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Encoded by the SERPINA1 gene (also known as PI) Highly pleomorphic with extensive allelic variation Disease manifestation associated with null variants or genotypes resulting in impaired gene expression, translation or protein synthesis Majority of individuals with lung or liver disease are homozygous for alleles Z or S or heterozygotes with one wild type and one S/Z allele These null variants cause abnormalities in the tertiary structure of molecule Protein synthesis in the rough endoplasmic reticulum (ER) of the hepatocyte is delayed Approximately 85% of molecules polymerize into large conglomerates Quality control systems recognize most mutant molecules as abnormal and shunt to proteolytic mechanisms leading to few non-polymerized molecules released into blood Antiproteolytic activity against neutrophil elastase reduced to 15-20% of normal serum levels leading to pulmonary damage Those polymers that cannot be further processed accumulate and form inclusions in the ER Triggers activation of variety of cellular responses Autophagy upregulation Mitochondrial damage Activation of apoptotic pathways Activation of ER stress pathways Eventually results in hepatocyte injury and death Increased risk of liver fibrosis and cirrhosis Amount of polymerized molecules correlate with stage of cirrhosis Likely that important environmental and genetic disease modifiers (as yet unknown) affect rate and magnitude of hepatocellular death Pathogenesis Annu Rev Pharmacol Toxicol 2005;45:605-28 Clin Liv Dis 2009;12:915-937 Eur J Gastroenterol Hepatol 2010;23:8-22 Lancet 2003;362:1819-27 Lancet 2008;371:838-51 Med Clin N Am 2009;93:787-799 NEJM 2008;358:2378-87 Gastroenterology 2008;134:16411654 N Engl J Med

Carbs/Sugars Meals containing high levels of carbohydrates and/or sugars can lead to abnormal gut flora by encouraging the growth of certain pathogens such as Candida

Protective effects of hydro-alcoholic extract of Quercus Brantii against lead-induced oxidative stress in the reproductive system of male mice

Vitamin B12 is a nutrient that helps keep your blood and nerve cells healthy

Lower doses use more water to enlarge the draw, as the table lists