentation), 53 with AIH, and 27 healthy controls. In all, we measured autoantibodies titer (antinuclear antibody, antismooth muscle antibody, and liver kidney microsomal antibody-1) and serum gammaglobulins., Results: Autoantibodies were detected in the majority of HAV (63.1%) and AIH (79.2%) groups, but in none of the controls. Gammaglobulins were significantly higher in the HAV group (1.93±0.57 g/dl) than in the controls (1.32±0.29 g/dl), but lower than that in the AIH group (2.93±1.2 g/dl) (P<0.0001 for all). In the HAV group, gammaglobulins were significantly higher in those with fulminant (2.21±0.46 g/dl) than in those with acute presentation (1.82±0.57 g/dl) (P=0.019), but comparable with that in AIH (P=0.095). Gammaglobulins correlated significantly with disease severity in both HAV and AIH groups., Conclusion: Hypergammaglobulinemia and a high occurrence of autoantibodies are encountered in HAV infection. This may support the immunological basis of its pathogenesis. Moreover, the higher gammaglobulins in fulminant HAV, with an insignificant difference from that in AIH, suggest that a more aggressive immunological reaction is related to this presentation.

Objective: To assess the diagnostic value of salivary gland ultrasonography (SGUS) for primary SS (pSS) and to compare the usefulness of two existing SGUS scoring systems., Methods: Ultrasonography examination of major salivary glands was conducted for 105 pSS patients and 41 disease control subjects without SS and 16 healthy control subjects. The imaging features were graded using two different scoring systems (0-16 and 0-48, respectively) obtained from the grades of bilateral parotid and submandibular glands. Receiver operating characteristic curves were used to describe and compare the diagnostic accuracy of the two ultrasonography echostructure scoring systems for pSS. The agreement of diagnosis for pSS between the two scoring systems was determined by κ-statistics., Results: SGUS scores for the pSS group were significantly higher than those for the non-pSS group (P < 0.001). The best score cut-off was 7 in the 0-16 system (80% sensitivity and 93% specificity, respectively), and it was 15 in the 0-48 system (88.6% sensitivity and 84.2% specificity, respectively). Compared with the 0-16 system, combined evaluation of all four glands when using the 0-48 system improved the diagnostic accuracy. Association analysis of both scoring systems showed a positive correlation of SGUS scores with RF and γ-globulin% (P < 0.05, overall)., Conclusion: SGUS is a feasible method for pSS diagnosis with higher sensitivity using the 0-48 system and better specificity using the 0-16 system. SGUS scores are related to RF and γ-globulin%., (© The Author 2015. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)

Cryogel monoliths with interconnected macropores (10-100μm) and hydrophilic surfaces can be employed as chromatography media for protein retention in steric exclusion chromatography (SXC). SXC is based on the principle that the exclusion of polyethylene glycol (PEG) on both a hydrophilic chromatography surface and a protein favors their association, leading to the protein retention on the chromatography surface. Elution of the retained protein can be achieved by reducing PEG concentration. In this work, the surface of polyacrylamide-based cryogel monolith was modified by grafting zwitterionic poly(carboxybetaine methacrylate) (pCBMA), leading the increase in the surface hydrophilicity. Observation by scanning electron microscopy revealed the presence of the grafted pCBMA chain clusters on the cryogel surface, but pCBMA grafting did not result in the changes of the physical properties of the monolith column, and the columns maintained good recyclability in SXC. The effect of the surface grafting on the SXC behavior of γ-globulin was investigated in a wide flow rate range (0.6-12cm/min). It was found that the dynamic retention capacity increased 1.4-1.8 times by the zwitterionic polymer grafting in the flow rate range of 1.5-12cm/min. The mechanism of enhanced protein retention on the zwitterionic polymer-grafted surface was proposed. The research proved that zwitterionic polymer modification was promising for the development of new materials for SXC applications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Various assays have been used as an aid to diagnose failure of passive transfer (FPT) of immunoglobulins in neonatal foals, but often lack sensitivity as screening tests, or are time consuming to perform and impractical as confirmatory tests. The aim of the present study was to evaluate whether measurement of serum total globulins (TG; i.e. total protein minus albumin) can be used to estimate the electrophoretic gamma globulin (EGG) fraction in hospitalised neonatal foals with suspected FPT. Sample data from 56 foals were evaluated retrospectively. The coefficient of rank correlation was 0.84. The area under the curve of ROC analysis was 0.887, 0.922 and 0.930 for EGG concentrations <2 g/L, < 4 g/L and <8 g/L, respectively. Cut-offs for TG achieved ≥90% sensitivity for detecting EGG <2 g/L, < 4 g/L and <8 g/L, with negative predictive values of >97% and >94%, using prevalence of 15% and 30%, respectively. These results suggest that measurement of TG can be used as a guide to predicting EGG, provided that appropriate cut-off values are selected, and this technique could be a useful initial screening test for FPT in foals., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

