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Wichita, KS, United States

Wagner S.C.,Batu Biologics | Markosian B.,Vaxenta Inc | Ajili N.,Batu Biologics | Dolan B.R.,Batu Biologics | And 8 more authors.
Journal of Translational Medicine | Year: 2014

Interleukin-2 (IL-2) therapy has been demonstrated to induce responses in 10-20% of advanced melanoma and renal cell carcinoma patients, which translates into durable remissions in up to half of the responsers. Unfortunately the use of IL-2 has been associated with severe toxicity and death. It has been previously observed and reported that IL-2 therapy causes a major drop in circulating levels of ascorbic acid (AA). The IL-2 induced toxicity shares many features with sepsis such as capillary leakage, systemic complement activation, and a relatively non-specific rise in inflammatory mediators such as TNF-alpha, C-reactive protein, and in advanced cases organ failure. Animal models and clinical studies have shown rapid depletion of AA in conditions of sepsis and amelioration associated with administration of AA (JTM 9:1-7, 2011). In contrast to other approaches to dealing with IL-2 toxicity, which may also interfere with therapeutic effects, AA possesses the added advantage of having direct antitumor activity through cytotoxic mechanisms and suppression of angiogenesis. Here we present a scientific rationale to support the assessment of intravenous AA as an adjuvant to decrease IL-2 mediated toxicity and possibly increase treatment efficacy. © 2014 Wagner et al.; licensee BioMed Central Ltd. Source


Background: Psychiatrists started using urine pyrroles (hydroxyhemopyrrolin-2-one, HPL) to diagnose psychiatric disorders many years ago. The biological origins of HPL are not known, nor are the causes of elevated urinary pyrrole excretion well understood. Methods: In the present study we analyzed the level of pyrroles in 148 patients with schizophrenia, 135 patients with bipolar disorder, 97 patients with depression, 119 patients with attention deficit hyperactivity disorder, and compared these data with the results of pyrrole tests for patients with non-psychiatric conditions and healthy volunteers. Results: According to our data, urinary pyrrole concentrations tended to be high in patients with psychiatric disorders, but elevated level of pyrroles was not specific for only these patients. We found evidence of an allergy related component in the fact that elevated pyrrole levels were significantly more prevalent in subjects with elevated histamine values. A role of intestinal bacteria, or imbalances in intestinal bacterial metabolism, was also suggested based on the found relationship between elevated pyrrole levels and elevations in indicans and urobilinogens. In addition, our data demonstrated that subjects with severely elevated pyrrole levels were deficient in nutrients such as zinc, Vitamin B3, and Vitamin C. Conclusion: Thus, pyrrole excretion seems to be a component of illness in general and not strictly psychiatric disorders. Source


Ichim T.E.,Riordan Clinic | Ichim T.E.,Medistem Inc | Minev B.,University of California at San Diego | Braciak T.,Medistem Inc | And 17 more authors.
Journal of Translational Medicine | Year: 2011

The history of ascorbic acid (AA) and cancer has been marked with controversy. Clinical studies evaluating AA in cancer outcome continue to the present day. However, the wealth of data suggesting that AA may be highly beneficial in addressing cancer-associated inflammation, particularly progression to systemic inflammatory response syndrome (SIRS) and multi organ failure (MOF), has been largely overlooked. Patients with advanced cancer are generally deficient in AA. Once these patients develop septic symptoms, a further decrease in ascorbic acid levels occurs. Given the known role of ascorbate in: a) maintaining endothelial and suppression of inflammatory markers; b) protection from sepsis in animal models; and c) direct antineoplastic effects, we propose the use of ascorbate as an adjuvant to existing modalities in the treatment and prevention of cancer-associated sepsis. © 2011 Ichim et al; licensee BioMed Central Ltd. Source


Gonzalez M.J.,University of Puerto Rico at San Juan | Miranda-Massari J.R.,University of Puerto Rico at San Juan | Duconge J.,University of Puerto Rico at San Juan | Allende-Vigo M.Z.,University of Puerto Rico at San Juan | And 14 more authors.
Puerto Rico Health Sciences Journal | Year: 2015

Human physiology depends on countless biochemical reactions, numerous of which are co-dependent and interrelated. The speed and level of completion of reactions usually depend on the availability of precursors and enzymes. The enzymatic activity depends on the bioavailability of micronutrient cofactors such as vitamins and minerals. In order to achieve a healthy physiological state, the organism requires that biochemical reactions occur at a controlled rate. To achieve this state it is required that metabolic reactions reach what can be considered an optimal metabolic equilibrium. A combination of genetic makeup, dietary patterns, trauma, disease, toxins, medications, and environmental stressors can elevate the demand for the nutrients needed to reach this optimal metabolic equilibrium. In this, part 1, the general concept of metabolic correction is presented with an elaboration explaining how this concept is increasing in importance as we become aware of the presence of genetic variants that affect enzymatic reactions causing metabolic disturbances that themselves favor or promote the disease state. In addition, part 1 reviews how prominent scientists have contributed in fundamental ways to our understanding of the importance of micronutrients in health and disease and in the development of the metabolic correction concept. © 2015 University of Puerto Rico. All rights reserved. Source


Mikirova N.A.,Riordan Clinic | Casciari J.J.,Riordan Clinic | Hunninghake R.E.,Riordan Clinic
Journal of Orthomolecular Medicine | Year: 2013

Background: Attention deficit hyperactivity disorder (ADHD) is characterized by atypically severe inattentiveness, hyperactivity, and impulsiveness. While its cause is unknown, biological and environmental influences are likely. Objectives: To identify the metabolic imbalances in fatty acid, amino acid, mineral, and pyrrole levels in ADHD patients, and to examine the effectiveness of the nutritional approach in the correction of these imbalances in an outpatient clinic. Design: Medical records of 116 patients with ADHD treated with nutritional approaches were retrospectively reviewed. Demographics were limited to ensure confidentiality. Blood levels of fatty acids, amino acids, vitamins and minerals, hair analysis of heavy metals and urine pyrrole levels were done on all patients. Comparisons with control (i.e., normal values) were made. Improvements following nutritional interventions were measured and compared to controls. Setting: The Riordan Clinic (Wichita, KS), an outpatient complementary and alternative medical clinic. Intervention: Various nutritional interventions (i.e., minerals, vitamins, omega-3 and omega-6 essential fatty acids, flavonoids, probiotics, dietary modifications and chelation of toxic metals by natural substances) were prescribed based on laboratory results. Main Outcome Measures: Serum fatty acid composition, measurements of minerals (normal and toxic) in hair and, in some cases, in red blood cells (RBC), and assessments of vitamins in serum and pyrroles in urine. Results: There was a predominance of below-normal docosahexaenoic acid, eicosapentaenoic acid, and gamma-linolenic acid levels; a high incidence of unfavorable arachidonic acid-to-eicosapentaenoic acid and omega-6-to-omega-3 ratios; deficiencies in zinc, magnesium, and selenium levels; and the presence of toxic metals in above-normal amounts. Conclusions: Our data suggests that at least two of the factors that were the most abnormal, omega-6-to-omega-3 ratios and pyrrole levels, and can in fact improve in subjects undergoing a regimen with nutrient supplementation. While nutritional manipulation did result in improved metabolic profiles in our sample, these results warrant a study of a larger sample, with an attempt to document whether these changes have an effect on improving behavior and cognition in the form of a prospective, controlled clinical study. Source

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