Aluminum-Induced Entropy in Biological Systems: Implications for Neurological Disease

Over the last 200 years, mining, smelting, and refining of aluminum (Al) in various forms have increasingly exposed living species to this naturally abundant metal. Because of its prevalence in the earth’s crust, prior to its recent uses it was regarded as inert and therefore harmless. However, Al is invariably toxic to living systems and has no known beneficial role in any biological systems. Humans are increasingly exposed to Al from food, water, medicinals, vaccines, and cosmetics, as well as from industrial occupational exposure. Al disrupts biological self-ordering, energy transduction, and signaling systems, thus increasing biosemiotic entropy. Beginning with the biophysics of water, disruption progresses through the macromolecules that are crucial to living processes (DNAs, RNAs, proteoglycans, and proteins). It injures cells, circuits, and subsystems and can cause catastrophic failures ending in death. Al forms toxic complexes with other elements, such as fluorine, and interacts negatively with mercury, lead, and glyphosate. Al negatively impacts the central nervous system in all species that have been studied, including humans. Because of the global impacts of Al on water dynamics and biosemiotic systems, CNS disorders in humans are sensitive indicators of the Al toxicants to which we are being exposed

Infusing Sodium Bicarbonate Suppresses Hydrogen Peroxide Accumulation and Superoxide Dismutase Activity in Hypoxic-Reoxygenated Newborn Piglets

The effectiveness of sodium bicarbonate (SB) has recently been questioned although it is often used to correct metabolic acidosis of neonates. The aim of the present study was to examine its effect on hemodynamic changes and hydrogen peroxide (H(2)O(2)) generation in the resuscitation of hypoxic newborn animals with severe acidosis.Newborn piglets were block-randomized into a sham-operated control group without hypoxia (n = 6) and two hypoxia-reoxygenation groups (2 h normocapnic alveolar hypoxia followed by 4 h room-air reoxygenation, n = 8/group). At 10 min after reoxygenation, piglets were given either i.v. SB (2 mEq/kg), or saline (hypoxia-reoxygenation controls) in a blinded, randomized fashion. Hemodynamic data and blood gas were collected at specific time points and cerebral cortical H(2)O(2) production was continuously monitored throughout experimental period. Plasma superoxide dismutase and catalase and brain tissue glutathione, superoxide dismutase, catalase, nitrotyrosine and lactate levels were assayed.Two hours of normocapnic alveolar hypoxia caused cardiogenic shock with metabolic acidosis (PH: 6.99 ± 0.07, HCO(3)(-): 8.5 ± 1.6 mmol/L). Upon resuscitation, systemic hemodynamics immediately recovered and then gradually deteriorated with normalization of acid-base imbalance over 4 h of reoxygenation. SB administration significantly enhanced the recovery of both pH and HCO(3-) recovery within the first hour of reoxygenation but did not cause any significant effect in the acid-base at 4 h of reoxygenation and the temporal hemodynamic changes. SB administration significantly suppressed the increase in H(2)O(2) accumulation in the brain with inhibition of superoxide dismutase, but not catalase, activity during hypoxia-reoxygenation as compared to those of saline-treated controls.Despite enhancing the normalization of acid-base imbalance, SB administration during resuscitation did not provide any beneficial effects on hemodynamic recovery in asphyxiated newborn piglets. SB treatment also reduced the H(2)O(2) accumulation in the cerebral cortex without significant effects on oxidative stress markers presumably by suppressing superoxide dismutase but not catalase activity

Die Lupine als Feldfrucht

von W. Kette, 9. Aufl

Die Lupine als Feldfrucht

von W. Kett

Fungal-specific humoral response in eosinophilic mucus chronic rhinosinusitis

Objectives/hypothesisAn immunoglobulin (Ig)E-mediated allergic pathogenesis is presumed in allergic fungal sinusitis (AFS), yet extensive polyps and eosinophilic mucus (EM) in the paranasal sinuses may also occur in the absence of allergy. Although a noninvasive fungal pathogenesis is presumed in all chronic rhinosinusitis with EM (EMCRS), fungal-specific nonallergic immune responses have not been thoroughly investigated. We tested the hypothesis that there is a fungal-specific humoral response in EMCRS and that it is not confined to IgE.Study designEMCRS patients were prospectively stratified into subgroups based on the presence or absence of fungi within EM and of fungal-specific systemic IgE. There were 12 AFS, 5 AFS-like, 8 nonallergic fungal eosinophilic sinusitis (NAFES), and 5 nonallergic, nonfungal eosinophilic sinusitis (NANFES) patients.MethodsAlternaria alternata and Aspergillus fumigatus-specific serum IgE, IgG, IgM, and IgA was measured by enzyme-linked immunosorbent assay and compared with strictly defined healthy and disease-control groups.ResultsFungal-specific IgG (Alternaria alternata P = .0002; Aspergillus fumigatus P = .004), and IgA levels (Alternaria alternata P = .0016; Aspergillus fumigatus P = .002) were higher in EMCRS compared with healthy volunteers but not with disease controls. Fungal-specific IgG3 levels were significantly elevated in all the EMCRS subgroups compared with controls for either fungal antigen (P ConclusionsFungal-specific immunity characterized by serum IgG3 and not IgE, distinguished the EMCRS subgroups from control groups regardless of the presence of fungus within EM or of systemic fungal allergy. Fungal-specific IgE responses in fungal-allergic EMCRS were no different to those in fungal-allergic controls, thus challenging the presumption of a unique pathogenic role of fungal allergy in "allergic fungal sinusitis."Pant, Harshita ; Kette, Frank E. ; Smith, William B. ; Wormald, Peter J. ; Macardle, Peter J

