Dan E. Berkowitz, MD

• Professor, Department of Anesthesiology and Critical Care Medicine
• Professor, Department of Biomedical Engineering
• Johns Hopkins Medicine
• Baltimore, Maryland

In recent years hiv infection elderly discount 800mg zovirax mastercard, the relationship between vitamin K and chronic diseases hiv infection rates 2014 order zovirax 400mg online, such as osteoporosis hiv infection of dendritic cells quality 200 mg zovirax, cardiovascular disease hiv infection detection purchase 800 mg zovirax free shipping, and cancer, and the possible health roles of osteocalcin and matrix Gla protein has become a topic of interest for researchers (Booth, 2009). These recommendations are generally presented as adequate intake or estimated values, and no tolerable upper intake level has been established for vitamin K (Walther et al. A common 2-methyl-1,4-naphtoquinone ring, also known as menadione or vitamin K3, characterizes all compounds with vitamin K activity. The chain length generally ranges from 4 to 13 prenyl units depending Effect of Fermentation on Vitamin Content in Food Chapter 7 139 on the organism by which the chain is synthesized. To complicate the picture, some bacteria produce isoprenologues with one or more unsaturated prenyl units. First, the naphthoquinone ring is synthesized from chorismate, a product of the shikimate pathway. The large variation in these values between the databases may be due to various reasons. For the data from the Turkish database, no further information is available concerning the precise definition of vitamin K2. These results were amended by recent published data on quantitative measurement of vitamin K in various fermented dairy products by Manoury et al. Until now, no data about the stability and changes in vitamin K concentrations during ripening of cheese and other fermented food have been available. The investigation of the bioavailability and bioactivity of vitamin K is in its infancy, and the results are still fragmentary. A large study that measured vitamin K2 concentrations in 62 fermented dairy products confirmed earlier findings that thermophilic species, such as S. These results were observed in a pH-controlled fermentation in which the decrease in pH to 5. Plants and microorganisms synthesize riboflavin unlike animals and humans who have to consume this essential nutrient with their diet. The most important sources for humans are milk and dairy products, fresh meat, liver, leafy vegetables, whole grains, and egg whites. Riboflavin is involved in supporting the immune and nervous system, forming red blood cells, producing cells, and activating folate and pyridoxine. Consequently, riboflavin deficiency is associated with increased lipid peroxidation. Riboflavin deficiency is mostly related to other B-vitamin deficiencies and manifests in various symptoms, such as stomatitis including painful red tongue with sore throat, chapped and fissured lips (cheilosis), and inflammation of the corners of the mouth. Additional signs of deficiency are itchy, watery and red eyes, sensitivity to light and dermatitis, corneal vascularization, anemia, and brain dysfunction (Rivlin, 2006). In 1970, van Veen and Steinkraus reported an increase of riboflavin in fermented food that was confirmed in 1984 by Murdock and Fields, who observed that the riboflavin content in fermented cornmeal was increased compared to the unfermented control. Similar results were produced in the fermentation of soybeans to tempeh and the fermentation of lentils, black gram, and rice by Rhizopus species and Klebsiella pneumonia, respectively (Ghosh and Chattopadhyay, 2011; van der Riet et al. In fermented dairy products, the riboflavin level can vary depending on the processing technology and the microorganisms utilized for fermentation. Whereas some yogurt starter cultures decrease riboflavin concentrations, others significantly increase the level of this vitamin compared to unfermented milk (Gulko and Kruglova, 1966; LeBlanc et al. In the past 15 years, biotechnological processes have replaced the traditional production of riboflavin with chemical processes (Stahmann et al. The screening of strains for riboflavin production resulted in a considerable number of species, such as B. Among them, Lactobacilli, Leuconostoc, Lactococci, and Propionibacterium were the most promising. The Lactococcus species led to an approximately two- and threefold