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BackgroundRecombinant human immunoglobulin M22 (rHIgM22) has promoted remyelination in animal models and was well tolerated in people with clinically stable multiple sclerosis.ObjectiveSafety/tolerability of a single rHIgM22 dose was investigated following an acute relapse and to determine whether this enhanced CNS/CSF concentrations.MethodsAdults (N = 27) with acute relapse were assigned to rHIgM22 (0.5 or 2.0 mg/kg) or placebo. Study included screening/steroid administration periods and 10 study visits over 6 months. rHIgM22 CSF concentrations were assessed on days 2 and 29. Pharmacokinetic and safety samples were taken for up to 60 days. Assessments included adverse events and other clinical measures. Brain magnetic resonance imaging was performed with/without gadolinium.ResultsrHIgM22 CSF levels were consistent with dose-dependent concentration on both days 2 and 29. Infusion was generally well tolerated during an acute relapse. Immunogenicity was mild. Most adverse events did not appear to be dose dependent, were mild/moderate, and were events often associated with multiple sclerosis.ConclusionAlthough limited by high variability and small sample size, the data suggest enhanced CNS uptake associated with a drop in CSF levels. This study demonstrated safety of an antibody directed to myelin and oligodendrocytes in the course of active demyelinating disease. Further research into rHIgM22 is warranted.ClinicalTrials.gov: NCT02398461 https://clinicaltrials.gov/ct2/show/study/NCT02398461?term=M22&draw=2&rank=8.

In a one-step process, nanoscale magnetite was modified with 3-aminopropyltriethoxysilane to introduce amino groups onto its surface. The resulting nanocomposite exhibited a particle size of approximately 13.6 nm, with agglomerates measuring 150 nm in size. The nanoparticles were densely packed, creating gaps (pores) between them of up to 13 nm and a specific surface area of 114 m2⋅g−1. The nanocomposite possessed approximately 0.8 mmol⋅g−1 of amino groups. Electrokinetic potential data confirmed the presence of basic groups, and the isoelectric point was observed at pH 10. The adsorption of human immunoglobulin in a 0.9% NaCl solution was investigated using the synthesized nanoparticles, with a maximum adsorption capacity reaching 40.5 mg⋅g−1. Infrared spectroscopy data of the Ig-loaded sample and the fitting of the adsorption isotherm using the Langmuir adsorption model indicated chemisorption of the immunoglobulin on the surface of the Fe3O4/≡Si(CH2)3NH2 particles. [ABSTRACT FROM AUTHOR]

This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines. [ABSTRACT FROM AUTHOR]

Antimicrobial resistance (AMR) is a global health problem that causes more than 1.27 million deaths annually; therefore, it is urgent to focus efforts on solving or reducing this problem. The major causes of AMR are the misuse of antibiotics and antimicrobials in agriculture, veterinary medicine, and human medicine, which favors the selection of drug-resistant microbes. One of the strategies proposed to overcome the problem of AMR is to use polyvalent human immunoglobulin or IVIG. The main advantage of this classic form of passive immunization is its capacity to enhance natural immunity mechanisms to eliminate bacteria, viruses, or fungi safely and physiologically. Experimental data suggest that, for some infections, local administration of IVIG may produce better results with a lower dose than intravenous application. This review presents evidence supporting the use of polyvalent human immunoglobulin in AMR, and the potential and challenges associated with its proposed usage.

