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PubMed1994

Some factors controlling carotene destruction by chloroplasts in vitro.

Loss of beta carotene from moist leaf protein stored with a preservative, is closely simulated by the destruction of beta carotene by acetone extracted chloroplasts (stroma) suspended in acetone containing 30% water. During this exposure, stroma lose destructive ability, but it is restored by mercaptoacetate and other reducing agents. Stroma can therefore be used repeatedly. This catalytic process is activated by removing intrinsic inhibitors, predominantly calcium, by extraction at pHs less than 4, or by alum. The objective is to find inhibitors which would be acceptable in a food. That restricts choice. Citrate, tartarate and phosphate are among the more attractive possibilities.

Alum Compounds↗
PubMed1991

High serum aluminium levels and acute reversible encephalopathy in a 4-year-old boy with acute renal failure.

We report a 4-year-old boy, in acute renal failure, who had acute encephalopathy with very high serum aluminium levels (135 micrograms/l [5 mumol/l]) after receiving vesical irrigations with alum. We believe that in situations of non-focal neurological deterioration with no apparent cause in patients with impaired renal function receiving aluminium-containing preparations, the possibility of acute aluminium poisoning should be considered.

Acute Disease↗
PubMed1989

The use of an alum irrigation in the treatment of massive bladder haemorrhage.

Severe, massive bladder haemorrhage is a difficult and often frustrating clinical problem. The aetiologies are numerous and include irradiation, malignancy, severe infection and drug-induced changes. Among the numerous modalities of treatment that have been reported formalin, phenol and silver nitrate instillations have often been associated with significant side effects, morbidity and mortality and have had varying degrees of success. During the last two years we have used continuous closed irrigation of a sterile 0.5% alum solution in 16 patients. Alum is an astringent and acts by protein precipitation over the bleeding surface. Because of a low cell permeability its action is limited to the cell surface and interstitial spaces. The permeability of the cell membrane is reduced but remains viable. The preparation and the pharmaceutical aspects of the 0.5% alum irrigation will be discussed. The conclusion is that the technique of managing massive bladder haemorrhage is simple, efficient, nontoxic and less expensive than previously reported therapies. Therefore, irrigation with alum before instituting invasive means to control bleeding is recommended.

Aged↗
PubMed1976

The effect of graded 60 degrees C 1N nitric acid extraction and of deoxyribonuclease digestion on nuclear staining by metachrome mordant dye metal salt mixtures.

We can divide metachrome mordant staining of nuclei after graded 60 degrees C 1 N nitric acid extraction into three groups. The Feulgen nucleal reaction and dilute cationic dye staining of nuclei are abolished in about 30 minutes. With one group of metachrome dyes nuclear staining is lost with acid exposures of one hour or less. In a second group nuclear staining is weakened by 30-60 minute extractions, but persists in recognizable grade for 4-6 hours. In the third group nuclear staining remains almost unimpaired for 4-6 hours. In the first group the nuclear staining seems clearly assignable to the nucleic acids and to DNA in particular. In the second group loss of part of the reactivity on short exposure indicates some participation of DNA in the control staining result, as well as participation of basic nucleoprotein. In the third group staining seems assignable largely to basic nucleoprotein. The five gallocyanin group dyes, all in group 1, all possess a dialkylamino group, probably functioning as an ammonium chloride.Hematoxylin, the flurone blacks and gallein all present an o-hydroxysemiquinone group which probably acts as a weak acid, in addition to the carboxyl group of gallein which gives the strongest staining of nuclei at the longest acid exposure. Deoxyribonuclease digestion (2 hours, 37 degrees C) separated sharply a class in which nuclear staining failed completely, a class in which nuclear staining was fully equal to that in the control preparations and an intermediate group in which slight, moderate, or severa impairment was present. Generally there was good agreement between the two methods of nucleic acid removal, despite the fixation difference. In each case, however, the extraction procedure was one worked out for the fixation on which it was used.

Alum Compounds↗
PubMed1996

The promotion of iron-induced generation of reactive oxygen species in nerve tissue by aluminum.

Aluminum is suspected to play a role in several neurological disorders. Reactive oxygen species (ROS) lead to oxidative stress, which is thought to be a possible mechanism for neurological damage. Interactions between aluminum and iron, a known promoter of prooxidant events, were studied in cerebral tissues using a fluorescent probe to measure rates of generation of ROS. Al2(SO4)3 alone failed to stimulate ROS production over a wide range of concentrations (50-1000 microM). The aluminum-deferrioxamine chelate in the absence of iron could also not potentiate ROS formation. However, Al2(SO4)3 potentiated FeSO4-induced ROS, with a maximal effect at 10 microM Fe and 500 microM Al. Kaolin, a hydrated aluminum silicate, did not potentiate iron-induced ROS formation. Ferritin had a minor stimulatory effect on ROS generation, but this was not potentiated by the concurrent presence of Al2(SO4)3. Transferrin had no effect on basal rates of ROS generation, but when Al2(SO4)3 was also present, ROS production was enhanced. It is concluded that: 1. There is a potentiation of iron-induced ROS by aluminum salts; 2. Free or complexed aluminum alone is not a key producer of ROS; and 3. High rates of ROS production are unlikely to be owing to the displacement by aluminum iron from its biologically sequestered locations.

