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Background: We conducted a systematic review to assess the safety and efficacy of Aluminum potassium sulfate and tannic acid (ALTA) sclerotherapy for the treatment of hemorrhoidal disease., Methods: Our study was conducted in accordance with the PRISMA statement (Preferred Reporting Items for Systematic Reviews and Meta-analyses) 2020. Primary endpoints included overall recurrence and type of recurrence while secondary endpoints included postoperative complications, reintervention, presence of rectal ulcer, rectal stricture, defecation abnormalities and perianal abscess. Α regression analysis, where the percentage of patients with grade II, III and IV hemorrhoidal disease was used as a covariate, was also performed., Results: Twelve studies with 4249 patients met all the inclusion criteria and were eventually included. The crude and pooled estimates of the overall recurrence and complications by the end of follow-up were 10% (95% CI, 6.52%-14.08%) and 5.20% (95% CI, 2.59%-8.52%), respectively. Regression analysis displayed no correlation between recurrence and the grade of hemorrhoid disease II, β= -0.0012 (95% CI, -0.0074 to 0.0049) ( p  = .64), grade III β= -0.0006 (95% CI, -0.0056 to 0.0045) ( p  = .79) and grade IV β = 0.0025 (95% CI, -0.0075 to 0.0124). However, a trend suggestive of increased recurrence was observed in patient populations with a higher proportion of grade IV disease., Conclusion: ALTA sclerotherapy may be a safe and viable alternative for patients with hemorrhoidal disease. Long-term follow-up and high-quality randomized controlled trials will help define the place of ALTA sclerotherapy in the armamentarium of treatment of hemorrhoids.

Objectives: Spondyloarthritis (SpA) is known as series of immune-mediated inflammatory disease of the axial and peripheral joints. Human leucocyte antigen (HLA)-B27 is a genetic risk factor for SpA. Recent evidence suggests that the interleukin -17 (IL17) axis strongly contributes to SpA. This study aimed to assess the efficacy of an IL17A peptide-based vaccine on SpA manifestations in model rats., Methods: HLA-B27/human β 2 -microglobulin (hβ 2 M) transgenic rats were immunised with heat-inactivated Mycobacterium tuberculosis (MT) to develop spondylitis and arthritis as an experimental SpA model after immunisation with a keyhole limpet hemocyanin-conjugated IL17A peptide-based vaccine with an alum adjuvant three times. The IL17A antibody titre was assessed using ELISA, and arthritis score and joint thickness were monitored two times a week. Enzyme-linked immunospot (ELISpot) assays for IL4- and interferon-γ-secreting splenocytes were conducted to evaluate IL17A-specific T cell activation. We also evaluated the effect of IL17A vaccine in SpA therapeutic model., Results: The IL17A peptide-based vaccine with alum adjuvant successfully induced antibody production and suppressed the arthritis score and joint thickness. X-ray and histological analyses showed that enthesitis, bone destruction and new bone formation were inhibited by the IL17A vaccine. The ELISpot assay showed that the IL17A peptide-based vaccine did not elicit any IL17A-reactive T cell responses. IL17A vaccine tends to mitigate, but not significant, in SpA treatment model. These data showed that the peptide-based vaccine targeting IL17A alleviated the SpA phenotype in a heat-inactivated MT-induced SpA model in HLA-B27/hβ 2 M transgenic rats., Conclusions: IL17A peptide-based vaccine may be a therapeutic option for SpA treatment., Competing Interests: Competing interests: The Department of Health Development and Medicine is an endowed department that is supported by AnGes, Daicel, and FunPep. The Department of Clinical Gene Therapy is financially supported by Novartis, AnGes, Shionogi, Boeringher, Fancl, Saisei Mirai Clinics, Rohto, and FunPep. HN is a scientific advisor of Funpep. AT, MT, SK, TE, RA, MS, HT and RM are employers and stockholders of Funpep. The funder provided support in the form of salaries for authors but did not have any additional role in the study design, data analysis, decision to publish, or preparation of this manuscript. All other authors declare no competing interests., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY. Published by BMJ.)

Background: Aluminum potassium sulfate and tannic acid sclerotherapy for hemorrhoids produced almost the same effects as excisional hemorrhoidectomy. However, its long-term effectiveness remains unknown., Objective: The purpose of this study was to investigate the long-term results of sclerotherapy using aluminum potassium sulfate and tannic acid for treating prolapsed hemorrhoids., Design: This was a retrospective review of a single-institution experience., Settings: This study was conducted within a coloproctology unit at a community-based hospital., Patients: In total, 1180 patients with grade II to IV hemorrhoids treated with injection sclerotherapy were enrolled., Main Outcome Measures: Efficacy measures included cumulative recurrence rates and postoperative complications., Results: Recurrence rates at 3, 6, and 9 years were 7.4%, 27.2%, and 47.5%. Postoperative complications included fever ≥38°C in 16 (1.4%) patients, rectal ulcer in 10 (0.9%) patients, rectal stricture in 5 (0.4%) patients, and perianal abscess in 4 (0.3%) patients., Limitations: This was a retrospective, nonrandomized, single-center study. In addition, office visits after 3 years were optional and the number of follow-ups steadily decreased., Conclusions: Sclerotherapy using aluminum potassium sulfate and tannic acid offers reasonable long-term results and is associated with low complication rates. Therefore, it seems to be an attractive alternative for patients with prolapsed hemorrhoids. See Video Abstract at http://links.lww.com/DCR/B733.RESULTADOS A LARGO PLAZO DE LA ESCLEROTERAPIA CON SULFATO DE ALUMINIO Y POTASIO, Y ÁCIDO TÁNICO PARA LAS HEMORROIDES PROLAPSADAS: ESTUDIO OBSERVACIONAL DE UN SOLO CENTRO., Antecedentes: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico para las hemorroides produjo casi los mismos efectos que la hemorroidectomía por escisión. Sin embargo, se desconoce su eficacia a largo plazo., Objetivo: El propósito de este estudio fue investigar los resultados a largo plazo de la escleroterapia con sulfato de aluminio y potasio, y ácido tánico para tratar las hemorroides prolapsadas., Diseo: Revisión retrospectiva de la experiencia de una sola institución., Entorno Clinico: Este estudio se realizó dentro de una unidad de coloproctología en un hospital comunitario., Pacientes: En total, 1.180 pacientes fueron inscritos con hemorroides grado II a IV tratados con inyecciones esclerosantes., Principales Medidas De Valoracion: Las medidas de eficacia incluyeron tasas acumulativas de recurrencia y complicaciones posoperatorias., Resultados: La tasa de recurrencia a los 3, 6 y 9 años fue del 7,4%, 27,2% y 47,5%, respectivamente. Las complicaciones posoperatorias incluyeron fiebre ≥ 38 grados Celsius en 16 pacientes (1,4%), úlcera rectal en 10 (0,9%), estenosis rectal en 5 (0,4%) y absceso perianal en 4 (0,3%) pacientes., Limitaciones: Este fue un estudio retrospectivo, no aleatorio, de un solo centro. Adicionalmente, las visitas al consultorio después de 3 años eran opcionales y el número de seguimientos disminuyó constantemente., Conclusiones: La escleroterapia con sulfato de aluminio y potasio, y ácido tánico ofrece resultados razonables a largo plazo y está asociada con bajas tasas de complicaciones. Por tanto, parece ser una alternativa atractiva para pacientes con hemorroides prolapsadas. Consulte Video Resumen en http://links.lww.com/DCR/B733. (Traducción- Dr. Francisco M. Abarca-Rendon)., (Copyright © The ASCRS 2021.)