Objectives: To compare the frequency of hospitalization in children with Inborn Errors of Immunity with antibody deficiency previous to intravenous immunoglobulin (pre- IVIG) with a one-year period after initial IVIG (post-IVIG). Methods: Medical reports of 45 patients during an eight-year period were reviewed from 2018 to 2019. Wilcoxon-test was used for related samples. Results: Forty-five children were included in the study, aged 29–249 months of age, and most of them (64.4%) were males. Median ages at onset symptoms and at diagnosis were 6 and 73 months old, respectively. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnoses (31.1% and 17.8%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Hyper IgM, transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID) were also reported, in a low frequency. Forty-four (97.8%) patients were hospitalized before IVIG, and 10 patients (22.2%) after. Annual mean hospital admission reduced from 2.5 to 0.5, pre and post-IVIG, respectively (p

This review is focused on the use of hyperimmune globulin therapy to treat some infectious diseases of viral or bacterial origin. Despite the introduction of antibiotics and vaccines, plasma immunoglobulin therapy from whole blood donation can still play a key role. These treatments provide passive transfer of high-titer antibodies that either reduces the risk or the severity of the infection and offer immediate but short-term protection against specific diseases. Antibody preparations derived from immunized human donors are commonly used for the prophylaxis and treatment of rabies, hepatitis A and B viruses, varicella-zoster virus, and pneumonia caused by respiratory syncytial virus, Clostridium tetani, Clostridium botulinum. The use of hyperimmune globulin therapy is a promising challenge, especially for the treatment of emerging viral infections for which there are no specific therapies or licensed vaccines.

The article highlights the course of long-term SARS-CoV-2 infection in a patient with a secondary immunodeficiency developed with B-cell-depleting therapy of the underlying disease. Analysis of the intrapatient virus evolution revealed an inpatient S:G75A mutation that alters the 72GTNGTKR78 motif of the S-protein, with a possible role in binding to alternative cellular receptors. Therapy with a ready-made COVID-19-globulin preparation (native human immunoglobulin G (IgG) derived from the plasma of convalescent COVID-19-patients) resulted in rapid improvement of the patient’s condition, fast, and stable elimination of the virus, and passive immunization of the patient for at least 30 days. The results suggest the use of products containing neutralizing antibodies opens new prospects for treatment algorithms for patients with persistent coronavirus infection, as well as for passive immunization schemes for patients with a presumably reduced specific response to vaccination.

Objective: To observe the curative effect of intravenous injection of human immunoglobulin combined with vancomycin in the treatment of children with sepsis, and changes in peripheral blood neutrophil-to-lymphocyte ratio (NLR) and Procalcitonin (PCT). Methods: Eighty children with sepsis admitted to the hospital from January 2011 to January 2020 were selected as the research subjects. They were divided into control group and observation group according to the random number table method, with 40 cases in each group. Children in control group were treated with vancomycin, and those in observation group were treated with intravenous injection of human immunoglobulin based on the treatment of control group. Clinical efficacy, symptom improvement time, length of hospital stay, NLR, PCT, Procalcitonin (PCT), high-sensitivity C-reactive protein (hs-CRP), White blood cell count (WBC), immune function and the incidence of adverse reactions were compared between the two groups. Results: The treatment response rate in observation group was higher than that in control group (87.50% vs. 65.00%)(P<0.05). The improvement time of nervous system symptoms, body temperature and milk refusal, and the length of hospital stay in observation group [(6.22± 1.05) d, (3.88± 0.25) d, (5.10± 0.86) d and (8.71± 2.05) d] were shorter than those in control group [(8.76± 1.53) d, (6.22± 0.64) d, (7.53± 1.46) d and (11.24± 3.36) d] (P<0.05). After treatment, peripheral blood NLR, serum PCT, hs-CRP and WBC levels in observation group [(1.35± 0.20), (0.80± 0.34) mg/mL, (3.56± 0.62) g/L and (9.12± 1.80)× 109 /L] were significantly lower than those in control group [(1.83± 0.32), (2.19± 0.73) mg/mL, ( 9. 78 ± 2. 64 ) g/L and ( 12. 26 ± 2. 59 ) × 109 /L ] (P<0. 05 ). After treatment, CD4+, CD3+ and CD4/CD8 in observation group [(42.77± 11.36)%, (41.27± 11.26)% and (1.70± 0.33)] were significantly higher than those in control group [(35.80± 9.32)%, (35.66± 9.40)% and (1.29± 0.25)](P<0.05). There was no significant difference in the incidence of adverse reactions between the two groups (10.00% vs. 7.50%) (P>0.05). Conclusion: Intravenous injection of human immunoglobulin combined with vancomycin is effective in the treatment of children with sepsis, which Can reduce inflammatory factors, and improve immune function, with high safety. [ABSTRACT FROM AUTHOR]