A randomized, double-blind, placebo controlled trial of a single dose of 200,000 I.U. of vitamin A with daily zinc supplementation was conducted with children in Mojo village, Surabaya City. Children aged 48 to 60 months were randomized to receive a single dose of 200,000 I.U. of vitamin A plus zinc sulfate (n=12) or a single dose of 200,000 I.U. of vitamin A (n=12) plus placebo six days a week for six months. Children were evaluated weekly for nutrient intake and for IGF-1, C-reactive protein levels, gamma globulin levels, serum zinc, serum retinol, bone age and the index height for age at six months. At the end of the study, there was a significant increase in the serum retinol level (p<0.03), serum zinc level (p<0.03), IGF-1 hormone (p<0.04) and Z-score height for age (p<0.001), bone age (p<0.01), and gamma globulin level (p<0.04) and a significant decrease in the amount of infection/inflammation measured by CRP level (p<0.001). There was also a significant correlation between CRP level and height for age (p<0.01), and between gamma level and height for age (p<0.01). These results suggest that combined vitamin A and zinc supplementation reduces the risk of infection and increases linear growth among children, and thus may play a key role in controlling infection and stunted growth for children under five years old., (Copyright © 2014 Elsevier GmbH. All rights reserved.)

Objective: The aims of this study were to describe the clinical presentation of primary SS (pSS) in a large cohort of patients by assessing the prevalence of the patient subgroups at high risk for severe extraglandular manifestations and to explore the influence of the patients' serological profile on disease severity and on immunosuppressive drug utilization., Methods: Cumulative demographic, clinical, serological, histological and therapeutic data of 1115 pSS patients were retrospectively evaluated. Independent serological markers for glandular and extraglandular disease manifestations were identified by logistic regression., Results: The cohort included 1115 (1067 female, 48 male) pSS patients. Severe extraglandular manifestations were detectable in 15% of the patients and were represented by active synovitis (11%), axonal sensory-motor neuropathy (2%), severe leucocytopenia (14%), cutaneous vasculitis (6%) and non-Hodgkin's lymphoma (4.5%). We found that low C3/C4, hypergammaglobulinaemia, RF and cryoglobulinaemia were markers of severity for pSS. According to the number of serological variables, the patients were subdivided into three distinct groups: favourable (no serological markers), intermediate (one serological marker) and poor (two or more serological markers). In comparison with the other two patient groups, pSS patients presenting with two or more adverse determinants had a higher frequency of severe visceral disease complications and required more aggressive therapeutic interventions., Conclusion: This study confirmed that the prevalence of the pSS high-risk subset for severe systemic manifestations is ∼15%. Serological markers might help in the early identification of patients who are candidates to receive more aggressive treatments.