Alum Compounds↗
PubMed1998

Phosphorylation sensitizes microtubule-associated protein tau to Al(3+)-induced aggregation.

In Alzheimer's disease the microtubule-associated protein tau becomes hyperphosphorylated and aggregates into paired helical filaments (PHFs). Although the biochemical basis of the aggregation of tau into PHFs is not very clear, Al3+ has been suggested to play some role. Previous studies have shown that Al3+ alters the phosphorylation state and causes aggregation of tau in experimental animals and cultured neurons. In this study Al3+ inhibited phosphorylation of tau by neuronal cdc2-like kinase and dephosphorylation of phosphorylated tau by phosphatase 2B. These inhibitions are very likely due to Al(3+)-induced aggregations of various proteins present in phosphorylation/dephosphorylation assay mixtures since Al3+ caused aggregations of all proteins examined. Furthermore, compared to other proteins, tau displayed only an average sensitivity towards Al(3+)-induced aggregation. However upon phosphorylation, tau's sensitivity towards Al3+ increased 3.5 fold. In the presence of the metal chelator EDTA, Al(3+)-induced aggregates of tau became soluble, whereas Al(3+)-induced phosphorylated tau aggregates were insoluble in the buffer containing EDTA and remained insensitive to proteolysis. Our data suggest that phosphorylation sensitizes tau to Al3+ and phosphorylated tau transforms irreversibly into a phosphatase and protease resistant aggregate in presence of this metal ion.

Alum Compounds↗
PubMed2001

[Palliation of urothelial carcinoma of the bladder].

Bladder cancer is a disease that occurs late in life (> 50% of the patients in Germany are 70 years or older). The general condition of the patients is frequently reduced, aggressive therapy of advanced tumours stages is therefore often contra-indicated. In this situation, palliative treatment is of extraordinary importance. Strangely enough, controlled prospective trials are lacking. They are, however, necessary in order to establish, or improve, standards of palliative treatment. Several smaller studies proved the potential of bladder irrigation and the embolisation of A. iliaca to stop bleeding from the tumourous bladder. If the tumour causes urinary retention, a permanent ureteral stent may in certain cases help to guarantee adequate flow. The assessment of palliative radiotherapy is not possible due to small numbers of (and highly selected) patients. It may have a potential in cases of hematuria, pain, and incontinence. New anti-tumour agents (e.g. Gemcitabine) may turn out to be a tolerable and effective palliative.

Aged↗
PubMed2006

The effects of low dose aluminum on hemorheological and hematological parameters in rats.

Aluminum (Al) is a nonessential element and humans are constantly exposed to Al as a result of an increase in industrialization and improving technology practices. Al toxicity can induce several clinical disorders such as neurotoxicity, gastrointestinal toxicity, hepatotoxicity, bone diseases, and anemia. This study aimed at evaluating the possible effects of short term and low dose Al exposure on hemorheological and hematological parameters in rats. Fourteen young, male Wistar albino rats were divided into two groups: 1 mg/200 g body weight of aluminum sulfate (Al(2)(SO(4))(3) was injected intraperitoneally to the first group for two weeks, three times a week. The animals of the control group received only physiological saline solution during this period. At the end of the experimental period, anticoagulated blood samples were collected and hematological parameters were determined using an electronic hematology analyzer. Red blood cell (RBC) deformability and aggregation were measured using an ektacytometer (LORCA) and plasma and whole blood viscosities were determined with a Wells-Brookfield cone-plate rotational viscometer. Significant decreases in mean corpuscular volume (MCV), red blood cell (RBC) deformability at low shear stress levels, the aggregation half time (t1/2) and the amplitude (AMP) of aggregation and significant increments in whole blood viscosity (WBV) at native and 40% hematocrit (Hct) of Al-treated rats have been observed. In conclusion, low dose Al(2)(SO(4))(3) exposure for a short-time may be responsible for alterations in either rheological properties of blood or hemorheological properties through a remarkable effect on RBC membrane mechanical properties . These alterations may also play an important role in the development of anemia in the Al-treated animals.

Alum Compounds↗
PubMed1998

Aluminum and acid effects on calcium and phosphorus metabolism in young growing chickens (Gallus gallus domesticus) and mallard ducks (Anas platyrhynchos).