Background: A range of safe and effective vaccines against SARS CoV 2 are needed to address the COVID 19 pandemic. We aimed to assess the safety and efficacy of the COVID-19 vaccine SCB-2019., Methods: This ongoing phase 2 and 3 double-blind, placebo-controlled trial was done in adults aged 18 years and older who were in good health or with a stable chronic health condition, at 31 sites in five countries (Belgium, Brazil, Colombia, Philippines, and South Africa). The participants were randomly assigned 1:1 using a centralised internet randomisation system to receive two 0·5 mL intramuscular doses of SCB-2019 (30 μg, adjuvanted with 1·50 mg CpG-1018 and 0·75 mg alum) or placebo (0·9% sodium chloride for injection supplied in 10 mL ampoules) 21 days apart. All study staff and participants were masked, but vaccine administrators were not. Primary endpoints were vaccine efficacy, measured by RT-PCR-confirmed COVID-19 of any severity with onset from 14 days after the second dose in baseline SARS-CoV-2 seronegative participants (the per-protocol population), and the safety and solicited local and systemic adverse events in the phase 2 subset. This study is registered on EudraCT (2020-004272-17) and ClinicalTrials.gov (NCT04672395)., Findings: 30 174 participants were enrolled from March 24, 2021, until the cutoff date of Aug 10, 2021, of whom 30 128 received their first assigned vaccine (n=15 064) or a placebo injection (n=15 064). The per-protocol population consisted of 12 355 baseline SARS-CoV-2-naive participants (6251 vaccinees and 6104 placebo recipients). Most exclusions (13 389 [44·4%]) were because of seropositivity at baseline. There were 207 confirmed per-protocol cases of COVID-19 at 14 days after the second dose, 52 vaccinees versus 155 placebo recipients, and an overall vaccine efficacy against any severity COVID-19 of 67·2% (95·72% CI 54·3-76·8), 83·7% (97·86% CI 55·9-95·4) against moderate-to-severe COVID-19, and 100% (97·86% CI 25·3-100·0) against severe COVID-19. All COVID-19 cases were due to virus variants; vaccine efficacy against any severity COVID-19 due to the three predominant variants was 78·7% (95% CI 57·3-90·4) for delta, 91·8% (44·9-99·8) for gamma, and 58·6% (13·3-81·5) for mu. No safety issues emerged in the follow-up period for the efficacy analysis (median of 82 days [IQR 63-103]). The vaccine elicited higher rates of mainly mild-to-moderate injection site pain than the placebo after the first (35·7% [287 of 803] vs 10·3% [81 of 786]) and second (26·9% [189 of 702] vs 7·4% [52 of 699]) doses, but the rates of other solicited local and systemic adverse events were similar between the groups., Interpretation: Two doses of SCB-2019 vaccine plus CpG and alum provides notable protection against the entire severity spectrum of COVID-19 caused by circulating SAR-CoV-2 viruses, including the predominating delta variant., Funding: Clover Biopharmaceuticals and the Coalition for Epidemic Preparedness Innovations., Competing Interests: Declaration of interests IS, HHH, PLi, RH, CB, BH, and JL are full-time employees of Clover Biopharmaceuticals. FR is a statistical adviser for Clover Biopharmaceuticals. RC, DA, PR, and GS are scientific advisers for Clover Biopharmaceuticals. All other authors declare no competing interests., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Typically, the killed form of microorganisms in combination with alum does not produce strong cellular immune responses. A recent investigation has indicated the role of dopamine D2 receptor antagonists like metoclopramide in reducing the polarization of immune responses toward Th2 immunity. This study was performed to evaluate the effects of a combination of alum and metoclopramide on the induction of cellular and humoral immunity in response to a heat-killed preparation ofSalmonella typhimurium(HKST). Wistar rats were immunized with the HKST vaccine alone or in combination with alum, metoclopramide, or the alum-metoclopramide mixture twice with a two-week interval. Fourteen days after the last vaccination, immune responses against S. typhimurium and the protective potential of the vaccines were assessed. The combination of alum and metoclopramide as an adjuvant augmented the potential of the HKST vaccine to enhance lymphocyte proliferation, delayed-type hypersensitivity reaction, and antibody titer. These results were concurrent with the polarization of immune response towards the Th1 response and improving protective immunity against S. typhimurium. Overall, the combination of alum and metoclopramide as an adjuvant synergistically enhanced cellular and humoral immunity after immunization with the HKST vaccine., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The study sought to formulate and evaluate suppositories using a locally produced brand of alum (Aw) obtained from bauxite waste generated at Awaso bauxite mine in the Western-North region of Ghana, for use in the treatment of hemorrhoids. The suppositories were formulated using shea butter modified, respectively, with amounts of beeswax and theobroma oil. In another development, theobroma oil was modified with different concentrations of beeswax. Drug-base interactions were investigated using attenuated total reflection-Fourier transform infrared (ATR-FTIR) spectroscopy. The suppositories were prepared using the hot melt and trituration methods. Quality control checks were carried out on the formulations. The evaluated parameters included physical characteristics (texture, presence or absence of entrapped air, and contraction holes), weight uniformity, disintegration time, drug content, and in vitro release profile of the alum from the formulated suppositories. An in vivo analysis was carried out on the most suitable formulation to ascertain its efficacy on inflamed tissues using croton oil-induced rectal inflammation in a rat model. A critical examination of the ATR-FTIR spectra revealed no drug-base interactions. The suppository formulations passed all Pharmacopoeia stated tests. The in vivo study revealed the use of suppositories ameliorated the croton oil-induced hemorrhoid in the rectoanal region of the rats., Competing Interests: The authors declare that there are no conflicts of interest regarding the publication of this article., (Copyright © 2021 Daniel A. Bartels et al.)

Abstract: Neonatal sepsis leads to significant morbidity and mortality with the highest risk of death occurring in preterm (<37 weeks) and low birth weight (<2,500 g) infants. The neonatal immune system is developmentally immature with well-described defects in innate and adaptive immune responses. Immune adjuvants used to enhance the vaccine response have emerged as potential therapeutic options, stimulating non-specific immunity and preventing sepsis mortality. Aluminum salts ("alum") have been used as immune adjuvants for over a century, but their mechanism of action remains poorly understood. This study aims to identify potential mechanisms by which pretreatment with alum induces host protective immunity to polymicrobial sepsis in neonatal mice. Utilizing genetic and cell-depletion studies, we demonstrate here that the prophylactic administration of aluminum adjuvants in neonatal mice improves sepsis survival via activation of the nucleotide oligomerization domain-like receptor family, pyrin-domain-containing 3 inflammasome and dendritic cell activation. Furthermore, this beneficial effect is dependent on myeloid, non-granulocytic Gr1-positive cells, and MyD88-signaling pathway activation. These findings suggest a promising therapeutic role for aluminum-based vaccine adjuvants to prevent development of neonatal sepsis and improve mortality in this highly vulnerable population., Competing Interests: The authors report no conflicts of interest., (Copyright © 2020 by the Shock Society.)

