The immune systems of wild rats and of laboratory rats can been utilized as models of the human immune system in pre-industrial and post-industrial societies, respectively. In this study, lymphocyte phenotypes in wild rats were broadly characterized, and the results were compared to those obtained by us and by others using cells derived from various strains of laboratory rats. Although not expected, the production of regulatory T cells was not apparently different in wild rats compared to laboratory rats. On the other hand, differences in expression of markers involved in complement regulation, adhesion, signaling and maturation suggest increased complement regulation and decreased sensitivity in wild-caught rats compared to laboratory rats, and point toward complex differences between the maturation of T cells. The results potentially lend insight into the pathogenesis of post-industrial epidemics of allergy and autoimmune disease.
The standard of care for chronic gastro‐esophageal reflux disease (GERD), which affects up to 40% of the population, is the use of drugs such as proton pump inhibitors (PPIs) that block the production of stomach acid. Despite widespread use, the effects of PPIs on gastric fluid remain poorly characterized. In this study, gastric fluid was collected from patients undergoing cardiac surgery who were not (n = 40) or were (n = 25) actively taking PPIs. Various enzymatic and immunoassays as well as mass spectrometry were utilized to analyze the concentrations of bile, gastricsin, trypsin, and pepsin in the gastric fluid. Proteomic analyses by mass spectrometry suggested that degradation of trypsin at low pH might account, at least in part, for the observation that patients taking PPIs have a greater likelihood of having high concentrations of trypsin in their gastric fluid. In general, the concentrations of all analytes evaluated varied over several orders of magnitude, covering a minimum of a 2000‐fold range (gastricsin) and a maximum of a 1 × 106 –fold range (trypsin). Furthermore, the concentrations of various analytes were poorly correlated with one another in the samples. For example, trypsin and bile concentrations showed a significant (P < 0.0001) but not strong correlation (r = 0.54). Finally, direct assessment of bacterial concentrations by flow cytometry revealed that PPIs did not cause a profound increase in microbial load in the gastric fluid. These results further delineate the profound effects that PPI usage has on the physiology of the stomach.
Purpose: In the clinical setting, there is no reliable tool for diagnosing gastric aspiration. A potential way of diagnosing gastric fluid aspiration entails bronchoalveolar lavage (BAL) with subsequent examination of the BAL fluid for gastric fluid components that are exogenous to the lungs. The objective of this study was to determine the longevity of the gastric fluid components bile and trypsin in the lung, in order to provide an estimate of the time frame in which assessment of these components in the BAL might effectively be used as a measure of aspiration. Materials and Methods: Human gastric fluid (0.5 mg/kg) was infused in the right lung of intubated male Fischer 344 rats (n = 30). Animals were sacrificed at specified times following the experimentally induced aspiration, and bronchoalveolar lavage fluid (BALF) was collected. Bile concentrations were analyzed by an enzyme-linked chromatogenic method, and the concentration of trypsin was quantified using an ELISA. Data were analyzed using non-linear regression and a one-phase decay equation. Results: In this experimental model, the half-life of bile was 9.3 hours (r 2 = 0.81), and the half-life of trypsin was 9.0 hours (r 2 = 0.68). Conclusions:The half-lives of bile and trypsin in the rodent aspiration model suggest that the ability to detect aspiration may be limited to a few days post-aspiration. If studies using rats are any indication, it may be most effective to collect BAL samples within the first 24 hours of suspected aspiration events in order to detect aspiration.
Postindustrial society is plagued with pandemics of noninfectious, immune related illnesses. These diseases, which include allergic, autoimmune, and neuroinflammatory diseases, are not found in preindustrial societies, and are apparently caused by a limited number of environmental factors. These factors, essentially incompatible with human genetics, are each associated with a wide range of immune diseases. The most influential of these factors is a loss of diversity from the ecosystem of the human body, a condition termed "biome depletion." This state affects all postindustrial humans during and after fetal development, and remains the strongest challenge for modern medicine to overcome in the field of immunology. Fortunately, progress is being made. On the other hand, other factors associated with pandemics of allergic and autoimmune disease are within the control of each individual rather than the medical establishment. These factors include unrequited or chronic psychological stress, vitamin D deficiency, and substitution of breast milk with infant formula. Decreased breastfeeding in particular has a profound effect on immunity, probably through multiple mechanisms that involve increased stress levels, alterations of the human biome, and direct modulation of the immune system by mechanisms that remain largely uncharacterized. Given the synergism of these factors that adversely affect immunity in postindustrial culture, the importance of avoiding as many of these factors as possible is emphasized.
Background: Not only do infant formulas lack nutritional components supplied in breast milk, they lack a variety of maternal immune components normally transferred through breast milk, including microbial agglutinins. Bacterial aggregation by these agglutinins potentially reduces the likelihood of infection and is a critical step in the formation of the normal ecosystem of the infant’s gut, which is vital to proper immune system development. Objective: Given the need for better sources of breast milk for children who cannot receive their own mother’s milk, the effect of High Temperature, Short Time (HTST) pasteurization and Holder pasteurization methods on agglutinins in human breast milk was assessed. Methods: For this purpose, a small scale HTST pasteurization apparatus and protocol was created and validated. Bacterial aggregation was assessed indirectly by measuring initial changes in CFUs following post-pasteurization addition of exogenous bacteria, with less increase in CFUs being indicative of aggregation. Results: Raw milk and Holder pasteurized milk resulted in the fewest CFUs, with no difference observed between the two preparations. Interestingly, HTST pasteurized breast milk did not result in fewer CFUs than Holder pasteurized milk (p = 0.03), suggesting that the Holder method of pasteurization is at least as effective as HTST pasteurization at preserving bacterial agglutinins in human breast milk. Conclusion: Although more CFUs were observed in the assay using boiled human breast milk than any other milk preparation, the most CFUs were observed with infant formula, suggesting a propensity for that material to support uncontrolled planktonic bacterial growth.
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