[Display omitted] • Four Level Lithography was employed for the design of EG-FET. • EG-FET gate layer was modified with SnS 2 and nitrogen doped graphene oxide to improve its performance. • SnS 2 /N-GO modified EG-FET was demonstrated for HIgG immunosensing. • The proposed immunosensor exhibited a LOD of 4.8 ng/mL. • The immunosensor is highly stable, selective and sensitive towards HIgG detection. Miniaturized biosensor design is widely preferred for its application in integrated platform to provide rapid and sensitive diagnosis. However, there are only few reports which employ extended gate field effect transistors (EG-FET) for immunosensing application. Herein, we designed EG-FET using four level lithography techniques. Further, the gate layer (Au/Ti) of device has been modified with Tin disulfide nanoflowers (SnS 2) and nitrogen doped graphene oxide (N-GO) hybrid composite for enhanced electrical sensing. The as-prepared SnS 2 and N-GO based nanocomposite (SnS 2 /N-GO) was characterized by various techniques. The designed SnS 2 /N-GO based EG-FET was employed as an immunosensor to detect HIgG using anti-HIgG antibody. Under optimum conditions, our miniaturized immunosensor demonstrated the detection of HIgG as low as 4.81 ng/mL. The proposed immunosensor exhibited excellent sensitivity, selectivity and reproducibility towards HIgG detection, thereby suitable for a reliable integrated biosensing platform which can detect protein concentration in real samples for clinical diagnostics. [ABSTRACT FROM AUTHOR]

Objectives: To compare the frequency of hospitalization in children with Inborn Errors of Immunity with antibody deficiency previous to intravenous immunoglobulin (pre- IVIG) with a one year period after initial IVIG (post-IVIG). Methods: Medical reports of 45 patients during an eight-year period were reviewed from 2018 to 2019. Wilcoxon-test was used for related samples. Results: Forty-five children were included in the study, aged 29-249 months of age, and most of them (64.4%) were males. Median ages at onset symptoms and at diagnosis were 6 and 73 months old, respectively. Specific antibody deficiency and unclassified hypogammaglobulinemia were the predominant diagnoses (31.1% and 17.8%, respectively). X-linked agammaglobulinemia, Hyper IgE syndrome, Hyper IgM, transient hypogammaglobulinemia of infancy, and Common Variable Immunodeficiency (CVID) were also reported, in a low frequency. Forty-four (97.8%) patients were hospitalized before IVIG, and 10 patients (22.2%) after. Annual mean hospital admission reduced from 2.5 to 0.5, pre and post-IVIG, respectively (p < 0.0001). Mean length of stay (LOS) reduced from 71 to 4.7 days/year (p < 0.0001) in general ward and in the PICU from 17.2 days/year to zero (p < 0.0002). Pneumonia was the main cause of hospital admission with a reduction in the number of episodes per patient from an average of 2.2(0.1 per year (p < 0.001). Concomitant use of antibiotic prophylaxis did not influence the number of hospital admission. Conclusion: One-year intravenous IVIG significantly decreased the number of hospitalizations and length of stay in children with impaired antibody production. Social and economic impacts would be required. [ABSTRACT FROM AUTHOR]

