Establishing low-density lipoprotein apheresis tolerability in patients with prior anaphylactoid reactions to lipoprotein apheresis using magnesium sulfate.

BACKGROUND: Lipoprotein apheresis (LA) tolerability is a key factor for the utilization of this therapy. Common reactions to LA are hypotension and nausea. Serious reactions include severe hypotension and anaphylactoid reactions (0.13%-1.3% and 0.2%-0.4%, respectively). The bradykinin response drives these reactions and can worsen with the use of angiotensin-converting-enzyme inhibitors. Efforts to mitigate these reactions are necessary for the tolerability of LA with a dextran sulfate-adsorption (DSA) system. MATERIALS AND METHODS: In an effort to increase apheresis tolerability, seven patients at The University of Kansas, Department of Clinical Pharmacology, who had prior anaphylactoid reactions (defined as general cutaneous flushing, nausea/vomiting, tongue swelling, lightheadedness, and hypotension) to the DSA despite pharmacologic intervention, were treated with pre-LA intravenous magnesium adapted from a protocol developed by co-author Eliaz. This protocol consists of 1.5 g of magnesium sulfate administered over 45 minutes. All seven patients were treated with intravenous magnesium sulfate immediately before LA. RESULTS: No episodes of anaphylactoid reactions during LA have been reported to date. CONCLUSIONS: Magnesium infusion before DSA can be utilized to establish tolerability in patients with prior anaphylactoid reactions to LA. Proposed mechanisms include temporary stabilization of the negative-positive interactions of the dextran sulfate filter leading to a reduction of circulating bradykinin, reduction of nitric oxide, and reduction of the sympathetic response to LA.

Modified Citrus Pectin / Alginate Dietary Supplement Increased Fecal Excretion of Uranium: A Family.

CONTEXT: Uranium is found in geological deposits around the world. Toxicology of uranium includes nephrotoxicity, carcinogenicity, genotoxicity, diminished bone growth, and developmental defects. Mining and agricultural practices have escalated the regional exposure. OBJECTIVE: A family of six living in the Phoenix, AZ area had concerns about uranium exposure. For intervention, a dietary supplement of modified citrus pectin: sodium alginate (2:1) was recommended based on research supporting abilities to lower heavy metal toxicity. METHODS: Baseline urine and fecal samples were analyzed using inductively coupled plasma mass spectrometry. The supplement was self-administered at 3 capsules (750 mg/capsule) twice daily. Samples were taken at baseline, 6-days, and 6-weeks, additional fecal samples before stopping supplement and then after a 6-week washout period. Home water system was tested as well for heavy metals. RESULTS: Urine showed no detectable uranium whereas feces had significant change at 6-days, which persisted at 6-weeks. After a post-treatment period of 6-weeks, a decrease in excretion was seen in 5 of the 6 subjects. Home water showed cautionary levels of uranium. CONCLUSION: The supplement promoted fecal excretion of what is likely ongoing low-level exposure via ingestion. This is the first report of a supplement promoting uranium excretion suggesting it may reduce negative health effects in regions where chronic uranium exposure is known.

Improvements in Self-reported Lower Urinary Tract Symptoms With Prostate Health Supplement.

Context: Benign prostatic hyperplasia (BPH) produces lower urinary tract symptoms (LUTS) that diminish quality of life. Conventional treatments are often accompanied by adverse side effects. By contrast, consumers of phytochemicals-based dietary supplements often report a reduction in symptoms without side effects. The field needs studies that quantify the strength and character of perceived benefits. Objectives: The study intended to quantify the character and strength of perceived improvements in LUTS in men, after the consumption of a prostate health supplement. Design: The research team sent questionnaires to 200 potential participants, requesting their self-reported retrospective assessments of their LUTS for the month prior to starting their use of a prostate health supplement, ProstaCaid (ie, at baseline from memory), and their assessments at the time of the study (ie, postintervention) based on their current symptoms. Setting: The study was conducted from consumers of ProstaCaid at their home through a mailed questionnaire from Econugenics (Santa Rosa, CA, USA). Participants: Participants were 65 male patients, ages 56 to 86 y, including those diagnosed with BPH, prostate cancer, or multiple diagnoses, or who had no formal diagnosis. Interventions: Participants had taken at least 2 capsules/d of the supplement for a minimum of 2 mo. Outcome Measures: Participants were asked to recall and rate urinary tract symptoms: (1) incomplete emptying (ie, sensation of not emptying the bladder), (2) urinary frequency, (3) intermittency, (4) urgency, (5) weak stream, (6) straining, and (7) nocturia, (ie, how many times the participant typically gets up at night to urinate). A questionnaire based on the international prostate symptom score questionnaire was used. Logistic regressions, based on the proportional odds ratios of LUTS scores, were used for statistical analysis. Results: The participants reported substantial improvements in a range of individual and composite LUTS scores. In addition, the variability of current scores was substantially reduced compared with recalled, past scores, indicating that the perceived improvements were shared among the respondents. Statistical analysis identified urgency and weak stream as the symptoms showing the greatest reduction in perceived severity, which therefore could be used as the subject of future case-controlled studies. Conclusions: When properly interpreted, retrospective, self-reported data can yield insights into the perceived benefits of supplements and help guide the care of patients who augment traditional treatment with alternative medicines. Reported improvements can also guide the development of testable hypotheses for randomized, case-controlled studies.