Enhanced type 2 helper T (Th2) cell responses to inhaled harmless allergens are strongly associated with the development of allergic diseases. Antigen formulated with an appropriate adjuvant can elicit suitable systemic immunity to protect individuals from disease. Although much has been learned about Th1-favored immunomodulation of OK-432, a streptococcal preparation with antineoplastic activity, little is known about its adjuvant effect for allergic diseases. Herein, we demonstrate that OK-432 acts as an adjuvant to favor a systemic Th1 polarization with an elevation in interferon- (IFN-) γ and ovalbumin- (OVA-) immunoglobulin (Ig) G2a. Prior vaccination with OK-432 formulated against OVA attenuated lung eosinophilic inflammation and Th2 cytokine responses that were caused by challenging with OVA through the airway. This vaccination with OK-432 augmented the ratios of IFN- γ /interleukin- (IL-) 4 cytokine and IgG2a/IgG1 antibody compared to the formulation with Th2 adjuvant aluminum hydroxide (Alum) or antigen only. The results obtained in this study lead us to propose a potential novel adjuvant for clinical use such as prophylactic vaccination for pathogens and immunotherapy in atopic diseases.

Purpose of Review: There are various specific therapeutic intervention available to treat hemorrhagic cystitis, once emergency treatment has been carried out. The lack of prospective studies, because of the relative rarity of this condition, makes it difficult to hierarchize the therapeutic sequence. The present review presents and summarizes the literature published on radiation-induced hemorrhagic cystitis from April 2015, date of a precedent exhaustive review, to March 2018., Recent Findings: During our period of interest, 13 clinical studies and two new clinical trials protocols were published. Most of the clinical studies were retrospective and presented data about hyperbaric oxygen (HBO) therapy, comforting its place as a well tolerated and effective first-line treatment. Other studies reported the outcomes of treatments with alum, formalin, silver nitrate, fulguration with laser or definitive surgery., Summary: Although authors seem to agree that formalin and surgery have their role as effective but potentially morbid last-line treatments, there is no consensus on primary approach to management of radiation-induced hemorrhagic cystitis beyond symptomatic measures. Several treatments have proven excellent response rates and few side effects. The results of on-going prospective studies on mesenchymal stromal cells or tacrolimus instillations are awaited, but the main discriminating factor to choose between treatments remains local availability.

Toxic effects of available therapeutics are major drawbacks for conventional management approaches in parasitic infections. Vaccines have provided a promising opportunity to obviate such unwanted complications. In present study, we examined immune augmenting capacities of an emerging adjuvant, Naltrexone, against Fasciola hepatica infection in BALB/c mice. Seventy BALB/c mice were divided into five experimental groups (14 mice per group) including 1- control (received PBS), 2- vaccine (immunized with F. hepatica E/S antigens), 3- Alum-vaccine (immunized with Alum adjuvant and E/S antigens), 4- NLT-vaccine (immunized with NLT adjuvant and E/S antigens), and 5- Alum-NLT-vaccine (immunized with mixed Alum-NLT adjuvant and E/S antigens). Lymphocyte stimulation index was assessed by MTT assay. Production of IFN-γ, IL-4, IgG2a and IgG1 was assessed by ELISA method. Results showed that NLT, either alone or in combination with alum, can induce immune response toward production of IFN-γ and IgG2a as representatives of Th1 immune response. Also, using this adjuvant in immunization experiment was associated with significantly high proliferative response of splenocytes/lymphocytes. Utilization of mixed Alum-NLT adjuvant revealed the highest protection rate (73.8%) in challenge test of mice infected with F. hepatica. These findings suggest the potential role of NLT as an effective adjuvant in induction of protective cellular and Th1 immune responses against fasciolosis., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Survivin has received attention as a potential target for cancer immunotherapy because of its crucial role in oncogenesis. We undertook this study to evaluate the immunotherapeutic potential of combination of recombinant survivin along with adjuvant alum and immune modulator Mycobacterium indicus pranii (MIP). In vivo efficacy of the combination was studied in an invasive murine breast cancer model. Recombinant survivin protein was purified from Escherichia coli based expression system and characterized by western blotting. Purified survivin protein was combined with alum and MIP and was used for immunization of Balb/c mice. Antigen-primed animals were then challenged with syngeneic mammary tumor cells known as 4T-1. Balb/c mice spontaneously develop tumor when inoculated with 4T-1 cells. Antigen and adjuvant combination was immunogenic and significantly suppressed tumor growth in mice immunized with combination of recombinant survivin (10 µg), alum, and MIP. This is the first report that describes a combination immunotherapy approach using recombinant survivin, alum, and MIP in highly metastatic murine breast cancer model and holds promise for development of new biotherapeutics for cancer.

The high mortality in neonatal sepsis has been related to both quantitative and qualitative differences in host protective immunity. Pretreatment strategies to prevent sepsis have received inadequate consideration, especially in the premature neonate, where outcomes from sepsis are so dismal. Aluminium salts-based adjuvants (alum) are used currently in many paediatric vaccines, but their use as an innate immune stimulant alone has not been well studied. We asked whether pretreatment with alum adjuvant alone could improve outcome and host innate immunity in neonatal mice given polymicrobial sepsis. Subcutaneous alum pretreatment improves survival to polymicrobial sepsis in both wild-type and T and B cell-deficient neonatal mice, but not in caspase-1/11 null mice. Moreover, alum increases peritoneal macrophage and neutrophil phagocytosis, and decreases bacterial colonization in the peritoneum. Bone marrow-derived neutrophils from alum-pretreated neonates produce more neutrophil extracellular traps (NETs) and exhibit increased expression of neutrophil elastase (NE) after in-vitro stimulation with phorbol esters. In addition, alum pretreatment increases bone marrow and splenic haematopoietic stem cell expansion following sepsis. Pretreatment of neonatal mice with an alum-based adjuvant can stimulate multiple innate immune cell functions and improve survival. These novel findings suggest a therapeutic pathway for the use of existing alum-based adjuvants for preventing sepsis in premature infants., (© 2017 British Society for Immunology.)

Adjuvants have been deliberately added to vaccines since the 1920's when alum was discovered to boost antibody responses, leading to better protection. The first adjuvants were discovered by accident and were used in the safer but less immunogenic subunit vaccines, supposedly by providing an antigen depot to extend antigen presentation. Since that time, much has been discovered about how these adjuvants impact cells at the tissue site to activate innate immune responses, mobilize dendritic cells and drive adaptive immunity. New approaches to vaccine construction for infectious diseases that have so far not been well addressed by conventional vaccines often attempt to induce antibodies, polyfunctional CD4 + T cells and CD8 + CTLs. The discovery of pattern recognition receptors and ligands that drive desired T cell responses has led to development of novel adjuvant strategies using immunomodulatory agents to direct appropriate immune responses., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Adjuvants are included in sub-unit or recombinant vaccines to enhance the potency of poorly immunogenic antigens. Adjuvant discovery is as complex as it is a multidiscplinary intersection of formulation science, immunology, toxicology, and biology. Adjuvants such as alum, which have been in use for the past 90 years, have illustrated that adjuvant research is a methodical process. As science advances, new analytical tools are developed which allows us to delve deeper into the various mechanisms that generates a potent immune response. Additionally, these new techniques help the field learn about our existing vaccines and what makes them safe, and effective, allowing us to leverage that in the next generation of vaccines. Our goal in this chapter is to define the concept, need, and mechanism of adjuvants in the vaccine field while describing its history, present use, and future prospects. More details on individual adjuvants and their formulation, development, mechanism, and use will be covered in depth in the next chapters.