Neuromyelitis optica (NMO) pathogenesis involves binding of anti-aquaporin-4 (AQP4) autoantibodies (NMO-IgG) present in serum to AQP4 on astrocytes, which causes complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Human immunoglobulin G (hIgG) is effective for treatment of humorally mediated neurological autoimmune diseases and has been reported to improve disease outcome in a limited number of NMO patients. Here, we investigated hIgG actions on NMO-IgG pathogenicity using an in vivo rat model of NMO and in vitro assays. In rats administered NMO-IgG by intracerebral injection, the size of neuroinflammatory demyelinating lesions was reduced by ~50% when hIgG was administered by intraperitoneal injection to reach levels of 10-25mg/mL in rat serum, comparable with human therapeutic levels. In vitro, hIgG at 10mg/mL reduced by 90% NMO-IgG-mediated CDC following addition of NMO-IgG and human complement to AQP4-expressing cells. The hIgG effect was mainly on the classical complement pathway. hIgG at 10mg/mL also reduced by up to 90% NMO-IgG-mediated ADCC as assayed with human natural killer cells as effector cells. However, hIgG at up to 40mg/mL did not affect AQP4 cell surface expression or its supramolecular assembly in orthogonal arrays of particles, nor did it affect NMO-IgG binding to AQP4. We conclude that hIgG reduces NMO-IgG pathogenicity by inhibition of CDC and ADCC, providing a mechanistic basis to support further clinical evaluation of its therapeutic efficacy in NMO.

An all fiber-optic immunosensor based on elliptical core helical intermediate-period fiber grating (E-HIPFG) is proposed for the specific detection of human immunoglobulin G (human IgG). E-HIPFGs are all-fiber transducers that do not include any additional coating materials or fiber architectures, simplifying the fabrication process and promising the stability of the E-HIPFG biosensor. For human IgG recognition, the surface of an E-HIPFG is functionalized by goat anti-human IgG. The functionalized E-HIPFG is tested by human IgG solutions with a concentration range of 10–100 μg/mL and shows a high sensitivity of 0.018 nm/(μg/mL) and a limit of detection (LOD) of 4.7 μg/mL. Notably, the functionalized E-HIPFG biosensor is found to be insensitive to environmental disturbances, with a temperature sensitivity of 2.6 pm/°C, a strain sensitivity of 1.2 pm/με, and a torsion sensitivity of −23.566 nm/(rad/mm). The results demonstrate the considerable properties of the immunosensor, with high resistance to environmental perturbations, indicating significant potential for applications in mobile biosensors and compact devices.

Objective: To investigate the efficacy of human immunoglobulin combined with antibiotics in treating severe pediatric pneumonia., Methods: A retrospective analysis was performed on 210 pediatric patients with severe pneumonia admitted to the Department of Neonatology of Cangzhou Central Hospital from April 2019 to October 2022. Patients were divided into two groups (the observation group and the control group) based on the administration of human immunoglobulin. Clinical indexes of both groups before and after treatment were analyzed to determine the therapeutic effect of different treatment methods on pediatric severe pneumonia., Results: The durations of cough, fever, pulmonary rales, and lung shadow, and hospitalization time in the observation group were significantly shorter than those in the control group (all P<0.05). The total clinical effective rate in the observation group was significantly higher than that in the control group (P<0.05). Levels of inflammatory factors (IL-6, IL-8 and hsCRP) were decreased in both groups after treatment (all P<0.05), and were lower in the observation group compared with the control group after treatment (all P<0.05). The serum levels of IgA, IgG and IgM after five days of intervention were obviously higher than those before intervention in the observation group (all P<0.05), but the serum levels of IL-4, INF-γ and INF-γ/IL-4 were obviously lower (all P<0.05). The total incidence of adverse reactions between two groups after intervention was not statistically different (P<0.05)., Conclusion: The combination of human immunoglobulin and antibiotics for the treatment of pediatric severe pneumonia is beneficial, because it improves efficacy, boosts the immune system, and reduces inflammation., Competing Interests: None., (AJTR Copyright © 2024.)