Methods for the detection and serum depletion of porcine galectin-3.

BACKGROUND: Circulating galectin-3 (Gal-3) is elevated in systemic inflammatory disorders, fibrotic diseases, and in cancers. Gal-3 is a promising cancer target where it promotes tumorigenesis and metastasis, as well as in renal, pulmonary, hepatic, and cardiovascular diseases, because of its role as a driver of fibrotic remodeling. This reports goal was to establish methods for the detection and removal of porcine Gal-3 that will enable further studies of the therapeutic potential of Gal-3 depletion by apheresis in porcine disease models. The long-term aim is to develop a safe, effective method of removing Gal-3 via apheresis as a standalone therapeutic tool and as an adjuvant to other therapies. METHODS: Purified recombinant porcine Gal-3 was prepared and used as the standard for development of a porcine Gal-3 enzyme-linked immunosorbent assay (ELISA). Different affinity column matrices that incorporated either a rat IgG2a anti-Gal-3 monoclonal antibody or carbohydrate ligand were assessed for depletion of Gal-3 from porcine serum. RESULTS: A porcine Gal-3 ELISA with a linear range from 0.3 to 20 ng/mL was able to detect native porcine Gal-3 in both fetal (∼150-200 ng/mL) and juvenile (∼5-15 ng/mL) porcine serum samples. Use of an anti-Gal-3 monoclonal antibody affinity column depleted Gal-3 from porcine serum to at least 313 pg/mL, the limit of ELISA detection. CONCLUSIONS: Methods have been developed for the detection and depletion of porcine Gal-3. These methods will be used to study the specific effects of Gal-3 depletion via apheresis in porcine models of disease.

Activation of human T-helper/inducer cell, T-cytotoxic cell, B-cell, and natural killer (NK)-cells and induction of natural killer cell activity against K562 chronic myeloid leukemia cells with modified citrus pectin.

BACKGROUND: Modified citrus pectin (MCP) is known for its anti-cancer effects and its ability to be absorbed and circulated in the human body. In this report we tested the ability of MCP to induce the activation of human blood lymphocyte subsets like T, B and NK-cells. METHODS: MCP treated human blood samples were incubated with specific antibody combinations and analyzed in a flow cytometer using a 3-color protocol. To test functionality of the activated NK-cells, isolated normal lymphocytes were treated with increasing concentrations of MCP. Log-phase PKH26-labeled K562 leukemic cells were added to the lymphocytes and incubated for 4 h. The mixture was stained with FITC-labeled active form of caspase 3 antibody and analyzed by a 2-color flow cytometry protocol. The percentage of K562 cells positive for PKH26 and FITC were calculated as the dead cells induced by NK-cells. Monosaccharide analysis of the MCP was performed by high-performance anion-exchange chromatography with pulse amperometric detection (HPAEC-PAD). RESULTS: MCP activated T-cytotoxic cells and B-cell in a dose-dependent manner, and induced significant dose-dependent activation of NK-cells. MCP-activated NK-cells demonstrated functionality in inducing cancer cell death. MCP consisted of oligogalacturonic acids with some containing 4,5-unsaturated non-reducing ends. CONCLUSIONS: MCP has immunostimulatory properties in human blood samples, including the activation of functional NK cells against K562 leukemic cells in culture. Unsaturated oligogalacturonic acids appear to be the immunostimulatory carbohydrates in MCP.

The role of modified citrus pectin as an effective chelator of lead in children hospitalized with toxic lead levels.