increase in vitamin B2 content in sourdough bread and a diet supplemented with L. Vitamin B12 is the name used for several corrinoids that have the biological activity of cyanocobalamin. The vitamin is water soluble and sensitive to light as well as to oxidizing and reducing agents. Vitamin B12 is exclusively synthesized by microorganisms and is naturally found predominantly in animal-based food (meat, milk, fish, and eggs) but not in plant food. The main deficiency syndrome of vitamin B12 is pernicious anemia, which is characterized by the two primary symptoms megaloblastic anemia and neuropathy (Gille and Schmid, 2014; Office of Dietary Supplements, 2011; Stahl and Heseker, 2007b). Several studies showed that fermentation of milk leads to decreased concentrations of vitamin B12. Alm (1982) documented vitamin B12 losses in all fermented products analyzed (buttermilk, yogurt, kefir, ropy milk, acidophilus milk, bifidus milk). Vitamin B12 concentration in yogurt decreased Effect of Fermentation on Vitamin Content in Food Chapter 7 151 progressively over an incubation period of 5 h (Reddy et al. In cheese, lower vitamin B12 levels compared to milk are mainly due to the removal of the whey fraction, whereas the fermentation with starter cultures does not significantly affect vitamin B12 content (Arkbage et al. Lactic acid fermentation of cornmeal produced significantly higher vitamin B12 concentrations compared to the nonfermented control (3. The following genera have been reported to produce vitamin B12: Aerobacter, Agrobacterium, Alcaligenes, Azotobacter, Bacillus, Clostridium, Corynebacterium, Flavobacterium, Micromonospora, Mycobacterium, Nocardia, Propionibacterium, Protaminobacter, Proteus, Pseudomonas, Rhizobium, Salmonella, Serratia, Streptomyces, Streptococcus, and Xanthomonas (Martens et al. The dairy Propionibacterium strains have long been known for their vitamin B12 production capacity. In Swiss-type cheeses, Propionibacteria are added for the characteristic flavor and eye formation. Furthermore, they have been used as adjunct cultures for increasing the vitamin B12 concentrations in several fermented foods, such as kefir (Van Wyk et al. Furthermore, several Propionibacterium strains were investigated for their vitamin B12 production capacity on a whey medium, and the amounts of vitamin B12 produced varied (Staniszewski and Kujawski, 2007). The latter demonstrates the bioavailability of the vitamin produced by this strain (LeBlanc et al. The differences found by the investigators may reflect variations in the metabolic activity of the fermenting microorganisms. During lactic acid fermentation of cornmeal up to 96 h, the concentration of several B vitamins was analyzed. At 24 h, significantly less thiamine and choline were contained in the fermented samples, but the concentrations were restored at later time points. Samples fermented for 96 h showed significantly increased concentrations of pantothenic acid (1. However, with a judicious selection of microbial species and cultivation conditions, concentrations of specific vitamins, such as riboflavin, vitamin B12, folate, and vitamin K can significantly and naturally be increased in fermented food. Genetic modification of microorganisms promises an additional increase in their vitaminsynthesizing capacity. Using fermentation to increase vitamin concentrations in food is a natural, cost-effective, and better accepted alternative to current vitamin fortification programs. Fermented foods with increased vitamin content may assist in covering the vitamin requirements in populations with unbalanced diets and thus contribute to improving human health. Studies on the Vitamin B12 Enrichment of Yoghurt Using Lactobacillus plantarum and Propionibacterium freudenreichii. Comparison of folate losses in soybean during the preparation of tempeh and soymilk. Retention of vitamin B12 during manufacture of six fermented dairy products using a validated radio protein-binding assay. A general method for selection of riboflavinoverproducing food grade micro-organisms. Effect of fermentation by pure and mixed cultures of Streptococcus thermophilus and Lactobacillus helveticus on isoflavone and B-vitamin content of a fermented soy beverage. Distribution of isoprenoid quinone structural types in bacteria and their taxonomic implication. Synthesis and utilisation of folate by yoghurt starter cultures and probiotic bacteria.