Antibody glycosylation plays a crucial role in the humoral immune response by regulating effector functions and influencing the binding affinity to immune cell receptors. Previous studies have focused mainly on the immunoglobulin G (IgG) isotype owing to the analytical challenges associated with other isotypes. Thus, the development of a sensitive and accurate analytical platform is necessary to characterize antibody glycosylation across multiple isotypes. In this study, we have developed an analytical workflow using antibody-light-chain affinity beads to purify IgG, IgA, and IgM from 16 μL of human plasma. Dual enzymes, trypsin and Glu-C, were used during on-bead digestion to obtain enzymatic glycopeptides and protein-specific surrogate peptides. Ultra-high-performance liquid chromatography coupled with triple quadrupole mass spectrometry was used in order to determine the sensitivity and specificity. Our platform targets 95 glycopeptides across the IgG, IgA, and IgM isotypes, as well as eight surrogate peptides representing total IgG, four IgG classes, two IgA classes, and IgM. Four stable isotope-labeled internal standards were added after antibody purification to calibrate the preparation and instrumental bias during analysis. Calibration curves constructed using serially diluted plasma samples showed good curve fitting (R 2 > 0.959). The intrabatch and interbatch precision for all the targets had relative standard deviation of less than 29.6%. This method was applied to 19 human plasma samples, and the glycosylation percentages were calculated, which were comparable to those reported in the literature. The developed method is sensitive and accurate for Ig glycosylation profiling. It can be used in clinical investigations, particularly for detailed humoral immune profiling., Competing Interests: Conflict of interest The authors declare no competing interests., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Human immunoglobulin products are used for the treatment of a number of diseases, such as primary or secondary immunodeficiencies and autoimmune conditions due to the complete absence of antibodies or the production of defective immunoglobulins. Quality control of human immunoglobulin products is essential to ensure therapeutic functionality and safety. This includes testing for Fc function and anticomplementary activity (ACA), as well as verification of appropriate molecular size distribution using size-exclusion chromatography as prescribed in the European Pharmacopoeia (Ph. Eur.) monographs 0338, 0918, 2788 and 1928. To this end, specific biological reference preparations (BRPs) must be used. Stocks of the Ph. Eur. Human immunoglobulin (molecular size) BRP were running low and therefore a collaborative study was run by the European Directorate for the Quality of Medicines & HealthCare (EDQM), under the aegis of the Biological Standardisation Programme, to calibrate replacement batches. Eighteen laboratories, including manufacturers and Official Medicines Control Laboratories, took part in the study. Three batches of candidate BRPs were assessed and compared to Ph. Eur. Human immunoglobulin (molecular size) BRP 3 to ensure continuity. Based on the study results, the candidate BRPs were adopted by the Ph. Eur. Commission as Ph. Eur. Human immunoglobulin (molecular size) BRP batch 4, 5 and 6., (© Council of Europe 2024.)

Norovirus enteritis can cause intractable diarrhea in solid organ transplant (SOT) recipients, for which there are no established treatments. We reviewed medical records of 9 SOT recipients at our center who received orally administered human immunoglobulin for norovirus enteritis, and it appeared to be an effective treatment modality. [ABSTRACT FROM AUTHOR]

The article summarises materials on the certification of a candidate branch standard sample (BSS) of anti-alpha-staphylolysin content - OSO 42-28-342-2017 FSBI «SCEEMP» of the Ministry of Health of Russia, batch No. 34, production date April 1, 2017, expiry date April 1, 2018. According to the Certification programme the reaction of neutralization of staphylococcal toxin hemolytic properties was carried out to establish the range of the certified property of the candidate BSS against the WHO international standard (21±2 IU/ml). The BSS of anti-alpha-staphylolysin content can be used for quantitative determination of antibodies to staphylococcal exotoxin (alpha-staphylolysin) in the reaction of neutralization of staphylococcal toxin (alpha-toxin) hemolytic properties by specific antibodies present in human blood plasma and in a number of biologicals (normal and specific human immunoglobulins, purified and adsorbed staphylococcal toxins, and diagnostic staphylococcal toxin).