CONTEXT: Lead toxicity is an ongoing concern worldwide, and children, the most vulnerable to the long-lasting effects of lead exposure, are in urgent need of a safe and effective heavy metal chelating agent to overcome the heavy metals and lead exposure challenges they face day to day. OBJECTIVE: This clinical study was performed to determine if the oral administration of modified citrus pectin (MCP) is effective at lowering lead toxicity in the blood of children between the ages of 5 and 12 years. METHOD: Hospitalized children with a blood serum level greater than 20 microg/dL, as measured by graphite furnace atomic absorption spectrometry (GFAAS), who had not received any form of chelating and/or detoxification medication for 3 months prior were given 15 g of MCP (PectaSol) in 3 divided dosages a day. Blood serum and 24-hour urine excretion collection GFAAS analysis were performed on day 0, day 14, day 21, and day 28. RESULT: This study showed a dramatic decrease in blood serum levels of lead (P = .0016; 161% average change) and a dramatic increase in 24-hour urine collection (P = .0007; 132% average change). CONCLUSION: The need for a gentle, safe heavy metal-chelating agent, especially for children with high environmental chronic exposure, is great. The dramatic results and no observed adverse effects in this pilot study along with previous reports of the safe and effective use of MCP in adults indicate that MCP could be such an agent. Further studies to confirm its benefits are justified.

Synergistic Antioxidant and Anti-Inflammatory Effects between Modified Citrus Pectin and Honokiol.

Inflammation is a normal physiological process; however, dysregulation of this process may contribute to inflammatory-based chronic disorders and diseases in animals and humans. Therefore, the antioxidant and anti-inflammatory properties of natural products, often recognized in traditional medicine systems, represent therapeutic modalities to reduce or prevent uncontrolled inflammatory processes which in turn potentially ameliorate or prevent sequelae of inflammatory-based symptoms of chronic diseases. We have investigated the antioxidant and anti-inflammatory effects of honokiol (HNK) and modified citrus pectin (MCP) in vitro and examined whether the MCP : HNK combination has synergistic effects on antioxidant and anti-inflammatory properties. Although both HNK and MCP induced a dose-dependent increase in antioxidant activity, the latter has a consistently higher antioxidant effect. The MCP : HNK (9 : 1) combination induced a synergistic effect on antioxidant activity suggesting that the combination is significantly more efficacious than individual compounds. In mouse monocytes, the lipopolysaccharide- (LPS-) induced tumor necrosis-α (TNF-α) synthesis was significantly inhibited by HNK and the MCP : HNK combination in a dose-dependent manner and synergistic effects were clearly demonstrated with the combination on TNF-α inhibition. This combination effect was also evident on inhibition of nuclear factor-kappa B activity, cyclooxygenase-II activity, and lipid peroxidation in mouse monocytes. Further research into the combination is warranted.

Integrative medicine and the role of modified citrus pectin/alginates in heavy metal chelation and detoxification--five case reports.

Heavy metal body burden can contribute to chronic disease, as well as interfere with the body's capacity to recover from illness. The five case studies presented here show that reduction in toxic heavy metals (74% average decrease) was achieved without side effects, with the use of PectaSol modified citrus pectin (MCP) (EcoNugenics; Santa Rosa, CA, USA) alone or with an MCP/alginates combination. The gradual decrease of total body heavy metal burden is believed to have played an important role in each patient's recovery and health maintenance. This is the first known documentation of evidence of such results in a clinical report of case studies with possible correlation between clinical outcome and a reduction in toxic heavy metal load in patients using MCP and/or an MCP/alginate complex.

Inhaled recombinant alpha 1-antitrypsin ameliorates cigarette smoke-induced emphysema in the mouse.

In alpha 1-antitrypsin deficiency in humans, inadequately regulated activity of serine protease activity is responsible for the chronic lung tissue degeneration and irreversible loss of pulmonary function seen in those individuals with emphysema. Typically, disease symptoms in this patient population are exacerbated by cigarette smoke. Here we show that inhaled recombinant alpha 1-antitrypsin (rAAT) can provide significant protection against the development of emphysema in cigarette smoke-treated mice. As has been reported previously, cigarette smoke was seen to increase significantly the recruitment of neutrophils and macrophages into the lungs of these animals, leading to concomitant alveolar airspace enlargement and emphysema. In smoking animals treated for 6 months with inhaled rAAT, effects on lavage levels of neutrophils and macrophages were only moderate when compared with untreated animals. Furthermore, neutralizing antibodies to rAAT were generated in all rAAT-treated animals. Despite this, however, reductions in airspace enlargement of up to 73% were observed. These findings demonstrate that delivery of rAAT directly to the lungs of smoke-treated mice can inhibit lung tissue damage mediated by proteases, suggesting that rAAT inhalation therapy might represent a practical approach towards treating emphysema in humans, by modifying the course of the disease.