It also affects the control of asthma (Xu and Xia hiv infection cycle animation generic zovirax 800 mg with visa, 1999) and breathing (Kazemi and Hoop hiv infection rates gay vs. straight order zovirax 800 mg on line, 1991) hiv infection rates state zovirax 200 mg amex. It may even correlate with aggressiveness in patients with depression hiv infection without ejaculation discount zovirax 200mg on-line, mania, and alcoholism (Bjork et al. It regulates brain excitability acting like a "brake" during times of runaway stress. For example, a selected number of benzodiazepines have a tendency to bind strongly to the A1 subunit, while others bind to different A subunits. Wheat germ Barley bran Foxtail millet Brown rice by proteolytic hydrolysis Glutinous brown rice (laozao) Diary products Cheese with L. Lactis as starter Cheddar cheese with probiotic strain Spanish artisanal cheese Fermented milk from Tibet Fermented milk Fermented milk Fermented milk 320 6773. The culture medium included rice bran, sugar as a carbon source, and yeast extract as a nitrogen source. However, there is a common propensity to believe that these molecules are obtained mainly synthetically. For this reason, the most important factor in the short- to medium term is to examine natural sources and investigate the effective dose of functional compounds if added both in isolation and as they occur naturally in the food matrix. The tendency of consumers to promote and maintain their health has facilitated the advancement of functional food which is growing thanks to the combination of plausible science and consumer perception. Testing and validation is yet another important step in increasing the prospects for clinical trials of bioactive molecules. Elevated -aminobutyric acid levels attenuate the metabolic response to bilateral ischemia. The production of a new tempeh like fermented soybean containing a high level of - aminobutyric acid by anaerobic incubation with Rhizopus. Effects of culture conditions on -aminobutyric acid accumulation during germination of foxtail millet (Setaria italica L. Evaluation of - aminobutyric acid, phytate and antioxidant activity of tempeh like fermented oats (Avena sativa L. Effects of dietary glutamine and gamma-aminobutyric acid on meat colour, pH, composition, and water-holding characteristic in broilers under cyclic heat stress. Spanish cheese screening and selection of lactic acid bacteria with high gamma-aminobutyric acid production. Effect of a gamma-aminobutyric acid-enriched dairy product on the blood pressure of spontaneously hypertensive and normotensive Wistar-Kyoto rats. Antihypertensive effect of honey-based beverage containing fermented rice bran in spontaneously hypertensive rats. Glutamic acid and gamma-aminobutyric acid neurotransmitters in central control of breathing. Microbial and chemical properties of aji-no-susu, a traditional fermented fish with rice product in the Noto Peninsula, Japan. Antihypertensive effects of Lactobacillus-fermented milk orally administered to spontaneously hypertensive rats. Isolation of gamma-aminobutyricacid-producing bacteria and optimization of fermentative medium. Presence and variation of -aminobutyric acid and other free amino acids in cocoa beans from different geographical origins. Germinated brown rice extract shows a nutraceutical effect in the recovery of chronic alcohol-related symptoms. Effects of vegetable containing gamma-aminobutyric acid on the cardiac autonomic nervous system in healthy young people. A multistrategic approach in the development of sourdough bread targeted towards blood pressure reduction. Effect of cheese containing gamma-aminobutyric acid-producing acid lactic bacteria on blood pressure in men. Selection of -aminobutyric acid-producing lactic acid bacteria and their potential as probiotics for use as starter cultures in Thai fermented sausages (Nham). Gamma-aminobutyric acid, a potential tumor suppressor for small airway-derived lung adenocarcinoma. Production and characterization of kimchi with enhanced levels of gamma-aminobutyric acid. Accumulation of g-aminobutyric acid in nodulated soybean in response to drought stress. Synthesis of -aminobutyric acid by lactic acid bacteria isolated from a variety of Italian cheeses. Physicochemical and functional characteristics of a novel fermented pepper (Capsiccum annuum L. Establishment of an efficient fermentation system of gamma-aminobutyric acid by a lactic acid bacterium, Enterococcus avium G-15, isolated from carrot leaves. Effects of anti-hypertension and intestinal microflora of spontaneously hypertensive rats fed gamma aminobutyric acid-enriched Chingshey purple sweet potato fermented milk by lactic acid bacteria. Dietary gammaaminobutyric acid affects the brain protein synthesis rate in ovariectomized female rats. The osmolyte strategy of normal human keratinocytes in maintaining cell homeostasis. Gamma-aminobutyric acid improves oxidative stress and function of the thyroid in high-fat diet fed mice. Clinical observations on the control acute attack of deficiency-syndrome asthma with -aminobutyric acid. Stimulation of gamma-aminobutyric acid synthesis activity in brown rice by a chitosan/ Glugermination solution and calcium/calmodulin. This page intentionally left blank Chapter 6 Melatonin Synthesis in Fermented Foods M. These reductions have also been linked to insomnia in older patients (Leger et al. In order to distinguish them, it has been proposed that the 3-(N-acetylaminoethyl) group is designated as side chain A (A) and the methoxy group will be designated as side chain M (M). It is an amphiphilic molecule, which can freely cross-cell membranes and distribute to any aqueous or lipid compartment including the membranes, cytosol, nucleus, and mitochondria of cells (Tan et al. Most of these organs (except retina) may not synthesize melatonin in a circadian manner nor do they release melatonin into the blood in any significant amount (Reiter et al. Melatonin produced in other organs functions locally as an antioxidant, autocoid, or paracoid to regulate intracellular events (Claustrat et al. These chemical properties of melatonin are relevant in food product formulations when exogenous melatonin is added to increase its content in them. They are involved among other things in modulating circadian rhythms, constricting and dilating blood vessels, reproductive regulation, and immuno-responsiveness (Witt-Enderby et al. Nevertheless, data are still incomplete in humans; more studies must be performed in much larger groups for longer periods. Theories and hypotheses of aging include damage by free radicals, especially in conjunction with mitochondrial dysfunction and/or inflammatory processes ("inflamm-aging") (Boren and Gershwin, 2004; Cevenini et al. These effects result from its direct free-radicalscavenger activity, indirect antioxidant properties, and antiinflammatory actions (Reiter et al. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition (Rosales-Corral et al. Thus this bioactive compound could be used in bone-grafting procedures, in reversing bone loss due to osteopenia and osteoporosis, and in managing periodontal disease. The content varies considerably not only between species but also among varieties of the same species and in the different organs of a given plant, usually ranging from pg/g to g/g of tissue. Microorganisms use tryptophan and their metabolites, such as indolacetic acid, tryptophol, or biogenic amines, as a nitrogen source.

Some of the treatments led to decreased expression of Cyp11a1 neem antiviral buy zovirax 200mg on-line, Hsd3b1 most common hiv infection symptoms 400 mg zovirax fast delivery, Cyp17a1 hiv infection statistics 2014 generic zovirax 400 mg overnight delivery, Hsd17b1 hiv infection rates by gender purchase zovirax 800 mg with amex, and Cyp19a1 compared to controls. Corresponding to differential dose responses for changes in gene expression, changes in hormone levels followed different patterns. Further, the mixture at 100 g/ml increased testosterone 4-fold and the mixture at 500 g/ml increased testosterone over 10-fold compared to controls. The mixture at 100 g/ml also increased progesterone over 10-fold and the mixture at 500 g/ml increased progesterone over 2-fold compared to controls. Collectively, these data suggest that the phthalate metabolite mixture impacts ovarian expression of key genes and hormones in the sex steroid hormone synthesis pathway. Flaws Phthalates are environmental toxicants that humans are exposed to daily because they are found in common consumer products. This is a public health concern because phthalates have been shown to disrupt ovarian function; yet little is known about their effects on ovulation, especially in humans. This is alarming because ovulatory defects are the leading cause of female infertility. Flaws Phthalates are chemicals used as plasticizers, which increase flexibility of polyvinyl chloride plastics. However, phthalates are non-covalently bound to plastic, thus causing them to leach. Phthalates are linked to health problems such as infertility due to interference with hormones and have been shown to affect preimplantation embryo development. Studies have shown that exposure to a single phthalate effects embryo development. Phthalates are used as solvents and plasticizers in a wide variety of consumer products. Most people are exposed to phthalates as parent compounds through ingestion, inhalation, and dermal contact. However, these parent compounds are quickly metabolized to more active compounds in several tissues. Although studies indicate that the phthalate metabolites reach the ovary, little is known about whether they are ovarian toxicants. Mice were euthanized in diestrus immediately following dosing or three or six months post-dosing. Estradiol, progesterone, and testosterone were analyzed in sera via enzyme-linked immunosorbent assays. A cohort of mice were bred immediately post-dosing and at three and six months post-dosing. Male reproductive dysfunction is a growing concern in the United States and beyond. This study aimed to mimic human exposure to phthalates, using mice as the model, by