It has been previously established that heat induces the formation of reactive oxygen species (ROS) in aqueous solutions. In biological systems, ROS cause oxidative damage predominantly to proteins due to their abundance and sensitivity to oxidation. Proteins oxidized by the action of X-rays represent long-lived reactive species, which trigger the secondary generation of ROS (Bruskov et al. (2012) [25]). Here we studied the possibility of formation of long-lived species of the blood serum proteins bovine serum albumin and bovine gamma-globulin in air-saturated solutions under the action of heat. It is shown that heat induces the generation of long-lived protein species, which in turn generate ROS ((1)О2, (·)O2(-), (·)OН, and H2O2). The formation of the long-lived reactive species of BSA and BGG with a half-life of about 4h induced by moderate hyperthermia was revealed using the chemiluminescence of protein solutions. It was found that long-lived reactive species of BSA and BGG cause prolonged generation of H2O2. The results obtained suggest that H2O2 produced by proteins after heating represents a messenger in signaling pathways and produces therapeutic effects in living organisms., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Autonomous self-propelled catalytic microjets are envisaged as an important technology in biomedical applications, including drug delivery, micro/nanosurgery, and active dynamic bioassays. The direct in vivo application of these microjets, specifically in blood, is however impeded by insufficient knowledge on the in vivo viability of the technique. This study highlights the effect of blood proteins on the viability of the microjets. The presence of blood proteins, including serum albumin and γ-globulins at physiological concentrations, has been found to dramatically reduce the viability of the microjets. The reduction of viability has been measured in terms of a lower number of active microjets and a decrease in the velocity of propulsion. It is clear from this study that in order for microjets to function in biomedical applications, different modes of propulsion besides platinum-catalyzed oxygen bubble ejection must be employed. These findings have serious implications for the biomedical applications of catalytic microjets., (Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Background: Overlap syndrome of autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC) is considered when the patient presents with the diagnostic criteria of both diseases at some stage of the medical history, either simultaneously or consecutively., Aim: To report on a new case of overlap syndrome and describe the clinical presentation, progression, radiological studies, histological characteristics, and therapeutic options of this rare association., Case Report: A 10-year-old boy presented with jaundice and hepatosplenomegaly. Levels of plasma aminotransferases, gamma-glutamyl transferase, serum alkaline phosphatase and gammaglobulins were elevated. Anti-liver cytosol and perinuclear antineutrophilic cytoplasmic antibodies were positive. Liver biopsy showed features of interface hepatitis with ductopenia. Magnetic resonance cholangiography revealed bile duct stenosis and dilations. Serological findings associated with radiological and histological features confirmed the diagnosis of overlap syndrome of AIH with PSC. Treatment with prednisone, azathioprine, and ursodeoxycholic acid led to a good response., Conclusion: The possibility of AIH-PSC overlap syndrome should be considered in all children with AIH and, with clinical, biochemical, or histological signs of PSC, complementary investigations should be done to confirm the diagnosis so as to urgently initiate appropriate treatment with immunosuppressive medication and ursodeoxycholic acid., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Avian tuberculosis is an important disease affecting all species of birds and is most often caused by Mycobacterium avium or Mycobacterium genavense. Blood proteins are important diagnostic constituents in gastrointestinal, hepatic, renal, and infectious diseases., Objective: The aim of the study was to compare serum protein profiles of domestic pigeons (Columba livia var. domestica) infected with Mycobacterium avium subsp. avium (MAA), with healthy pigeons., Methods: Serum samples were collected from 80 pigeons with clinical signs of tuberculosis, all kept in the same loft. All birds were necropsied and cultured for mycobacteriosis; positive cultures were typed for MAA by PCR reactions targeting 16S rRNA, IS901 and IS1245. The concentration of total serum proteins was determined by the biuret method and spectrophotometry. Individual protein fractions were analyzed by cellulose acetate electrophoresis and extrapolated based on total protein concentration. For statistical analysis, the infected birds were compared with healthy pigeons., Results: A total of 37 pigeons with culture results positive for MAA were selected and allocated to 2 groups, a culture-positive group with macroscopic lesions of tuberculosis and another without macroscopic lesions. Six protein fractions were identified: prealbumin, albumin, alpha-1, alpha-2, and beta globulins and gamma globulins. Concentrations of total protein, beta globulins and gamma globulins were statistically significantly higher in the infected pigeons when compared with the control group. There were no significant differences between the groups of birds with or without macroscopic lesions., Conclusions: Statistically significant differences in total protein, and beta and gamma globulin concentrations in all infected pigeons suggest that serum protein electrophoresis represents a nonspecific but valuable indicator for tuberculosis in pigeons., (© 2013 American Society for Veterinary Clinical Pathology.)