Objective : To explore the efficacy of human immunoglobulin (HIG) combined with imipenem-cilastatin sodium (IMP/CS) and piperacillin tazobactam sodium (PS/TS) in the treatment of severe pulmonary infection. Method : 99 cases patients with severe pulmonary infection who were admitted to North Hospital of Huashan Hospital Affiliated to Fudan University from March 2013 to July 2018 were selected as the study subjects. They were randomly divided into group A (33 cases, treated with HIG+IMP/CS+PS/TS), group B (33 cases, treated with IMP/CS+PS/TS) and group C (33 cases, treated with PS/TS). The effectiveness, inflammatory factors, T cell subsets and adverse reactions were observed. Result : The total clinical effective rate of group A was 96.97%, which was higher than 78.79% of group B, and that in group B was higher than 60.61% of group C (P<0.05). 7 days after treatment, the levels of C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α(TNF-α) and CD8+ in the three groups were lower than those before treatment, the CD4+ and CD4+ /CD8+ were higher than those before treatment the difference were with statistically significance (P<0.05). 7 days after treatment, the levels of CRP, IL-6, TNF-α, CD8+ in group A were lower than those in group B, and those in group B were lower than those in group C (P<0.05). 7 days after treatment, the CD4+ and CD4+ /CD8+ in group A were higher than those in group B, and those in group B were higher than those in group C (P<0.05). No adverse drug reactions occurred in the three groups during the treatment. Conclusion : HIG combined with IMP/CS and PS/TS is safe and effective in the treatment of severe pulmonary infection. It can effectively improve the inflammatory response, regulate immune function and promote the recovery of patients. [ABSTRACT FROM AUTHOR]

The safety issues of human intravenous immunoglobulin preparations are particularly important in modern pharmacotherapy for immunodeficiencies, hematologic and neurologic diseases, like as at transplant centers. Upon massive infusions of these media some complications are detected that are associated with spontaneous activation of complement system accompanied by production of anaphylatoxins, as well as activation of kallikrein/kinin, plasmin, and blood coagulation systems, changed blood rheology, initiation of intravascular hemolysis. For distinct groups of patients, these complications may be due to presence of some anti-erythrocyte antibodies (e.g., anti-A and anti-B haemagglutinins, anti-D antibodies) in the intravenous human immunoglobulin preparations. In the present review article, we show development of current quality standards for human intravenous immunoglobulins based on determination of antibody contents. Antibodies to erythrocytes represent a special safety index aiming to minimize risk of possible adverse effects connected with transfusions of human blood preparations. Different haemagglutination tests were compared to assess contents of anti-A, anti-B haemagglutinins and anti-D antibodies for specific safety of human intravenous immunoglobulins. Analysis of haemagglutination techniques for evaluation of human intravenous immunoglobulin preparations revealed their relative advantages and disadvantages. Various modifications of the methods are discussed, thus allowing to optimize process of quality control for these preparations based on detection of haemagglutinins and anti-D antibodies. We demonstrate a necessity to adjust regulations and to improve evaluation techniques for haemagglutinin determination in human immunoglobulin preparations at amounts of 100 mg/ml of protein. Special features of Russian national quality standards for human immunoglobulin preparations are considered with respect to assessment of haemagglutinins and anti-D contents. One may conclude that haemagglutination methods present the most informative and economically substantiated approach when assessing specific safety of human intravenous immunoglobulins by measuring contents of anti-A, anti-B haemagglutinins, and anti-D antibodies.