This study introduces a flexible format for tolerogenic vaccination that incorporates IFN-β and neuroantigen (NAg) in the Alum adjuvant. Tolerogenic vaccination required all three components, IFN-β, NAg, and Alum, for inhibition of experimental autoimmune encephalomyelitis (EAE) and induction of tolerance. Vaccination with IFN-β + NAg in Alum ameliorated NAg-specific sensitization and inhibited EAE in C57BL/6 mice in pretreatment and therapeutic regimens. Tolerance induction was specific for the tolerogenic vaccine Ag PLP178-191 or myelin oligodendrocyte glycoprotein (MOG)35-55 in proteolipid protein- and MOG-induced models of EAE, respectively, and was abrogated by pretreatment with a depleting anti-CD25 mAb. IFN-β/Alum-based vaccination exhibited hallmarks of infectious tolerance, because IFN-β + OVA in Alum-specific vaccination inhibited EAE elicited by OVA + MOG in CFA but not EAE elicited by MOG in CFA. IFN-β + NAg in Alum vaccination elicited elevated numbers and percentages of FOXP3 + T cells in blood and secondary lymphoid organs in 2D2 MOG-specific transgenic mice, and repeated boosters facilitated generation of activated CD44 high CD25 + regulatory T cell (Treg) populations. IFN-β and MOG35-55 elicited suppressive FOXP3 + Tregs in vitro in the absence of Alum via a mechanism that was neutralized by anti-TGF-β and that resulted in the induction of an effector CD69 + CTLA-4 + IFNAR + FOXP3 + Treg subset. In vitro IFN-β + MOG-induced Tregs inhibited EAE when transferred into actively challenged recipients. Unlike IFN-β + NAg in Alum vaccines, vaccination with TGF-β + MOG35-55 in Alum did not increase Treg percentages in vivo. Overall, this study indicates that IFN-β + NAg in Alum vaccination elicits NAg-specific, suppressive CD25 + Tregs that inhibit CNS autoimmune disease. Thus, IFN-β has the activity spectrum that drives selective responses of suppressive FOXP3 + Tregs., Competing Interests: The authors have no financial or commercial conflicts of interest in regard to this work., (Copyright © 2016 by The American Association of Immunologists, Inc.)

A recombinant vaccine containing Aventis Pasteur's canarypox vector (ALVAC)-HIV and gp120 alum decreased the risk of HIV acquisition in the RV144 vaccine trial. The substitution of alum with the more immunogenic MF59 adjuvant is under consideration for the next efficacy human trial. We found here that an ALVAC-simian immunodeficiency virus (SIV) and gp120 alum (ALVAC-SIV + gp120) equivalent vaccine, but not an ALVAC-SIV + gp120 MF59 vaccine, was efficacious in delaying the onset of SIVmac251 in rhesus macaques, despite the higher immunogenicity of the latter adjuvant. Vaccine efficacy was associated with alum-induced, but not with MF59-induced, envelope (Env)-dependent mucosal innate lymphoid cells (ILCs) that produce interleukin (IL)-17, as well as with mucosal IgG to the gp120 variable region 2 (V2) and the expression of 12 genes, ten of which are part of the RAS pathway. The association between RAS activation and vaccine efficacy was also observed in an independent efficacious SIV-vaccine approach. Whether RAS activation, mucosal ILCs and antibodies to V2 are also important hallmarks of HIV-vaccine efficacy in humans will require further studies.

Accumulated evidence obtained from various clinical trials and animal studies suggested that cancer vaccines need better adjuvants than those that are currently licensed, which include the most commonly used alum and incomplete Freund's adjuvant, because of either a lack of potent anti-tumor immunity or the induction of undesired immunity. Several clinical trials using immunostimulatory adjuvants, particularly agonistic as well as non-agonistic ligands for TLRs, C-type lectin receptors, retinoic acid-inducible gene I-like receptors and stimulator of interferon genes, have revealed their therapeutic potential not only as vaccine adjuvants but also as anti-tumor agents. Recently, combinations of such immunostimulatory or immunomodulatory adjuvants have shown superior efficacy over their singular use, suggesting that seeking optimal combinations of the currently available or well-characterized adjuvants may provide a better chance for the development of novel adjuvants for cancer immunotherapy., (© The Author 2016. Published by Oxford University Press on behalf of The Japanese Society for Immunology.)

Statement of Problem: A high percentage of fixed prosthodontic restorations require a subgingival margin placement, which requires the practice of gingival displacement or a deflection procedure to replicate the margins in impression., Purpose: The purpose of this study was to learn the different gingival displacement techniques that are currently used by dentists in their practice and to compare the current concepts of gingival displacement with previously published articles., Materials and Methods: A survey of questions pertaining to gingival deflection methods was distributed as part of continuing education (CE) course material to dentists attending CE meetings in 7 states in the U.S. and 1 Canadian province. Question topics included initial patient assessment procedures, gingival displacement methods, dentist's knowledge and assessment of systemic manifestations, and brand names of materials used., Results: Ninety-four percent of the participants were general practitioners with 24.11 ± 12.5 years of experience. Ninety-two percent used gingival displacement cords, while 20.2% used a soft tissue laser and 32% used electrosurgery as an adjunct. Sixty percent of the dentists used displacement cords impregnated with a medicament. Of the preimpregnated cords, 29% were impregnated with epinephrine, 13% with aluminum chloride, and 18% with aluminum potassium sulfate., Conclusion: The study showed a steady decrease compared with results of previously published articles in the use of epinephrine as a gingival deflection medicament., (Copyright © 2015 Editorial Council for the Journal of Prosthetic Dentistry. Published by Elsevier Inc. All rights reserved.)

Over the past three decades there have been a number of clinical trials directed at interdicting the type 1 diabetes (T1D) disease process in an attempt to prevent the development of the disease in those at increased risk or to stabilize-potentially even reverse-the disease in people with T1D, usually of recent onset. Unfortunately, to date there has been no prevention trial that has resulted in delay or prevention of T1D. And, trials in people with T1D have had mixed results with some showing promise with at least transient improvement in β-cell function compared with randomized control groups, while others have failed to slow the decline in β-cell function when compared with placebo. This Perspective will assess the past and present challenges in this effort and provide an outline for potential future opportunities., (© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.)