prenatally exposing male mice to an environmentally relevant mixture of phthalates. If anti-androgenic effects are induced by the exposure to the phthalate mixture, a decrease in testosterone in the circulating blood was expected. Testicular histopathology showed increased abnormalities in the phthalate mixture treated mice but not in the controls. Collectively, the data showed that prenatal exposure to the phthalate mixture decreased circulating testosterone levels in the male mice, indicating similar impact of phthalate mixture exposure to human gonadal dysfunction. Phthalates are used in a large variety of many consumer products, including personal care products and plastic containers. Previous studies have mainly focused on single phthalate exposure, however, humans are exposed daily to mixtures of chemicals, including phthalates. Previously, our laboratory developed a phthalate mixture made of 35% diethyl phthalate, 21% di(2-ethylhexyl) phthalate, 15% dibutyl phthalate, 15% diisononyl phthalate, 8% diisobutyl phthalate, and 5% benzylbutyl phthalate that mimics human exposure. We tested the effects of prenatal exposure to this mixture in the F1, F2, and F3 generations of female mice and found that it impaired reproductive outcomes in multiple generations. Impaired reproductive outcomes could be due to abnormal sex steroid, peptide, and gonadotropin hormone levels. However, it is not known whether the phthalate mixture affects these hormones in females. Thus, we tested the hypothesis that prenatal exposure to a phthalate mixture alters hormones in a multi- and transgenerational manner in female mice. Adult F1 females born to these dams were used to generate the F2 generation by mating them with unexposed males and adult F2 females were used to generate the F3 generation by mating them with unexposed males. Overall, these data suggest that prenatal exposure to an environmentally relevant phthalate mixture induces multi- and transgenerational effects on hormone levels in female mice. Males and females are genetically different mainly in their sex chromosome complement, leading to sexual dimorphisms. F1 males and females were bred with unexposed proven breeders to produce F2 generation males and females, respectively. When these F3 males of different lineages reached the age of 15 months, the reproductive indices were examined. Compared to controls, paternal lineage F3 males had lower serum testosterone levels, fewer sperms in the cauda epididymis, and fewer motile sperms. Their testes exhibited a morphologically distinguishable degeneration such as sloughed germ cells, failure of spermiation, and abnormal residual bodies. The F3 maternal lineage males also had lower serum testosterone levels, fewer sperm in the cauda, and fewer motile sperms but at lesser impact than those in the paternal line. Therefore, the next step is to explore the epigenetic differences in Y-chromosome that lead to this diverse transgenerational transmission between maternal and paternal lineages. F1 females were mated with untreated males to obtain the F2 generation, and F2 females were mated with untreated males to produce the F3 generation. Further, it dysregulated expression of cell cycle regulators and steroid hormone receptors. Phthalate exposure in women has been associated with decreased oocyte retrieval during in vitro fertilization protocols and greater incidence of early pregnancy loss. Oviducts from each animal were collected at 24 hours post-breeding and embryos recovered (n = 13-51 embryos per mouse) were subjected to microscopical examination to determine fertilization status. Animal studies show that they disrupt ovarian development, reduce fertility and promote reproductive diseases in females. Uteri of F1, F2 and F3 female offspring (n=6-8/group) were collected, weighed, and processed for histological evaluation at 12 month. Number of glands, size of endometrium and thickness of myometrial layers were similar in F1, F2 or F3 mice. Gland nests, large dilated glands and areas of epithelial hyperplasia were more prevalent in treated mice. These changes are linked to uterine pathologies such as endometritis and cystic hyperplasia in women. These effects may be exacerbated in women that become pregnant at advanced ages due to reduction in the number of oocytes undergoing maturation, evidenced by the extrusion of first polar body. Cryptorchidism, the most common male congenital abnormality, is variably associated with hypospadia, impairment of spermatogenesis and testicular germ cell tumors. Surgical relocation of the testes to the scrotum, orchiopexy, is performed to prevent these effects. Our hypothesis is that experimental surgical cryptorchidism could enhance testicular susceptibility to exogenous chemicals. Pregnant dams, F1 litters and F1 males were exposed to the chemicals by gavage, through milk, and by diet, respectively. The seminiferous tubules were scored according to the severity of the lesions with, the controls being 1. However, several of these non-occupational studies also showed no significant effects on spermatogenesis.

