ABSTRACT
The US Food and Drug Administration
(FDA) recently issued guidance intended to curtail the use of medically
important antibiotics in agricultural applications. In the wake of these
recommendations, the veterinary medicine community has mobilized to define and
commercialize effective alternative pathogen controls. In this article, we draw
attention to the scope of the challenge by highlighting some of the most
significant, pathogen-borne diseases relevant to food-producing animals. We
also review the antimicrobial properties intrinsic to midchain triglyceride
lipolysis products, and present the question: What is the untapped potential of
these safe-for-consumption, environmentally benign, and mechanistically
privileged antimicrobial natural products?
INTRODUCTION
“A definitive link
(exists) between the routine, nontherapeutic use of antibiotics in food animal
production and the crisis of antibiotic resistance in humans.”1 In
2012, as part of a campaign to reduce the selection pressure that drives the
advancement of antibiotic-resistant bacteria strains, the FDA issued Guidance
for Industry (GFI) #209, which aims to limit the agricultural use of antibiotics
that have important human therapeutic applications,2 and defines two
principles for judicious drug use in food-producing animals. Administration
should be (1) limited to those uses that are considered necessary for ensuring
animal health, and (2) limited to those uses that include veterinary oversight
or consultation. As a corollary, in 2013, the FDA published means for
voluntarily phasing out growth promotion indications for medically important antibiotics
in accordance with GFI #209.3 In line with these recommendations,
the veterinary health community is striving to bring alternative approaches for
mitigating pathogen-borne diseases to bear while maintaining the industry’s
ability to meet the nutritional demands of a growing global community.
Of course, finding
alternative means for preventing, treating, or controlling pathogen-borne diseases
in food-producing animals is no easy feat. Pathogenicity ties to a wide array
of bacteria (e.g., Gram-negative, Gram-positive, both), can manifest in myriad disorders,
and can impact every food-producing animal species. The permutations are daunting
and, as a result, comprehensive solutions will continue to be difficult, if not
impossible, to identify. The challenge is exacerbated by the fact that
antibiotic drug innovation has significantly lagged behind the pace of
resistance development.4,5 The following underscores some of the most
pressing indications relevant to different agricultural livestock. Midchain
triglycerides, in view of the antimicrobial properties of their lipolysis
products, are also discussed as a potentially untapped resource for protecting
the food supply and reducing the selection pressure that breeds microbe antibiotic
resistance.
UNDERSTANDING THE BREADTH OF THE CHALLENGE
Perhaps the best way to
communicate the scope of the selection pressure reduction/animal health
protection conundrum is to call attention to some of the challenges recently presented
in the open innovation forum. Stakeholders from the animal pharmaceutical
industry (e.g., Elanco) have recently issued requests for proposals relevant to
swine, poultry, and cattle health. The following case studies are by no means
comprehensive, but they do serve to illustrate the breadth of the challenge.
Case Study 1: Ruminant Mastitis
Ruminant mastitis is an
inflammatory reaction of udder tissue that is often attributable to bacterial
infection. It is the most prevalent disease in dairy cattle in the United
States, and is the costliest affliction for the dairy industry. Mastitis
accounts for losses of approximately $200 per year, per cow.6 If the
underlying infection persists unchecked, it can be fatal for the animal. Single
pathogens or combinations thereof can spur mastitis. The Gram-positive bacteria
staphylococci and streptococci are the most commonly observed causative
pathogens, but Gram-negative bacteria, such as E. coli, have also been observed
to cause the disease. Mycoplasma bovis is yet another pathogen of
increasing relevance as a cause of mastitis. Absent the ability to broadly
administer antibiotic mitigations for mastitis going forward – and in view of
the 20% infection rate (despite antibiotic regime implementation) – alternative
approaches are urgently needed for preventing, treating, or controlling mastitis
in dairy cattle and other ruminants.7,8
Case Study 2: Porcine Ileitis
Proliferative enteropathy
(PE, also known as ileitis) is one of the most prevalent and economically
detrimental diseases affecting the global swine industry.9 Ileitis
is caused by the bacterial pathogen, Lawsonia intracellularis.