Objectives: To review the state of the art and assess future potential in the use of inorganic particulates as vaccine adjuvants., Key Findings: An adjuvant is an entity added to a vaccine formulation to ensure that robust immunity to the antigen is inculcated. The inclusion of an adjuvant is typically vital for the efficacy of vaccines using inactivated organisms, subunit and DNA antigens. With increasing research efforts being focused on subunit and DNA antigens because of their improved safety profiles, the development of appropriate adjuvants is becoming ever more crucial. Despite this, very few adjuvants are licensed for use in humans (four by the FDA, five by the European Medicines Agency). The most widely used adjuvant, alum, has been used for nearly 90 years, yet its mechanism of action remains poorly understood. In addition, while alum produces a powerful antibody Th2 response, it does not provoke the cellular immune response required for the elimination of intracellular infections or cancers. New adjuvants are therefore needed, and inorganic systems have attracted much attention in this regard., Summary: In this review, the inorganic adjuvants currently in use are considered, and the efforts made to date to understand their mechanisms of action are summarised. We then move on to survey the literature on inorganic particulate adjuvants, focusing on the most interesting recent developments in this area and their future potential., (© 2014 Royal Pharmaceutical Society.)

Objectives: Despite scientific literature mentions the application of "water of the 3 sulfates" (copper sulphate, zinc sulphate and alum) as a treatment for acute balanitis and balanoposthitis, no clinical trials evaluating its efficacy have been found. In our study we evaluate the efficacy of this solution in acute balanitis and balanoposthitis., Material and Methods: A double-blind randomized study was designed to compare the efficacy of "water of the 3 sulfates" (intervention) with saline solution (control) in 50 patients (30 patients and 20 patients, respectively) who suffer from acute balanitis or balanoposthitis. Exudate, erythema, oedema, burning, and itching were the clinical parameters assessed., Results: for all clinical parameters assessed, the outcomes obtained with "water of the 3 sulfates" are higher than control, although significant differences only have been found for exudate., Conclusions: in our study, the "water of the 3 sulfates" is significantly more effective than saline solution for removing exudates in acute balanitis and balanoposthitis. Tolerability was excellent in both treatments., (Copyright © 2014 AEU. Publicado por Elsevier España, S.L.U. All rights reserved.)

We report a case of laparoscopic surgery for a rectal carcinoid after aluminum potassium and tannic acid (ALTA) therapy for an internal hemorrhoid. A 66-year-old man was admitted to our hospital because of bleeding during defecation. He was diagnosed via anoscopy with Goligher grade II internal hemorrhoids. Examination via colonoscopy revealed 2 yellowish submucosal tumors in the lower rectum that were 5mm and 10mm in diameter. A rectal carcinoid tumor was diagnosed based on histopathology. Abdominal computed tomography demonstrated no metastases to the liver or lymph nodes. First, we performed ALTA therapy for the internal hemorrhoids. Two weeks later, we performed laparoscopic-assisted low anterior resection (D2) for the rectal carcinoid. The patient was discharged without complications and has not experienced recurrence during the 2 years of follow-up care.

Background: This study aimed to analyse data from two different studies (phase II and phase III) regarding the safety and efficacy of treatment with alum formulated glutamic acid decarboxylase GAD65 (GAD-alum) at 30 months after administration to children and adolescents with type 1 diabetes., Methods: The phase II trial was a double-blind, randomised placebo-controlled study, including 70 children and adolescents who were followed for 30  months. Participants received a subcutaneous injection of either 20 µg of GAD-alum or placebo at baseline and 1 month later. During a subsequent larger European phase III trial including three treatment arms, participants received two or four subcutaneous injections of either 20 µg of GAD-alum and/or placebo at baseline, 1, 3 and 9  months. The phase III trial was prematurely interrupted at 15 months, but of the 148 Swedish patients, a majority completed the 21 months follow-up, and 45 patients completed the trial at 30 months. Both studies included GAD65 auto-antibodies-positive patients with fasting C-peptide ≥ 0.10 nmol/l. We have now combined the results of these two trials., Results: There were no treatment related adverse events. In patients treated with 2 GAD-alum doses, stimulated C-peptide area under the curve had decreased significantly less (9  m: p  <  0.037; 15 m: p  <  0.032; 21 m: p  <  0.003 and 30  m: p <  0.004), and a larger proportion of these patients were also able to achieve a peak stimulated C-peptide > 0.2  nmol/L (p  <  0.05), as compared with placebo., Conclusion: Treatment with two doses of GAD-alum in children and adolescents with recent-onset type 1 diabetes shows no adverse events and preserves residual insulin secretion., (Copyright © 2013 John Wiley & Sons, Ltd.)

Objectives: Canine atopic dermatitis is a very common disease in small animal practice. Its only specific treatment is allergen immunotherapy. In rush-immunotherapy (RIT) increasing doses of allergen extract are injected subcutaneously in short intervals. Maintenance doses are achieved within one day compared to weeks or months with conventional immunotherapy. The aim of this study was to evaluate the safety and efficacy of RIT with alum-precipitated allergens., Materials and Methods: A series of 20 dogs with atopic dermatitis underwent RIT with alum-precipitated allergens. Pruritus and medications at the start of the immunotherapy and 12 months afterwards were compared and adverse effects were recorded., Results: Significant improvement in pruritus (p = 0.0001) and medication scores (p = 0.0004) was noted after approximately 12 months of treatment. The observed clinical response was good to excellent in 70% of the dogs, consistent with other published reports. One dog vomited once during the induction day, with no other clinical problems and completion of the normal protocol. The other 19 dogs showed no adverse effects at all during or after RIT., Conclusion and Clinical Relevance: RIT with alum-precipitated allergens seems to be a safe and efficacious method to treat dogs with atopic dermatitis.

Conventional hemorrhoidectomy is applied for the treatment of prolapsing internal hemorrhoids. Recently, less-invasive treatments such as sclerotherapy using aluminum potassium sulphate/tannic acid (ALTA) and a procedure for prolapse and hemorrhoids (PPH) have been introduced. We compared the results of sclerotherapy with ALTA and an improved type of PPH03 with those of hemorrhoidectomy. Between January 2006 and March 2009, we performed hemorrhoidectomy in 464 patients, ALTA in 940 patients, and PPH in 148 patients with second- and third-degree internal hemorrhoids according to the Goligher's classification. The volume of ALTA injected into a hemorrhoid was 7.3 ± 2.2 (mean ± SD) mL. The duration of the operation was significantly shorter in ALTA (13 ± 2 minutes) than in hemorrhoidectomy (43 ± 5 minutes) or PPH (32 ± 12 minutes). Postoperative pain, requiring intravenous pain medications, occurred in 65 cases (14%) in hemorrhoidectomy, in 16 cases (1.7%) in ALTA, and in 1 case (0.7%) in PPH. The disappearance rates of prolapse were 100% in hemorrhoidectomy, 96% in ALTA, and 98.6% in PPH. ALTA can be performed on an outpatient basis without any severe pain or complication, and PPH is a useful alternative treatment with less pain. Less-invasive treatments are beneficial when performed with care to avoid complications.