As a model for understanding how molecular crowding influences diffusion and transport of proteins in cellular environments, we combined experimental and theoretical approaches to study the diffusion of proteins in highly concentrated protein solutions. Bovine serum albumin and γ-Globulin were chosen as molecular crowders and as tracers. These two proteins are representatives of the main types of plasma protein and have different shapes and sizes. Solutions consisting of one or both proteins were studied. The self-diffusion coefficients of the fluorescently labeled tracer proteins were measured by means of fluorescence correlation spectroscopy at a total protein concentration of up to 400 g/L. γ-Globulin is found to have a stronger influence as a crowder on the tracer self-diffusion coefficient than Bovine serum albumin. Brownian dynamics simulations show that the excluded volume and the shape of the crowding protein have a significantly stronger influence on translational and rotational diffusion coefficients, as well as transient oligomerization, than hydrodynamic or direct interactions. Anomalous subdiffusion, which is not observed at the experimental fluorescence correlation spectroscopy timescales (>100 μs), appears only at very short timescales (<1 μs) in the simulations due to steric effects of the proteins. We envision that the combined experimental and computational approach employed here can be developed to unravel the different biophysical contributions to protein motion and interaction in cellular environments by systematically varying protein properties such as molecular weight, size, shape, and electrostatic interactions., (Copyright © 2013 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study is to estimate whether the occupational exposure to low dose of anaesthetic gases could cause alterations of haematochemical hepatic and renal parameters in the health workers of a city hospital., Materials and Methods: After excluding the main confounding factors, 154 exposed subjects and 98 not exposed controls were included in the study. The exposed subjects were divided in more exposed (group 1: n.54) and less exposed (group 2: n.100). Each worker included in this study underwent the CBC test (Complete Blood Count test). The differences between means were compared using the Student T test for unpaired data and considered significant when the p value was < 0.05., Results: The mean values of serum albumin, alpha 1, alpha 2, beta and gamma globulins were significantly decreased in health workers of both groups compared to controls. The mean values of serum creatinine and gamma-GT were significantly higher in health workers of group 2 compared to controls., Conclusions: The obtained results suggest that occupational exposure to low dose of anaesthetic gases could influence haematochemical hepatic and renal parameters in exposed health workers.

This study was planned to determine the effects of lycopene treatment on serum protein fractions in experimental diabetic rats. In order to induce diabetes in rats in the diabetes (D) and diabetes + lycopene (DL) groups, rats were given 45 mg/kg single-dose streptozotocin intraperitoneally. Lycopene (10 mg/kg/day dissolved in sunflower oil) was administered to the rats in the lycopene-only (L) and DL groups. Blood glucose levels and HbA1c% in DL group and diabetes group increased (p < 0.05) compared to control and L group. Total protein, albumin, α1, α2, and β globulin fractions of diabetic and DL groups were lower than control and L groups (p < 0.05). D group had lowest gamma (γ) globulin levels among other groups (p < 0.05). The γ globulin levels was slightly increased than diabetic groups (D and DL), but it was still lower than control and L groups (p < 0.05). The highest value of A/G ratio was observed in diabetic group. Similarly, the % level of A/G ratio of D group was higher than other groups. It was noted that the A/G ratio decreased and reached to control group levels after lycopene treatment.

Plasma γ-globulin fraction proteins, copper and zinc cations, and metal complexes formed by them with human serum γ-globulin induce the production of early (24-h incubation) IL-1β by human blood cells. The protein modified by Zn cations 1.2 times more actively (p<0.01) induced early IL-1β than the control γ-globulin, while γ-globulin metal complex with copper was 1.4 times less active (p<0.1) than the control protein. The regularities of induction changed over the course of 48-h incubation: zinc cations chelated by γ-globulin fraction protein reduced, while copper cations stimulated the realization of the protein induction potential in the metal complex.

Serum protein electrophoresis is widely used in clinical laboratories to measure the relative abundance of each obtained fraction. Moreover, we found that the migration time of the γ-globulin fraction can be reproducibly determined (CV = 1.1%). Immunoglobulins were purified from serum using protein L-agarose and their N-glycosylation was studied using CE on a DNA sequencer. Liver fibrosis patients showed a lower level of sialylation and this moderately correlates with the migration time of the γ-globulins (r = 0.2-0.4). This allowed us to differentiate healthy individuals from these patients with an acceptable diagnostic accuracy (area under the curve = 0.75). This glycomics approach could become a significant added value to a daily, routine clinical test.