We designed an in vivo thrombogenicity assay for a dual lumen aortic cannula hiv infection rate in tanzania buy generic zovirax 800mg, the CardioGard Emboli Protection Cannula-Gen 2 hiv infected macrophages buy zovirax 200 mg without prescription, a device specifically designed for use in cardiopulmonary bypass antiviral foods list buy cheap zovirax 400mg. Differential blood flow rates through the dual lumens of the cannula is a feature in the clinical use of the device and were also deemed critical when simulating clinical use hiv symptoms immediately after infection zovirax 200 mg on line. After thoracotomy, each animal was placed on cardiopulmonary bypass using the CardioGard as the arterial supply cannula. Once each animal was successfully implanted, the heart was arrested and bypass was maintained for 6 hours with a flow rate of 5 L/min outlet and 1 L/min inlet. At the conclusion of the bypass duration, the animals were euthanized and the devices were removed for visual scoring of surface thrombus. Semi-quantitative thrombus assessment was performed by visual inspection of the CardioGard cannula and the lumen of the adjacent ascending aorta. The CardioGard return line filter was also visually assessed for thrombus deposition. All evaluated device surfaces and filters had no formed thrombus and scored "0" for thrombogenicity (no visible surface thrombus deposition). All device surfaces that were visually assessed for thrombus formation had no deposition evident. There was also no evidence of thromboembolism in the brain, kidneys and liver when examined grossly. The most interesting result to confirm the impairment of the barrier after 1h and up to the final readout of 24h has been the biotin assay that has shown a significant increase of biotin quantified by immunofluorescent detection related to the increased barrier permeability also confirmed by H&E staining. After review of the general scientific and toxicological merit of the Sauron et al. Tobacco products as well as nicotine containing replacements contain relatively high levels of nicotine. Research investigating the toxic potential of nicotine has to a large extent focused on interaction with nicotinic cholinergic receptors. The latter could be due to the reported lysosomotropic property of nicotine that may impair lysosome function. Simultaneous buildup of cellular damaged cellular molecules may explain the increased toxicity. Delivery of aerosolized medication to the lung assumes a mixing volume based on simple measures of inhaled volume. However, using a Chemical Engineering approach for evaluating stirred reactor vessels, it is possible to measure the actual volume involved in the mixing of an aerosol bolus. In theory, the actual volume should inform delivery of aerosolized medication to better calculate dose and, the dose of aerosolized medication should penetrate into the lung to a volume equivalent to the inhaled volume. However, in the case of airway obstruction it is not uncommon to supplement aerosol delivery with Heliox to achieve greater penetration into partially obstructed areas. Thus, a measure of penetration might, additionally, quantitatively inform treatment by providing a measure of penetration. Physician-scheduled pulmonary function testing were offered the opportunity through informed consent to perform aerosol dispersion testing. Concentration and volume data were fit to a previously tested sequential series stirred reactor vessel equation. The solution to the equation provided two parameters defined as the equivalent mixing volume and as the mixing coefficient or Peclet number. The ratio of the two parameters can also be used to delineate asthmatic subjects from asymptomatic subjects (p<0. Asthmatic patients displayed a range of equivalent mixing volume values between 25 and 100% of the one liter tidal volume. Those with the lowest percent predicted values for spirometry as seen in subjects with fixed airflow obstruction, were also the most likely to have lower equivalent mixing volumes. As a general trend, the equivalent mixing volume appears to increase with smoking exposure whereas it decreases with asthma. This indicates that there is a need for methods to evaluate increased penetration of nebulized medication in patients with obstructive airway lung diseases. Goering Additive manufacturing, otherwise known as 3D printing, research has become exceedingly popular in the recent years. According to a recent Reuters