Clinical and laboratory characteristics of 19 patients with Churg-Strauss syndrome from a single South Australian centre

BACKGROUND: Churg-Strauss syndrome (CSS) is a rare, idiopathic systemic vasculitis. There is emerging evidence of an association between the presence or absence of antineutrophil cytoplasmic antibodies (ANCA) and clinical phenotype. Thromboembolism is an increasingly recognised complication of the disease. AIMS: Given the paucity of Australian data, the aim of this study was to examine the clinical and laboratory features of CSS in a single Australian centre. METHODS: We performed a retrospective review of all patients who fulfilled the American College of Rheumatology classification criteria for CSS managed at the Department of Immunology, Royal Adelaide Hospital between 2002 and 2008. RESULTS: Nineteen patients were included. All patients had asthma and most had upper airway involvement. Peripheral nerve, musculoskeletal, gastrointestinal and cutaneous involvement was common. Renal and cardiac involvement was uncommon in this series. Histological confirmation was obtained in 15 patients (78.9%). Ten patients (52.6%) were ANCA+, and these were more likely to have musculoskeletal involvement, such as arthralgia or myalgia (odds ratio 57, P = 0.005). Thrombosis was a feature at diagnosis in six patients (31.6%); two of these recurred with relapse. Sixteen patients (84.2%) were followed up; five died, and mean survival was 8.9 years. CONCLUSIONS: This is the first Australian study to focus on CSS. Our results demonstrate similar presentation and prognosis of CSS to previous descriptions; however, we noted that musculoskeletal involvement was more common in ANCA+ patients. In our series, thrombosis was a significant complication and we suggest that thromboprophylaxis may be warranted.A. F. Whyte, W. B. Smith, S. N. Sinkar, F. E. Kette, and P. Hissari

Nasal polyp cell populations and fungal-specific peripheral blood lymphocyte proliferation in allergic fungal sinusitis

Background: Allergic fungal sinusitis (AFS) is considered a different disease from other polypoid chronic rhinosinusitis diseases (CRS) with eosinophilic mucus (EM) termed eosinophilic mucus chronic rhinosinusitis (EMCRS). To substantiate this, studies on cellular responses to fungi and sinus mucosal inflammatory cell populations in AFS and other EMCRS diseases are required. This study was designed to examine polyp inflammatory cell populations and peripheral blood fungal-specific T-cell responses in AFS, other EMCRS subgroups (defined later), and polypoid CRS without EM. Methods: A prospective study was performed. Clinical characteristics, including CRS symptoms, sinus computed tomography (CT) scans, allergy status, intraoperative endoscopy, presence of EM, and fungal culture results were used to define patient groups. Polyps and peripheral blood were examined for populations of eosinophils, lymphocytes (CD4+, CD8+ T cells, natural killer cells, and B cells), and neutrophils using immunohistochemistry, cytospin preparations and flow cytometry. Fungal-specific peripheral blood lymphocyte proliferation was examined in AFS patients, other EMCRS patients, CRS patients, and controls. Results: There was no significant difference in the percentage of cell populations and fungal-specific lymphocyte proliferation between AFS and other EMCRS diseases. However, AFS and other EMCRS polyps had a higher percentage of eosinophils and CD8+ T cells whereas CRS polyps had higher CD4+ T cells. Fungal-specific lymphocyte proliferation was significantly greater in AFS and other EMCRS patients regardless of fungal allergy, whereas in CRS and controls, higher proliferation was observed in fungal-allergic individuals. Conclusion: These findings question the basis for differentiating AFS from other EMCRS diseases based on fungal allergy and fungi in EM. Fungal-specific cellular response was present in AFS and other EMCRS diseases, different from that associated with fungal allergy, suggesting a nonallergic fungal immune response. Increased CD8+ T cells in EMCRS polyps signify a different type of inflammation to CRS that may be driven by CD8+ T cells.Harshita Pant, Dimitra Beroukas, Frank E. Kette, William B. Smith, Peter J. Wormald, Peter J. Macardl