Particulates and crystals stimulate the immune system to induce inflammatory responses. Several nanometer- to micrometer-sized particulates, such as particle matter 2.5 (PM2.5), diesel particles, and sand dust, induce pulmonary inflammation and allergic asthma. Conversely, nanometer- to micrometer-sized crystal, sphere, and hydrogel forms of aluminum salts (referred to as "alum") have been used as vaccine adjuvants to enhance antibody responses in animals and humans. Although most of these particulates induce type-2 immune responses in vivo, the molecular and immunological mechanisms of action as a vaccine adjuvant are poorly understood. In this review, recent advances in particulate adjuvant research from the standpoint of innate immune responses are discussed.

Aims: We have previously shown that two injections of glutamic acid decarboxylase formulated in alum (GAD-alum) preserved residual insulin secretion in children and adolescents with recent onset type 1 diabetes (T1D), and was accompanied by increased GAD autoantibody (GADA) titers. The aim of this study was to investigate whether GAD-alum treatment affected the GADA epitope pattern., Methods: Serum samples from patients treated with GAD-alum (n = 33) or placebo (n = 27), at baseline, 1, 3, 9, and 15 months after the initial injection, were tested for their binding capacity to specific GADA epitopes in an epitope-specific radioligand binding assay with six recombinant Fab (rFab) (b96.11, DPA, DPD, MICA3, b78, and N-GAD(65) mAb)., Results: No significant differences in variability of binding to any of the tested rFab were observed from baseline to 15 months. There was a sustained low binding of GADA to the b78- and N-GAD(65) mAb-defined epitopes, often recognized by GADA in patients with stiff person syndrome (SPS) and seldom in T1D patients. However, binding of GADA to the T1D-associated b96.11-defined epitope increased between baseline and 3 months in GAD-alum (-8.1%, min -72.4%, max 39.6%) compared to placebo patients (1.5%, min -28.3%, max 28.6%) (p = 0.02). Subsequently, the b96.11-defined epitope recognition returned to levels similar to that observed at baseline., Conclusions: GAD-alum injections did not affect binding of GADA to SPS-related epitopes, further supporting the safety of the treatment. There were no changes in GADA epitope specificity to the T1D-related epitopes, except for a temporarily increased binding to one of the tested epitopes., (© 2011 John Wiley & Sons A/S.)

Due to the poor immunogenicity of subunit protein antigens, there is a need to use adjuvants in order to generate effective immune responses. Basic fibroblast growth factor (bFGF) is one of the best characterized pro-angiogenic cytokine and is a candidate target for anticancer therapy. We used truncated bFGF (tbFGF) combined with engineered pVAX-nCpG as novel adjuvant to immunize mice in order to inhibit tumor angiogenesis and suppress tumor growth. In our study, the results demonstrated that the mice immunized with tbFGF-alum-pVAX-8CpG produced a better tumor-suppression effect compared with the other groups, apart from the group treated with tbFGF-alum-CpG. In addition, the function of immune modulation of pVAX-8CpG was similar to CpG ODNs. The vaccine composed of tbFGF, alum and pVAX-8CpG effectively inhibited tumor angiogenesis and induced strong antitumor immune responses. The antitumor activity induced by the vaccine tbFGF-alum-pVAX-8CpG was not only associated with the antigen-specific antibody, but also with the killing activity of cytotoxic cells. This indicates that alum-pVAX-8CpG may be an innovative adjuvant for cancer vaccines.

Purpose of Review: To update on the clinical trials using antigen-specific therapies in autoimmune diabetes., Recent Findings: Type 1 diabetes is now a predictable disease with the measurement of islet autoantibodies, and the incidence is increasing dramatically. Well tolerated and effective interventions are needed to stop the underlying autoimmune destruction of insulin-producing beta cells. Beta-cell antigens, insulin and glutamic acid decarboxylase, are being used to preserve endogenous insulin production in individuals with new-onset diabetes and to prevent diabetes. The results of antigen-specific immune intervention trials are reviewed and consideration is given to future directions for inducing tolerance in type 1 diabetes., Summary: Antigen-specific immune therapies act by enhancing regulatory T cell function, in animal models often locally and selectively in islets or pancreatic lymph nodes while inhibiting effector T cells. This therapeutic pathway provides a safe treatment to preserve beta cell function in new-onset diabetic individuals with the GAD-Alum vaccine being the most extensively studied therapy. Insulin is being used in many forms to prevent diabetes and stop the underlying autoimmune process. For the future, combination immune therapies targeting different pathways in the immune system will be needed to effectively induce sustained tolerance in type 1 diabetes.

We have previously shown that two injections of 20 μg GAD-alum to recent onset type 1 diabetic children induced GADA levels in parallel to preservation of insulin secretion. Here we investigated if boosted GADA induced changes in IgG1, 2, 3 and 4 subclass distributions or affected GAD(65) enzyme activity. We further studied the specific effect of GAD-alum through analyses of IA-2A, tetanus toxoid and total IgE antibodies. Serum from children receiving GAD-alum or placebo was collected pre-treatment and after 3, 9, 15 and 21 months. At 3 months a reduced percentage of IgG1 and increased IgG3/IgG4 were detected in GAD-alum treated. Further, IA-2A, IgE and tetanus toxoid antibodies, as well as GAD(65) enzyme activity, were unaffected confirming the specific effect of treatment. In the GAD-alum group, higher pre-treatment GADA were associated to more pronounced C-peptide preservation. The induced IgG3/IgG4 and reduced IgG1 suggest a Th2 deviation of the immune response., (Copyright © 2010 Elsevier Inc. All rights reserved.)

Major full-thickness burn injuries in newborns are rare but have been reported following the use of medical and warming devices during the early neonatal period. In this report, we present a newborn infant with major full-thickness contact burn injuries of 15% of the total body surface area (TBSA) caused by a water-filled warming bottle applied to the naked skin, and describe the sequential progress of epidermal necrosis and wound healing with autografting.

Background: The literature is replete with studies establishing Streptococcus mutans as a major player in the formation of pit and fissure caries in all dentitions. Salivary bacterial levels in turn are related to the number of colonized surfaces. Therefore, decreasing the salivary levels of S. mutans would have a great benefit in decreasing the incidence of dental diseases., Aims: Keeping in mind the potential antimicrobial effects of saturated saline and alum solutions, the present study was attempted to compare and evaluate the effects of saturated saline rinse and 0.02 M alum mouthrinse on salivary S. mutans levels in children., Materials and Methods: The investigation was a double-blind, stratified comparison of three parallel groups of children who used either saturated saline rinse, 0.02 M alum mouthrinse or distilled water (placebo) rinse twice daily under professional supervision for a 21-day period. A total of three saliva samples were taken from each individual - at baseline, on the 10 th day and on the 21 st day, and colony counts of S. mutans were determined. All data were subjected to statistical analysis using Wilcoxon's Signed Ranks Sum and Mann-Whitney "U" test., Results and Conclusions: Children using saturated saline rinse and alum rinse showed statistically significant reductions in salivary S. mutans counts after 10 days and also after 21 days. After 21 days, the saturated saline rinse and alum rinse groups showed statistically significant differences over the placebo rinse group. Again, the alum rinse group showed a statistically significant difference over the saturated saline rinse group.