Acidification is associated with increased mortality, reduced growth, and bone abnormalities in birds. Associated with acid deposition is an increase in aluminum availability due to solubilization from soil and other sources. (Conversely, experimental diets containing aluminum sulfate have much reduced pHs.) The present studies compare the effects of two levels of dietary acid (sulfuric acid) (0.122 and 0.56 mol H+ per kg feed; 0.056 and 0.277 mol sulfate per kg feed) and dietary aluminum (aluminum sulfate at 0.1 and 0.5%; sulfate at 0. 056 and 0.277 mol sulfate per kg feed) on bone growth, mineralization, and phosphorous/calcium homeostasis in growing birds (chickens and mallard ducks). Growth was reduced by the high acid (chicken) and aluminum (ducks and chickens) diets. A reduction in bone mineralization was observed in birds receiving aluminum-containing diets [low aluminum diet: decreased tibia ash, calcium, and phosphorus (chickens); high aluminum diet: decreased tibia dry weight, % of ash and mg; ash, calcium (chickens, ducks as % of ash), and phosphorus (chickens mg/duck, % of ash)]. Moreover, plasma concentrations of inorganic phosphate were reduced in chicks on the high aluminum diet. There were also marked decreases in bone growth and mineralization [tibia weight, ash (mg), calcium (mg), phosphorus (mg)] and plasma concentrations of 1,25-dihydroxy vitamin D3 in chicks on the high acid diet compared to those on a control diet. These changes were probably due to reduced feed intake; changes in bone indices being of a greater or similar magnitude in pairfed control. There was little change in bone indices, growth rate or feed consumption in ducklings receiving either the low or high acid diets. It is concluded that aluminum directly adversely affected bone mineralization whereas acid effects are mediated in part by changes in feed consumption.

Acids↗
PubMed2000

Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine.

In this study, we compared the immunogenicity and tumor-protective activity of anti-idiotypic antibodies mimicking a single tumor-associated epitope and tumor-associated antigen expressing multiple potentially immunogenic epitopes. We focused our study on the colorectal-carcinoma(CRC)-associated antigen GA733 (also known as CO17-1A/KS1-4/KSA/EpCAM). Monoclonal anti-idiotypic antibody (Ab2) BR3E4 was produced against murine anti-CRC mAb CO17-1A (Ab1) in rats. Full-length native GA733 protein was isolated from human tumor cells, and the extracellular domain protein (GA733-2E) was isolated from supernatants of recombinant baculovirus-infected insect cells by immunoaffinity chromatography. The immunomodulatory activity of the Ab2 was compared with that of the antigen, both in rabbits and in mice. Mice, like humans but not rabbits, express a GA733 antigen homologue on some of their normal tissues. Thus, these in vivo models allow the comparison of the immunogenicity of Ab2 and antigen in the presence (mice) and absence (rabbits) of normal tissue expression and immunological tolerance of the GA733 antigen homologue. In rabbits, aluminum-hydroxide(alum)-precipitated native GA733 antigen was superior to alum-precipitated Ab2 in inducing specific humoral immunity. In mice, alum-precipitated recombinant GA733-2E antigen, but not alum-precipitated Ab2, induced specific humoral immunity. However, when the Ab2 was administered to mice in Freund's complete adjuvant, specific humoral immune responses were elicited. Ab2 in complete Freund's adjuvant and GA733-2E in alum were compared for their capacity to induce antigen-specific cellular immunity in mice. Whereas lymphoproliferative responses were obtained with the recombinant antigen only, delayed-type hypersensitivity responses were obtained with both recombinant antigen and Ab2, although these responses were lower than after antigen immunization. The recombinant antigen in alum did not protect mice against challenge with antigen-positive syngeneic murine CRC cells. Similar studies with Ab2 BR3E4 mimicking the CO17-1A epitope were not possible because the tumor cells do not express this epitope after transfection with the human GA733-2 cDNA. However, similar studies with Ab2 mimicking the epitope defined by mAb GA733, which is expressed by the transfected tumor cells, indicated a lack of tumor-protective activity of this Ab2. In contrast, the full-length antigen expressed by recombinant adenovirus inhibited the growth of established tumors in mice. In conclusion, soluble antigen is a more potent modulator of humoral and cellular immune responses than Ab2, both administered in adjuvant. However, for induction of protective immunity, the immunogenicity of the antigen must be further enhanced, e.g., by expression of the antigen in a viral vector.

Adenocarcinoma↗
PubMed2000

Counterpoint. Cancer vaccines: single-epitope anti-idiotype vaccine versus multiple-epitope antigen vaccine.

Anti-idiotype (Id) vaccine therapy has been tested and shown to be effective, in several animal models, for triggering the immune system to induce specific and protective immunity against bacterial, viral and parasitic infections. The administration of anti-Id antibodies as surrogate tumor-associated antigens (TAA) also represents another potential application of the concept of the Id network. Limited experience in human trials using anti-Id to stimulate immunity against tumors has shown promising results. In this "counter-point" article, we discuss our own findings showing the potential of anti-Id antibody vaccines to be novel therapeutic approaches to various human cancers and also discuss where anti-Id vaccines may perform better than traditional multiple-epitope antigen vaccines.

Adjuvants, Immunologic↗