news report, 3D printing has provided new applications for medical imaging-based anatomical surgical models and medical devices. While 3D printing is becoming relevant in medical devices, a variety of factors can affect the biocompatibility of a medical device. Chemical characterization of medical device extractables by mass spectrometric techniques has emerged as a more selective alternative to traditional biocompatibility testing of medical devices, which utilizes biological test systems. The aim was to determine whether the extractables profile would be altered by 3D printing and thereby potentially affect the biocompatibility. Materials tested included the filaments prior to printing, a 3D printed cast for each filament, and a post processed 3D printed cast made from the PushPlastic filament. Sample extraction was performed with 3 different solvents (water, isopropyl alcohol and hexane) at 50oC for 24h with gentle agitation. Prints made of M30i filament showed fewer unique identified extractables than the prints made of PushPlastic filament based on the volatile extractables from hexane and isopropanol extractions. Further, the finished PushPlastic 3D print contained fewer identified compounds than the unfinished PushPlastic 3D print. Bioabsorbable polymers such as poly(lactic acid), poly(glycolic acid), and poly(lactic-co-glycolic acid) are widely used in medical devices. Although lactic acid and glycolic acid, the final degradation products, are biological compounds found naturally in the human body, high concentrations in the local microenvironment may result in adverse biological effects. The goal of this study was to evaluate the effects of different concentrations of lactic acid and glycolic acid as well as changes in pH on cellular responses and hemocompatibility. Hemocompatibility was evaluated using in vitro assays for hemolysis, coagulation cascade activation, and platelet activation/aggregation. For coagulation cascade activation, pooled human plasma was treated and assessed using the non-activated partial thromboplastin time assay. Finally, platelet aggregation and platelet activation were analyzed after exposure of human platelet rich plasma (200K platelets/L; 1 U/mL heparin) to lactic acid and glycolic acid. Platelet aggregation was analyzed by platelet count using an automated cell counter. Adverse blood responses including hemolysis, platelet activation, platelet aggregation, and coagulation were also observed after treatment with certain concentrations of lactic acid and glycolic acid. These results suggest that high concentrations of polymer degradants in the local microenvironment may result in adverse biological responses. After testing 42 chemicals, we correctly identified 93% of the Category 2A/B chemicals as Category 2. However, historically dogs on continuous infusion studies could not be exercised since they were surgically implanted with a permanent intravenous catheter. During the study, the dogs were disconnected from the pumps for 5x/week and allowed to exercise freely for 20 minutes/day before being reconnected to the pump. There were no incidents during the 20 minute daily exercise and no difficulties were encountered during the disconnection and reconnection of the infusion system prior to and after dog exercise. Also, we estimated the predictive capacity of the test method under the applicability domains. Meanwhile, eight chemicals were predicted as false-negatives, indicating the false-negative rate of 12. In addition, 21 chemicals were predicted as false-positives, indicating the false-positive rate of 40. Six of the eight false-negative chemicals were acidic, and one of the two non-acidic false-negative chemicals was a water-insoluble solid easily separated from a culture medium. Therefore, we examined to exclude 9 chemicals that have a pH level of 5 or less in test chemical solution and 3 solid chemicals that have both a logP value of 2. Under the applicability domain, false-negative rate, false-positive rate and accuracy were improved 2. Sulfur mustard, a chemical weapon used in World War I, the Iraq-Iran War, and in the 2015 Syrian conflict, is a vesicant that injures the eyes, lungs and skin. Ocular exposure leads to corneal microblistering, ulceration, and possibly loss of the corneal epithelium from its stroma, neovascularization, scarring, and a long term possibility of developing dry eye disease.

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