Importance of the Field: Type 1 diabetes is a common and very serious disease. There has been very active research going on for a long time aiming at preservation of the residual insulin secretion by some kind of intervention to stop the destructive autoimmune process. This review covers a new type of immune intervention using auto-antigen treatment., Areas Covered in This Review: Immune interventions in type 1 diabetes have been tried during the last 30 years, this review mentions some of them, but the main topic is the use of the auto-antigen glutamic acid decarboxylase (GAD) to create tolerance to stop the autoimmune process. The clinical trials have been performed during the last 15 years and are all covered., What the Reader Will Gain: This review will give the reader a picture of the research behind treatment with GAD as an immune intervention in type 1 diabetes., Take Home Message: The key finding so far is that treatment with Diamyd has not only been shown to preserve residual beta cell function in type 1 diabetes, but this treatment may be the proof in humans of a new concept of treating and perhaps even preventing autoimmune diseases.

Background: Aquagenic acrokeratoderma (AA) is a rare condition with female predilection that occurs after brief water exposure and disappears minutes to an hour after drying. The pathogenesis remains unclear., Methods: Four Chinese patients with AA were reported and analyzed., Results: There were 2 males and 2 females (age range: 14-33 years) who presented with a 2-week to more than 10-year history of small white papules coalescing into edematous plaques on the hands; lesions appeared within 5-10 minutes of water exposure, began to regress in 3-20 minutes and disappeared within 5 minutes to one hour after drying. Warm water provoked the lesions more rapidly than cold water. Lesions of a female patient could be triggered by detergent. In another female patient, lesions also involved the feet and were associated with palmoplantar erythema and hyperhidrosis. Biopsy from the lesion of one patient after water exposure revealed hyperkeratosis, mild hypergranulosis, and dilatated eccrine ducts. Biopsy from the lesion of another patient after drying showed normal epidermis and dermis. Two patients were treated with topical formalin 3% in alcohol, and two with 3% potassium aluminium sulfate solution with partial relief without any adverse effects., Conclusion: AA may occur in both males and females and may involve the feet. Warm water triggers the lesions more rapidly than cold. Topical formalin 3% in alcohol and 3% potassium aluminium sulfate solution may be optional therapy.

Background: We retrospectively compared the results of sclerotherapy with a new sclerosing agent (aluminum potassium sulphate/tannic acid) and hemorrhoidopexy using an improved type of circular stapler with hemorrhoidectomy., Methods: Between January 2006 and September 2008, we performed hemorrhoidectomy in 416 patients, sclerotherapy in 784 patients and hemorrhoidopexy in 118 patients with prolapsing internal hemorrhoids., Results: The median volume of the agent injected into a hemorrhoid was 7 ml (interquartile range = 4). The operation duration was significantly shorter (p < 0.01) in sclerotherapy, 13 min (interquartile range = 7), than in hemorrhoidectomy, 43 min (interquartile range = 15), and hemorrhoidopexy, 31 min (interquartile range = 16). Postoperative pain, needing pain killer injection, occurred in 59 patients (14%) in hemorrhoidectomy, 14 patients (1.8%) in sclerotherapy and 1 patient (0.8%) in hemorrhoidopexy (p < 0.01). The disappearance rates of prolapse were 100% (416/416 patients) in hemorrhoidectomy, 96% (753/784 patients) in sclerotherapy and 98.3% (116/118 patients) in hemorrhoidopexy., Conclusions: Hemorrhoidectomy, widely applied for hemorrhoids, needs hospitalization, being accompanied by pain. Sclerotherapy could be performed on outpatient bases without any severe pain or complication. Hemorrhoidopexy is a useful alternative treatment with less pain. Less invasive treatments would be useful when performed paying attention to avoid complications., (Copyright © 2010 S. Karger AG, Basel.)

Strategies aimed at treating atherosclerosis by immunization protocols are emerging. Such protocols commonly use adjuvants as non-specific stimulators of immune responses. However, adjuvants are known to modify various disease processes. The aim of this study was to determine whether adjuvants alter the development of atherosclerosis. We performed immunization protocols in apolipoprotein E knockout mice (E degrees ) following chronic administration schedules commonly employed in experimental atherosclerosis. Our results point out a dramatic effect of several adjuvants on the development of atherosclerosis; three of the four adjuvants tested reduced lesion size. The Alum adjuvant, which is the adjuvant currently used in most vaccination protocols in humans, displayed a strong atheroprotective effect. Mechanisms accounting for atheroprotective effect of Freund's adjuvants included their capacity to increase both Th2 responses and anti-MDA-LDL IgM titers, and/or to impose atheroprotective lipoprotein profiles. The present study indicates that adjuvants have potent atheromodulating capabilities, and thus, implies that the choice of adjuvant is crucial in long-term immunization protocols in experimental atherosclerosis.

Despite the existence for some time of effective prophylactic vaccines, hepatitis B virus (HBV) infection remains an important global concern. Improvements on existing vaccines could be beneficial, especially in situations where it is desirable or necessary to induce protective immunity more rapidly or with fewer doses. We have compared, in chimpanzees, a current HBV vaccine that contains recombinant hepatitis B surface antigen HBsAg) adsorbed to alum, with two novel vaccine strategies that have proven superior to the current vaccine in mice. The first approach was the use of oligodeoxynucleotides containing CpG motifs (CpG ODN) as an adjuvant to Engerix-B, a commercial HBV vaccine. The addition of CpG ODN to Engerix-B greatly improved the kinetics and magnitude of the humoral response, suggesting that CpG ODN might allow induction of protective immunity in humans more quickly and with fewer vaccine doses. All animals receiving either control or CpG-containing subunit vaccines at 0 and 4 weeks attained titers of HBsAg-specific antibody (anti-HBs) considered protective (> or =10 mIU/ml) and were indeed protected from challenge at 8 weeks with 10(3.5) 50% chimp infectious doses (CID(50)) of intravenous HBV. The second approach was a DNA vaccine with a plasmid vector optimized for content of immunostimulatory CpG motifs. Despite the fact that earlier studies had shown four doses of a similar DNA vaccine (except not optimized for CpG content) to induce strong humoral responses in 1 of 2 chimpanzees, in this study two doses of DNA vaccine (at 0 and 4 weeks) did not generate any detectable anti-HBs in either of 2 chimpanzees, although it did protect 1 that rapidly developed anti-HBs during the incubation period, suggesting priming of an antibody response. The poor results may be due to an inadequate number of doses or amount of plasmid DNA in these larger animals, but nevertheless point to the need to improve delivery methods for DNA vaccines for use in larger animals such as primates.

Herpes simplex virus (HSV) Type-1 and -2 are common infections that can cause primary and recurrent herpes labialis and genitalis, as well as gingivostomatitis, keratoconjunctivitis, encephalitis, disseminated infections in immunocompromised persons and neonatal infections. Despite several decades of HSV vaccine development, no effective vaccine has been developed until recently. The following review of the genital HSV-2 glycoprotein D (gD2t, t is for truncated) subunit vaccine formulated with a new adjuvant (AS04) containing alum and 3-O deacylated monophosphoryl lipid A (MPL) provides a background in which to evaluate the vaccine as well as a brief review of other approaches to herpes vaccines. The gD2t-AS04 vaccine has been demonstrated to be safe in several large clinical trials. In two trials, the vaccine reduced genital herpes disease by 73 and 74%, but only in females with no previous HSV infection. A large ongoing trial in HSV seronegative females will provide additional data on protection from HSV disease and infection.

