Integrative medicine最新文献

Epidemiological studies have found 2 significant factors associated with the increased incidence of autism spectrum disorder (ASD): the increased use of acetaminophen in the 1970s when this drug largely replaced the use of aspirin for many patients because of a fear of Reye syndrome, and the agricultural use in the 1990s of the herbicide glyphosate on crops that were genetically modified (GM) to tolerate glyphosate. The incidence of autism in the United States, where acetaminophen is widely available, is more than 1000 times greater than in Cuba, where acetaminophen is available only by prescription. Metabolites of both glyphosate and acetaminophen likely alter the function of the developmental protein sonic hedgehog (SHH). Glyphosate likely affects SHH indirectly by decreasing the beneficial flora of the gastrointestinal tract and increasing pathogenic Clostridia bacteria, which are resistant to glyphosate. The marked increase of certain Clostridia species caused by glyphosate results in Clostridia production of large amounts of 3-(3-hydroxyphenyl)-3-hydroxypropionate (HPHPA) and 4-cresol (p-cresol). The 4-cresol metabolite 4-methyl-o-hydroquinone and the acetaminophen metabolite N-acetyl-p-benzoquinone imine (NAPQI) likely react with the sulfhydryl group of the N-terminal cysteine of SHH, blocking the function of this critical amino acid required for the activation of SHH. HPHPA and 4-cresol also inhibit dopamine β-hydroxylase, resulting in overproduction of dopamine and its toxic metabolites, such as aminochrome, that cause biochemical damage to mitochondria and structural proteins in brain cells. Elevated amounts of these Clostridia products in body fluids in people with autism and in animals with autistic signs have been documented in laboratories throughout the world. The synthesis of the HPHPA molecule in extremely large quantities depletes the body of free coenzyme A, which is needed for the palmitoylation of SHH. SHH covalently coupled to palmitic acid is 30 times more active than SHH without palmitic acid. These possible modifications of SHH help to explain the significantly altered quantities of SHH in the blood serum of patients with autism. The severity of autism is related to the degree of SHH abnormality. The spread of pathogenic Clostridia worldwide from soil to food animals to humans, which may be promoted by glyphosate use, is a great public health concern, not only for autism but perhaps for all the neuropsychiatric diseases that appear to be related to gastrointestinal Clostridia overgrowth These diseases include seizures, tremors, tic disorders, Parkinson disease, chronic fatigue syndrome, obsessive compulsive disorder, schizophrenia, bipolar and unipolar depression, ADHD, and anorexia nervosa.

Chronic low-level arsenic exposure is a significant contributor to ill health and disease. However, at this time, quantification of the effects of this exposure appears virtually impossible. In a continuation of my editorial on arsenic published earlier this year, this editorial looks at arsenic's mechanisms of damage, more disease correlations, sources of exposure, and early signs for detection of arsenic toxicity.

Context: No organ system better integrates interconnectivity across specialties and disciplines than the microbiome. Scientific focus is shifting from microbes as harbingers of disease toward microbes as symbiotic, balanced, commensal ecologies.

Objective: The study intended to discuss and examine the human microbiome, including its development in early life; its impact on various physiological processes that occur throughout the body; and its relationship to dysbiosis; and to investigate microbial mechanisms with clinical applicability across medical specialties.

Setting: The study took place at Biocidin Botanicals in Watsonville CA, USA.

Results: Accumulating research upholds the human microbiome as both a predictive biomarker for disease risk and a viable treatment option for modulating the course of illness. Prebiotic and probiotic interventions continue to demonstrate clinical utility, particularly for gastrointestinal, dermatological, inflammatory, metabolic, and mental-health disorders.

Conclusions: Just as germ theory revolutionized infection control in the twentieth century, microbiome systems science stands to transform the conceptualization of health as the balanced coexistence of human and microbial cells in the twenty-first century.