[Display omitted] • Solvothermal synthesis of bimetallic Ni/Co-Metal Organic Framework. • A highly sensitive and selective bimetallic electrochemical sensor was fabricated to detect IgG in human blood serum. • Ni/Co-MOF/NF shows excellent performance towards trace-level detection of IgG. • This Sensor reveals the lower limit of detection and dynamic linear concentration range. Electrochemical sensing is a widely used technique for the detection of biomolecules because of its low cost, high sensitivity, and versatility in terms of the various techniques that can be employed. In this study, we report a facile, cost-effective, and highly selective bimetallic Ni/Co-MOF (Nickel/Cobalt-Metal Organic Framework) on Nickel foam (NF) based electrochemical sensor for the trace-level detection of IgG (Human Immunoglobulin) antibodies in the human blood serum. In this direction, we used a simple and efficient solvothermal method to synthesize the Ni/Co-MOF, and the morphological, structural, and chemical states of the elements are studied using different material characterization techniques like TEM, FESEM, XRD, XPS, etc. The Ni/Co-MOF modified NF sensor showed a dynamic range of detection (30 fM to 10 nM) having superior sensitivity of 28 µA cm−2 mol−1 with a lower limit of detection 27.2 fM. Ni/Co-MOF/NF is highly selective over other interfering species (UA, Cl−, Ca2+, Urea, Sulphate, BSA and HAS). Real-time analysis was done using the DPV technique by the standard addition method and the sensor shows an excellent recovery percentage ̴ 97 to 98 %. Also, the addition of Ni2+ to Co enhances the electrochemical properties of a material by raising the valence of Ni2+ in Ni/Co-MOF by transferring partial electrons from Ni2+ to Co2+. The work presented here confirms Ni/Co-MOF/NF as a flexible, high-performance electrode that can be used to detect other biomolecules used in clinical diagnosis and biomedical research. [ABSTRACT FROM AUTHOR]

Candida albicans is a commensal fungus that can cause disease ranging in severity from moderate to severe mucosal infections to more serious life-threating disseminated infections in severely immunocompromised hosts. Chronic mucocutaneous candidiasis (CMC) occurs in patients with mutations in genes affecting IL-17-mediated immunity, such as STAT3, AIRE, RORC, CARD9, IL12B, and IL12RB1, or gain of function (GOF) mutations in STAT1. New strategies for the treatment of candidiasis are needed because of the increased burden of infections and the emergence of drug-resistant strains. In this study, we investigated an aspect of the role of antibodies in the control of C. albicans infection. We tested in vitro the effects of C. albicans opsonization with commercial human polyvalent intravenous IgG (IV IgG) on NADPH oxidase activity and killing of the fungi by blood leukocytes from 11 healthy donors and found a significant enhancement in both phenomena that was improved by IV IgG opsonization. Then, we hypothesized that the opsonization of Candida in vivo could help its elimination by mucosal phagocytes in human patients with mucocutaneous candidiasis. We tested a novel adjunctive treatment for oral candidiasis in humans based on topical treatment with IV IgG. For this purpose, we choose two pediatric patients with well-characterized primary immunodeficiencies who are susceptible to CMC. Two 8-year-old female patients with an autosomal recessive mutation in the IL12RB1 gene (P1, with oral candidiasis) and a GOF mutation in STAT1 (P2, with severe CMC persistent since the age of 8 months and resistant to pharmacological treatments) were treated with IV IgG administered daily three times a day as a mouthwash over the course of 2 weeks. The treatment with the IV IgG mouthwash reduced C. albicans mouth infection by 98 and 70% in P1 and P2, respectively, after 13 days, and complete fungal clearance was observed after complementary nystatin and caspofungin treatments, respectively. Therefore, treatment of oral candidiasis with human polyvalent IgG administered as a mouthwash helps eliminate mucosal infection in humans, circumventing drug resistance, and opening its potential use in patients with primary or transient immunodeficiency.