Aim: Studies on vaccines against the periodontal pathogen Porphyromonas gingivalis have produced conflicting results, but no consideration has been given to the role of different adjuvants in these vaccines. We have previously shown that an intra-chamber challenge with heat-killed P. gingivalis was modified by immunization with different adjuvants. This study tested the hypothesis that different adjuvants in P. gingivalis vaccines would differentially modify the host response to a live P. gingivalis infection., Results: Using P. gingivalis-infected subcutaneous chambers in mice, we show that vaccination with P. gingivalis in alum attenuated the pro-inflammatory cytokine levels at the site of infection, while the vaccine containing incomplete Freund's adjuvant did the opposite. Although both vaccines induced a similar humoral IgG response, P. gingivalis-induced abscesses were significantly smaller in the alum-adjuvant group., Conclusions: The results suggest that the immune response and the resultant protection to a P. gingivalis infection, in P. gingivalis-vaccinated mice, are adjuvant-dependent.

Traditionally known as a haemostatic agent, alum shows a paradoxical effect of increased prothrombin and partial thromboplastin times. This study investigated the in vivo effect of alum on platelet aggregation and bleeding time in rabbits. The collagen-induced platelet aggregation of platelet-rich plasma samples from 14 healthy rabbits was measured turbidometrically using a platelet aggregometer, before and 1 hour after intravenous injection of alum. Collagen-induced platelet aggregation was significantly reduced after alum injection. Bleeding time from an ear puncture in 8 rabbits was also significantly prolonged after intravenous alum injection. These results suggest that the use of alum as an oral antiplatelet drug could be explored further, taking into account possible side-effects especially in renal compromised patients.

Purpose of Review: Inclusion of adjuvants in immunotherapy vaccines are important to enhance immune responses to allergens. This article will cover the recent advances in adjuvant formulations described in published articles primarily over the past 2 years., Recent Findings: Traditionally, allergen immunotherapy preparations utilize aluminium hydroxide as an adjuvant. These have generally proved efficacious and have a good safety profile. However, recent advances in the understanding of immunological mechanisms underlying immunotherapy and in the design of new adjuvants may allow a more rational approach to adjuvant use. One approach is to use adjuvants such as immunostimulatory sequences or monophosphoryl lipid A, which can deviate allergy-associated Th2 immune responses towards a Th1 phenotype. Both of these adjuvants have been used in pilot controlled clinical trials which have demonstrated clinical efficacy and the induction of protective IgG antibodies. Other approaches to improve immunotherapy vaccines include microencapsulation of allergen to allow delivery of the allergen directly to the gut in order to induce immunological tolerance and vaccination with heat-killed mycobacteria., Summary: There is great interest in newly designed adjuvants to improve the efficacy and safety of allergen immunotherapy. A better understanding of immunological mechanisms and further clinical trials utilizing new adjuvants are needed.

Aluminium adjuvants are the most widely used adjuvants in both human and veterinary vaccines. These adjuvants have been used in practical vaccination for more than 60 years and are generally recognized as safe and as stimulators of Th2 immunity. The present review gives a short introduction to the pioneering research at the start of the use of aluminium compounds as adjuvants, including references on the chemistry of these compounds. Analytical methods for identifying the most commonly used aluminium compounds, such as boehmite and aluminium hydroxyphosphate, are mentioned. Emphasis is placed on the important factors for antigen adsorption and on the latest work using gene-deficient mice in the research of the mechanism of aluminium adjuvants in terms of cytokine and T-cell subset stimulation. Key references on the ability of aluminium adjuvants to stimulate IgE and also in vivo clearing of aluminium adjuvants are discussed. Furthermore, the review addresses the issue of local reactions in the context of injection route and local tissue disturbance. Possible new applications of aluminium adjuvants in, for example, combined aluminium-adsorbed protein and DNA oligonucleotide vaccines as well as the possible use of aluminium adjuvants in combination with IL-12 to stimulate Th1-type immune responses are mentioned., (Copyright 2004 Australasian Society for Immunology Inc.)

The problem with pure recombinant or synthetic antigens used in modern day vaccines is that they are generally far less immunogenic than older style live or killed whole organism vaccines. This has created a major need for improved and more powerful adjuvants for use in these vaccines. With few exceptions, alum remains the sole adjuvant approved for human use in the majority of countries worldwide. Although alum is able to induce a good antibody (Th2) response, it has little capacity to stimulate cellular (Th1) immune responses which are so important for protection against many pathogens. In addition, alum has the potential to cause severe local and systemic side-effects including sterile abscesses, eosinophilia and myofascitis, although fortunately most of the more serious side-effects are relatively rare. There is also community concern regarding the possible role of aluminium in neurodegenerative diseases such as Alzheimer's disease. Consequently, there is a major unmet need for safer and more effective adjuvants suitable for human use. In particular, there is demand for safe and non-toxic adjuvants able to stimulate cellular (Th1) immunity. Other needs in light of new vaccine technologies are adjuvants suitable for use with mucosally-delivered vaccines, DNA vaccines, cancer and autoimmunity vaccines. Each of these areas are highly specialized with their own unique needs in respect of suitable adjuvant technology. This paper reviews the state of the art in the adjuvant field, explores future directions of adjuvant development and finally examines some of the impediments and barriers to development and registration of new human adjuvants., (Copyright 2004 Australasian Society for Immunology Inc.)

Acute aluminum intoxication is uncommon in clinical practice but can be fatal. This limited experience is reflected in the paucity of data assessing a viable approach to the treatment of these patients. In this report, the authors describe the clinical course and successful, pharmacokinetic-based deferoxamine-hemodialysis treatment regimen of a patient with severe aluminum encephalopathy following alum bladder irrigation. The combined use of deferoxamine and appropriately timed hemodialysis appears to be a very reasonable means of treating patients with severe acute aluminum intoxication.

Background: Xiao zhi ling (XZL), which consists of Chinese nutgalls and aluminium potassium sulphate, is used as a local injection for the treatment of internal haemorrhoids in China. It is also used for endoscopic sclerotherapy of oesophageal varices. To date, however, it has not been compared with other sclerosants with regard to its safety and efficacy., Methods: In the present study, the effect on the endothelium and the haemolytic and thrombosing effects of XZL were compared with those of 5% ethanolamine oleate and 1% polidocanol, using an endothelial cell line and red blood cells taken from rats and the dorsal marginal ear vein of rabbits. In addition, XZL was injected into the area surrounding varices in rats and its efficacy was studied endoscopically and histologically., Results: Xiao zhi ling reduced the size of varices in rats after causing severe damage in the injected region. Compared with the other two sclerosants, however, XZL had little effect on the endothelium and was the least haemolytic compound. Furthermore, XZL did not cause thrombosis in the injected vein of a rabbit., Conclusions: These results suggest that XZL is another type of sclerosant with astringent rather than detergent properties. This compound should be used to treat oesophageal varices by paravariceal injection in smaller doses than 5% ethanolamine oleate and 1% polidocanol.