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PubMed2001

Managing ammonia emissions from dairy cows by amending slurry with alum or zeolite or by diet modification.

Animal agriculture is a significant source of atmospheric ammonia. Ammonia (NH3) volatilization represents a loss of plant available N to the farmer and a potential contributor to eutrophication in low-nitrogen input ecosystems. This research evaluated on-farm slurry treatments of alum or zeolite and compared three diets for lactating dairy cows in their effectiveness to reduce NH3 emissions. NH3 emissions were compared using a group of mobile wind tunnels. The addition of 2.5% alum or 6.25% zeolite to barn-stored dairy slurry reduced NH3 volatilization by 60% and 55%, respectively, compared to untreated slurry. The alum conserved NH3 by acidifying the slurry to below pH 5, while the zeolite conserved ammonia by lowering the solution-phase nitrogen through cation exchange. The use of alum or zeolite also reduced soluble phosphorus in the slurry. NH3 loss from fresh manure collected from lactating dairy cows was not affected by three diets containing the same level of crude protein but differing in forage source (orchardgrass silage vs. alfalfa silage) or neutral detergent fiber (NDF) content (30% vs. 35% NDF). NH3 losses from the freshly excreted manures occurred very rapidly and included the urea component plus some unidentified labile organic nitrogen sources. NH3 conservation strategies for fresh manures will have to be active within the first few hours after excretion in order to be most effective. The use of alum or zeolites as an on-farm amendment to dairy slurry offers the potential for significantly reducing NH3 emissions.

Alum Compounds↗
PubMed1996

A1 toxicity in yeast. A role for Mg?

We have established conditions in which soluble Al is toxic to the yeast Saccharomyces cerevisiae. The major modifications to a standard synthetic medium were lowering the pH and the concentration of Mg ions. Alterations to the PO4, Ca, or K concentration had little effect on toxicity. Organic acids known to chelate Al reduced its toxicity, suggesting that Al3+ is the toxic Al species. The unique ability of Mg ions to ameliorate Al toxicity led us to investigate the hypothesis that Al inhibits Mg uptake by yeast. Yeast cells accumulate Mg, Co, Zn, Ni, and Mn ions via the same transport system (G.F. Fuhrmann, A. Rothstein [1968] Biochim Biophys Acta 163: 325-330). Al3+ inhibited the accumulation of 57Co2+ by yeast cells more effectively than Ga, La, or Mg. In addition, a mutant yeast strain with a defect in divalent cation uptake proved to be more sensitive to Al than a wild-type strain. Taken together, these results suggest that Al may cause Mg deficiency in yeast by blocking Mg transport. We discuss the relevance of yeast as a model for the study of Al toxicity in plant systems.

Alum Compounds↗
PubMed1998

Aluminum induces oxidative stress genes in Arabidopsis thaliana.

Changes in gene expression induced by toxic levels of Al were characterized to investigate the nature of Al stress. A cDNA library was constructed from Arabidopsis thaliana seedlings treated with Al for 2 h. We identified five cDNA clones that showed a transient induction of their mRNA levels, four cDNA clones that showed a longer induction period, and two down-regulated genes. Expression of the four long-term-induced genes remained at elevated levels for at least 48 h. The genes encoded peroxidase, glutathione-S-transferase, blue copper-binding protein, and a protein homologous to the reticuline:oxygen oxidoreductase enzyme. Three of these genes are known to be induced by oxidative stresses and the fourth is induced by pathogen treatment. Another oxidative stress gene, superoxide dismutase, and a gene for Bowman-Birk protease inhibitor were also induced by Al in A. thaliana. These results suggested that Al treatment of Arabidopsis induces oxidative stress. In confirmation of this hypothesis, three of four genes induced by Al stress in A. thaliana were also shown to be induced by ozone. Our results demonstrate that oxidative stress is an important component of the plant's reaction to toxic levels of Al.

Alum Compounds↗
PubMed2004

Vaccine adjuvants: current state and future trends.

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.

Adjuvants, Immunologic↗
PubMed1989

Transmission of virus particles by cryotherapy and multi-use caustic pencils: a problem to dermatologists?

The possibility of transmission of virus particles from patient to patient by multi-use silver nitrate sticks and styptic pencils and by cotton wool swabs that have been dipped repeatedly into Dewar flasks of liquid nitrogen was studied. The results showed that transmission by the sticks and pencils is unlikely but that virus particles can be transferred into and out of a Dewar flask on cotton wool swabs. We suggest that swabs should not be dipped repeatedly into the flask of liquid nitrogen but that, instead, a small aliquot of nitrogen should be decanted into a smaller 'clean' vessel and a new cotton swab used for each patient.