This literature review explores the role of dietary oxalate in the development of chronic inflammatory kidney disease in middle-aged and older individuals. The authors pose the following questions: Is oxalate produced endogenously? If food sources contribute to chronic kidney disease and inflammation, what are those foods? What role do cultural food preparation and cooking play in denaturing food oxalates? The concentration of oxalates found within the body at any particular time is not limited to edible plants; normal human metabolic processes of breaking down ascorbic acid may create up to 30 mg of oxalate daily. Research supports urolithiasis as a common urologic disease in industrialized societies. Approximately 80% of kidney stones are composed of calcium oxalate, resulting in hyperoxaluria. Exogenous (originating outside the cell or organism) oxalate sources include ascorbic acid, amino acids, and glyoxal metabolism. Additional research estimates the daily endogenous (produced within the cell or organism) production of oxalate to be 10-25 mg. Suboptimal colonization of oxalate-degrading bacteria and malabsorptive disease are also contributing factors to the development of chronic kidney disease. Oxalate transcellular processes, though poorly understood, rely on multifunctional anion exchangers, and are currently being investigated. A review of research showed that normal human metabolic processes, including the breakdown of ascorbic acid, account for 35-55% of circulating oxalates and can create ≤30 mg of circulating serum oxalate daily. Glyoxylic acid accounts for 50-70% of circulating urinary oxalate in compromised individuals with liver glycation, bacterial insufficiencies, malabsorption, and anion exchange challenges. For persons with a family history of kidney stones, consumption of foods high in oxalates may be consumed in moderation, provided there is adequate calcium intake in the diet to decrease the absorption of oxalates from the meal ingested.

Tumor microenvironment infiltration by cells of the T helper cell type 1 (T_H1) system, including T_H1 cells, M1 macrophages, natural killer cells, and CD8⁺ T cells, is associated with better cancer prognosis. In contrast, tumor microenvironment infiltration by cells of the T_H2 system, including T_H2 cells, M2 macrophages, and innate lymphoid cells type 2, as well as immune suppressive myeloid-derived suppressor cells and regulatory T cells, is associated with poorer cancer prognosis. Beyond the tumor itself and a myriad of other modifying factors, such as genetic and epigenetic influences on tumorigenesis, the overall immune state of the patient, termed the macroenvironment, has also been shown to significantly influence cancer outcomes. Alterations in the tricarboxylic acid (TCA) cycle (TCA cycle breaks) involving loss of function of succinate dehydrogenase, isocitrate dehydrogenase, and fumarate hydratase have been shown to be associated with an intracellular metabolic shift away from oxidative phosphorylation and into glycolysis in cells that are transforming into cancer cells. The same loss of function of succinate dehydrogenase and isocitrate dehydrogenase has also been identified as inducing a shift in macrophages toward glycolysis that is associated with M1 macrophage polarization. M1 macrophages make interleukin 12, which stimulates T_H1 cells and natural killer cells to produce interferon gamma (IFN-γ), which in turn stimulates M1 macrophage activity, forming an activation loop. IFN-γ also drives activation of CD8⁺ T cells. Thus, M1 macrophage activation initiates and sustains activation of the T_H1 system of cells. In this fashion, TCA cycle breaks at succinate dehydrogenase and isocitrate dehydrogenase that promote cellular transformation into cancer cells are also associated with upregulation of the T_H1 system that provides anti-cancer immune surveillance. The T_H1 and T_H2 systems are known to inhibit each other's activation. It is this author's hypothesis that, in patients whose macroenvironment is sufficiently T_H2-dominant, the metabolic shift toward glycolysis induced by TCA cycle breaks that gives rise to mutagenic changes in tissue parenchymal cells is not counterbalanced by adequate activation of M1 macrophages, thus giving rise to cancer cell development. For instance, the atopic T_H2-high asthma phenotype, a T_H2 dominance-based comorbidity, is associated with a more than doubled incidence of colon, breast, lung, and prostate cancer, compared with non-asthmatics. Failure of TCA cycle breaks to induce M1 polarization of tissue-resident macrophages yields a tissue environment in which the tissue-resident macrophages fail to routinely perform M1-associated functions such as phagocytizing newly developing cancer cells. Failure of M1 phenotypic expression in both tissue-resident ma