Background: Cholangitis is the most common complication after the Kasai procedure. It can be life-threatening and may affect long- and short-term outcomes of children with biliary atresia. We summarize our experiences in the prevention of early-onset cholangitis.Patients and Methods: From January 2002 to March 2013, children with biliary atresia (BA) who underwent the Kasai procedure in the General Surgical Department were included in a retrospective cohort study. These patients were divided into group A (therapy 1) and group B (therapy 2) depending on the infection prevention protocol and occurrences of cholangitis within the six months after surgery were recorded. Two hundred eighteen children were included in this cohort study. Seventy-six children (35 females and 41 males) were included in group A. One hundred forty-two children (65 females and 77 males) were included in group B. Therapy 1 was our primary protocol and included a third-generation cephalosporin, metronidazole, and human immunoglobulin. Therapy 2 was a modification of therapy 1 that involved imipenem-cilastatin and human immunoglobulin. Statistical analyses were performed. A p value below 0.05 was regarded as significant.Results: In group A, 45 children developed cholangitis within the six months after the Kasai procedure. In group B, 14 of these children experienced post-operative cholangitis. A χ2 analysis was used to examine the difference in the incidence of cholangitis between groups A and B. There was a substantial difference in the morbidity of post-operative cholangitis between groups A and B (59.2% vs. 9.9%, p = 0.000).Conclusion: Cholangitis in the early period after a Kasai procedure can be prevented effectively with an advanced prophylactic protocol. [ABSTRACT FROM AUTHOR]

Introduction: Pemphigus Vulgaris is an autoimmune disease that leads to the formation of local or generalized blisters as a result of autoantibodies against epidermal structures. Therapy with human immunoglobulin as an adjuvant is an excellent option for cases where there is resistance to usual treatment, in addition to being able to reduce the time of treatment with immunosuppressant. Thus, it is an alternative treatment for patients with severe infections or immunological deficiencies. Aim: to describe a case report about a carrier patient of pemphigus vulgaris treated with human immunoglobulin as adjuvant to oral corticosteroids. Case report: patient with 49 years old, was hospitalized in the city of Belo Horizonte (MG) presenting erosive lesions in the oral and conjunctival mucosa, with systemic worsening after starting treatment with antibiotics and anti-inflammatory. Initially, conventional steroid therapy was performed, but with no satisfactory results. Due to worsening symptoms and the diagnosis of Pemphigus Vulgaris, human immunoglobulin was included in the treatment as an adjuvant, which resulted in a progressive improvement of the patient. Conclusion: although treatment of Pemphigus Vulgaris has steroids as the first option, it is vital that the physician knows adjuvant and/or alternative therapies, such as human immunoglobulins, to assist in the treatment of patients who do not respond to steroids. [ABSTRACT FROM AUTHOR]

Commercially available, uncoated elastomeric closures were examined in regard to a potential contribution of extracted compounds from the rubber stoppers to protein aggregation under worst-case conditions. All rubber stoppers were confirmed to comply with Ph. Eur. quality requirements. Extraction with 2-propanol under reflux-conditions for 3 h led to closure-specific extraction profiles of the tested samples. One type of rubber stopper exhibited a considerably greater number and higher content of extractables. Four extracted compounds were identified as trialkyl benzene-1, 2, 4–tricarboxylates (trivial name: trimellitates), a substance class which is increasingly established as an alternative to phthalates. A highly concentrated aqueous solution of total extractables from this rubber stopper facilitated the formation of soluble and non-soluble high-molecular aggregates when incubated with model biopharmaceuticals (recombinant human immunoglobulin G (IgG) and recombinant erythropoietin (EPO)) under stress conditions (IgG: 60–64 °C for 130 min, EPO: 55 °C for 8 days). Furthermore, it was shown that the surfactant concentration (polysorbate 20, 0.1 m/v% vs. 1.0 m/v%) decisively influenced the formation of high-molecular aggregates. In case of EPO, the 10 fold increased concentration of surfactant was sufficient to prevent the aggregate formation completely. This study suggests the necessity of revisiting the current test system of Ph. Eur. monograph 3.2.9 for appropriate rubber stopper quality evaluation. [ABSTRACT FROM AUTHOR]