Adenoviruses, Human↗
PubMed1976

A comparative trial of hyposensitization in 1973 in the treatment of hay fever using Pollinex and Alavac-P.

A direct comparison was made in 112 hay fever patients of hyposensitization treatment with glutaraldehyde-pollen-tyrosine adsorbate (Pollinex) and with alum-precipitated pyridine extract (Alavac-P) which is an accepted form of treatment, its efficacy having been shown by a comparative trial against a placebo preparation. No significant difference could be detected between the results of the two forms of treatment. Seventy-seven per cent of patients responded with improvement following treatment with the tyrosine adsorbed vaccine, and 81% of those receiving the alum-precipitated vaccine. Side effects from treatment, both local and general, were generally of an infrequent or mild nature for both vaccines.

Adolescent↗
PubMed1978

Occupational asthma in Finland.

In Finland occupational asthma caused by protein allergens and reactive chemicals present in the air of work environments is increasing. This communication describes provocative challenge tests and methods for measuring exposure under simulated work conditions. The importance of lung function measurements during non-exposure and placebo periods is stressed. Especially late reactions are difficult to assess because of the great circadian variation in the lung function parameters of asthmatics. For a positive challenge test, a decrease in peak flow values of at least 15% and a clear deviation from normal circadian variation and placebo periods is required. The allergens of vegetable or animal origin primarily affect patients with an atopic constitution. Chemical allergens seem to attack all exposed workers in the same way. The report lists the occupations with risk for asthma and refers to the population at risk; bakers seem to be the group with the most risk. The importance of early diagnosis, removal of the worker from exposure and improvement of the hygienic aspects of the work environment are stressed.

Air Pollutants↗
PubMed1995

Immunotherapy with Alpare in patients with respiratory allergy to Parietaria pollen: a two year double-blind placebo-controlled study.

Allergy to Parietaria judaica pollen causes significant morbidity in many areas of the world. In addition to rhinitis, patients who are allergic to this pollen have a high incidence of asthma. The pollinating season is long, making this particular allergy challenging for clinicians to treat. This study was designed to determine if immunotherapy with an alum adsorbed partially purified Parietaria extract (Alpare Parietaria) containing a targeted maintenance dose of 12,500 BUs was effective in decreasing rhinitis symptoms in patients allergic to Parietaria. Using a double-blind placebo-controlled technique 36 patients received placebo or active extract for 2 years. Twenty (11 placebo and nine active) completed the 2 year study. Efficacy of treatment was evaluated by determining changes in skin reactivity, visual analog scores, diary symptom scores and end of study assessments. Reactions were monitored as well. Skin-test suppression was marginally significant in the actively treated group after 1 year and showed even more significant suppression after the second year. Nasal block, rhinorrhoea and sneezing all were significantly decreased in the active group. The nasal provocation test did not show a significant change after 1 year, in either group, but after 2 years of treatment the active group did show significant improvement. Although almost all patients in the actively treated group experienced local reactions, the incidence of systemic reactions was not different between the two groups. In conclusion, immunotherapy with this extract at this dose was effective in ameliorated rhinitis symptoms in patients allergic to Parietaria judaica.

Adolescent↗
PubMed2004

Oral administration of bovine whey proteins to mice elicits opposing immunoregulatory responses and is adjuvant dependent.

Most studies investigating the induction of oral tolerance (OT) use purified proteins such as ovalbumin (OVA), bovine serum albumin (BSA) and beta-lactoglobulin (beta-LG). Little information is available regarding the induction of OT to a protein mixture, e.g. cow's milk. In this study we compared the regulatory mechanisms induced after the oral administration of a whey protein concentrate (WP) derived from cow's milk following immunization with two different adjuvants, complete Freund's adjuvant (CFA) and alum. OVA was used as a control antigen. Animals were given a single feed of these proteins at an equivalent dose of 1 mg/g body weight before they were immunized seven days later with the antigen in Freund's adjuvant or alum. Delayed type hypersensitivity (DTH) responses were suppressed by both a feed of WP and OVA after immunization with CFA. However, only OVA feeding suppressed antigen specific IgG responses. In an attempt to investigate whether WP would tolerize the more susceptible IgE responses, alum immunization replaced CFA as the adjuvant used for systemic immunizations. WP, after a single feed, significantly primed for DTH and IgE responses indicating oral sensitization to WP. In contrast, OVA suppressed DTH, IgE and IgG responses. Antigen specific proliferation of mononuclear cells was suppressed in mice fed OVA, but primed in those fed with WP. In addition cells taken from sensitized mice fed WP up-regulated levels of specific interleukin (IL) -4, -10 and -12 in vitro whereas these cytokines were suppressed in cultures from tolerant WP fed mice. Global suppression was obtained in cultures from tolerant OVA fed mice. TGF-beta was not detected in draining PLN cell cultures of either tolerant or sensitized mice. These data suggest that a whey protein mixture induces divergent responses following immunization with either CFA or alum despite being fed at an identical dose. We suggest that that the choice of the adjuvant may determine the immunoregulatory outcome and this is also reflected by the systemic cytokine profile.

Administration, Oral↗
PubMed1990

Induction of infertility in female rats after active immunization with 24 kD antigens from rat testes.

A unique polyvalent antiserum against whole washed human sperm was used previously to identify groups of antigens on spermatozoa. The antiserum, designated as Antiserum I, recognized a 40 kD antigen in human sperm extracts. Antiserum I caused agglutination of human sperm and prevented interaction of mouse sperm and oocytes. This serum also recognized a band of 24 kD in rat testicular cytosol. In the present study this group of 24 kD proteins was used as an antigen preparation to actively immunize female rats. Immunization was carried out with two different adjuvants: nor-muramyl dipeptide and SPLPS (a thyalated derivative of lipopolysaccharide). Both groups of animals showed significant antibody titres as detected by indirect immunofluorescence and by sperm agglutination tests. In both groups over 80% of the animals remained infertile, compared to 13% of the controls. It is concluded that a group of antigens in rat testes recognized by Antiserum I offer promise as candidates for a contraceptive vaccine.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed2004

Effect of point-of-use disinfection, flocculation and combined flocculation-disinfection on drinking water quality in western Kenya.

AIMS: Point-of-use drinking water disinfection with sodium hypochlorite has been shown to improve water quality and reduce diarrhoeal disease. However, the chlorine demand of highly turbid water may render sodium hypochlorite less effective. METHODS AND RESULTS: We evaluated a novel combined flocculant-disinfectant point-of-use water treatment product and compared its effect on drinking water quality with existing technologies in western Kenya. In water from 30 sources, combined flocculant-disinfectant reduced Escherichia coli concentrations to <1 CFU100 ml(-1) for 29 (97%) and reduced turbidity to <5 nephelometric turbidity units (NTU) for 26 (87%). By contrast, water from 30 sources treated with sodium hypochlorite reduced E. coli concentrations to <1 CFU 100 ml(-1) for 25 (83%) and turbidity to <5 NTU for 5 (17%). CONCLUSIONS: For source waters over a range of turbidities in western Kenya, combined flocculant-disinfectant product effectively reduces turbidity to <5 NTU and reduces E. coli concentrations to <1 CFU 100 ml(-1). SIGNIFICANCE AND IMPACT OF THE STUDY: The novel flocculant-disinfectant product may be acceptable to consumers and may be effective in reducing diarrhoeal disease in settings where source water is highly turbid.

Alum Compounds↗
PubMed1979

Rates of release of subcutaneously injected antigens in the rat. Comparison of an aqueous preparation with two alum-precipated preparations.

Release of antigen E-125 I from the site of subcutaneous injection in male rats was delayed significantly when either of two alum-precipitated preparations containing 1.0-1.2 mg of Al/ml was administered rather than an aqueous preparation. The rates of 125I excretion were similarly influenced being statistically slower through the first week after single doses of the alum-precipitated preparations. The results of these studies strongly support the view that alum-precipitated vaccines offer more protection from system reactions than aqueous vaccines.

Absorption↗
PubMed1992

Clinical and immunological effects of immunotherapy with alum-absorbed grass allergoid in grass-pollen-induced hay fever.

A double-blind, placebo-controlled study of immunotherapy was conducted in 19 patients with grass-pollen hay fever to evaluate the efficacy and safety of a formalinized depot grass allergoid. The patients were assessed before and during IT by clinical (symptom-medication scores during the grass- pollen season, specific nasal and skin reactivity) and immunological (specific IgE, IgG, IgG1 and IgG4 antibodies) parameters. High doses of grass allergoid, corresponding to a cumulative pre-seasonal dosage of 46,050 PNU, were administered, with only one systemic reaction. The actively treated patients had significantly lower symptom-medication scores than placebo (p less than 0.01) during the month of May and showed a significant decrease in specific skin (p less than 0.01) and nasal (p less than 0.05) reactivity, and a significant early increase in specific IgE (p less than 0.01), IgG (p less than 0.0005), IgG1 (p less than 0.001) and IgG4 (p less than 0.05), with a subsequent decrease of IgE and IgG1. No differences were detected in any of these parameters in the placebo group. A correlation was found between high IgG4/IgG1 ratio and the specific skin reactivity decrease (r = 0.691, p less than 0.05), whereas a high IgG4/IgG1 ratio was associated with higher symptom-medication scores (r = 0.654, p less than 0.05). Possible explanations of these apparent discrepancies are proposed.

Adolescent↗
PubMed1997

Immunotherapy with an alum-adsorbed Parietaria-pollen allergoid: a 2-year, double-blind, placebo-controlled study.

A double-blind, placebo-controlled study was performed in order to confirm the safety, suitability, and efficacy of an alum-adsorbed Parietaria judaica-pollen allergoid, Allergovit, for allergen-specific immunotherapy. Parietaria pollen is an important cause of pollinosis, particularly in the Mediterranean zone, where it may be encountered for up to 8-9 months of the year. It is an aggressive allergen, and the doses tolerated during immunotherapy are less than those achieved with grass pollen. This factor increases the desirability of using therapeutic preparations with minimal IgE-binding activity, such as allergoids, in order to reduce the risk of side-effects and enable patients to tolerate a higher dose of allergen, thereby increasing the chances of successful specific immunotherapy. Forty patients with rhinitis and/or asthma were allocated at random to active- or placebo-treatment groups at the beginning of the study. All patients received the active preparation during the second year of the study. Immunotherapy was well tolerated by all patients and the incidence of side-effects was low. Treatment resulted in significant reductions in specific cutaneous reactivity and increases in nasal tolerance. A progressive improvement in nasal inspiratory peak flow in association with the immunotherapy indicated a reduction in nasal inflammation. These objective assessments of efficacy endorsed the results from the patients' diary cards, which indicated significant improvements in symptoms and reductions in the use of medication. The immunologic activity of the therapeutic preparation was demonstrated by the induction of a significant specific-IgG antibody response, with increases in IgG4 during the second year of treatment. We conclude that the safety and efficacy of immunotherapy with the Parietaria allergoid make it suitable for consideration in the treatment of patients with Parietaria-pollen-induced rhinitis or asthma.

Adolescent↗
PubMed2006

Vaccination of Alzheimer's model mice with Abeta derivative in alum adjuvant reduces Abeta burden without microhemorrhages.

Immunotherapy holds great promise for Alzheimer's disease (AD) and other conformational disorders but certain adverse reactions need to be overcome. The meningoencephalitis observed in the first AD vaccination trial was likely related to excessive cell-mediated immunity caused by the immunogen, amyloid-beta (Abeta) 1-42, and the adjuvant, QS-21. To avoid this toxicity, we have been using Abeta derivatives in alum adjuvant that promotes humoral immunity. Other potential side effects of immunotherapy are increased vascular amyloid and associated microhemorrhages that may be related to rapid clearance of parenchymal amyloid. Here, we determined if our immunization strategy was associated with this form of toxicity, and if the therapeutic effect was age-dependent. Tg2576 mice and wild-type littermates were immunized from 11 or 19 months and their behaviour evaluated prior to killing at 24 months. Subsequently, plaque- and vascular-Abeta burden, Abeta levels and associated pathology was assessed. The therapy started at the cusp of amyloidosis reduced cortical Abeta deposit burden by 31% and Abeta levels by 30-37%, which was associated with cognitive improvements. In contrast, treatment from 19 months, when pathology is well established, was not immunogenic and therefore did not reduce Abeta burden or improve cognition. Significantly, the immunotherapy in the 11-24 months treatment group, that reduced Abeta burden, did not increase cerebral bleeding or vascular Abeta deposits in contrast to several Abeta antibody studies. These findings indicate that our approach age-dependently improves cognition and reduces Abeta burden when used with an adjuvant suitable for humans, without increasing vascular Abeta deposits or microhemorrhages.

Adjuvants, Immunologic↗