The Gram-negative bacterium infects the enteral epithelial cells of the animal,
triggering hyperplasia and inflammation in the small and large intestines. To
illustrate its economic impact, a recent study of a 735 sample population found
an infection rate of 16.87%,10 and the cost to treat PE is estimated
at $2 to $3 per pig ($15 in severe cases).11 Vaccination, antibiotic
treatments, or combinations thereof are effective in the mitigation and
treatment of natural and clinically mediated outbreaks of ileitis in pigs.10
GFI #209 and GFI #213 may limit, however, the continued use of streptogramin
(eg, Virginiamycin), macrolide (eg, Tylosin), tetracycline (eg,
chlortetracycline) and fluoroquinoline (eg, Enrofloxacin) class treatment
options.11,12 Animal health stakeholders are therefore seeking to
bolster the available solution set, which presently includes Enterisol®
Ileitis vaccine and veterinary use-approved pleuromutilin class antibiotics
(eg, Tiamulin).13,14
Case Study 3: Necrotic Enteritis in Poultry
Gram-positive Clostridium
perfringens have been cited as one of the most common causes of food
poisoning in humans, often resulting from insufficient poultry and meat
cooking times and temperatures.15 In living food-producing
fowl, necrotic enteritis is one of the most prominent manifestations of
C. perfringens’ enterotoxins. The food safety implications,
higher rates of mortality, and stunted animal growth associated with
necrotic enteritis are estimated to cost the global poultry industry
more than $2 billion annually.16,17 Until recently, food-
and water-borne dispensation of antibiotics was adequate in keeping C.
perfringens’ pathogenicity at bay. Because some of the administered
classes of antibiotics saw shared use in human therapeutics, and
because some were used principally for growth promotion, this preventive
measure was discontinued. To meet the aspirations of GFI #209 and
GFI #213 and protect the health of this integral food-producing animal
category, new options are required to control the disease.
ANTIMICROBIAL LIPIDS’ RELEVANCE IN THE “POST-ANTIBIOTIC ERA”
The in vitro antimicrobial
and antiviral potential of fatty acids and monoglycerides has been extensively
documented in the primary and secondary scientific literature,18-20 with
the phenomenon first having been documented (in the modern scientific era) in
the late 19th century.21,22 Studies of the biological ramifications
of ingesting triglycerides comprising these fatty acids and monoglycerides,
however, are perhaps lesser known. For example, a series of inquiries
correlating certain dietary lipids and a reduced incidence of pathogen-borne
infectious diseases was the subject of unrelated research, which nevertheless
seeds a potential approach to mitigating antibiotic resistance.
STUDIES REVEALING LIPIDS’ ANTIMICROBIAL PROPERTIES SPUR
IMPORTANT QUESTIONS
The antibacterial
contribution of fatty acid triglycerides in human colostrum and milk, and the
mechanism by which these lipids realize their antibiotic potential, was defined
as part of a broader initiative to rationalize higher infection resistance
observed in breast-fed, versus bottle-fed, infants.23-26 In their
seminal 1978 publication, Welsh and May observed that the lipolysis products of
colostral lipids – in particular, monoglyceride and fatty acid fractions – were
implicit resistance factors in human milk.27-29 Isaacs and coworkers
further substantiated this finding, defining the role of endogenous lipases
(lingual and gastric) in unmasking milk triglycerides’ antimicrobial activity
in the gastric environment.30-32 Important contemporary research
conducted by Kabara et al significantly expanded the understanding of fatty
acid/monoglyceride structure-antimicrobial function relationships;33-37
the superior antibacterial potency of midchain acids and MAGs became clear. In
view of this work, Isaacs et al went on to compare the lipase-mediated
antiviral potential of infant formulas containing midchain triglycerides against
those exclusively containing long chain triglycerides. MCT-containing formulas exhibited
much more potent antimicrobial activity than those containing conventional dietary
lipids.38-40 These studies raise important questions as to whether
masked antimicrobial triglycerides (ie, midchain and particular structured
triglycerides) can meaningfully reduce the incidence of pathogen-borne enteric
diseases in agricultural animals.41
Is there an analogy to be
established with observations of reduced infection occurrence in human infants?
If the in vivo mechanism of coaxing certain lipid triglycerides’ antimicrobial
activity holds, the answer is likely “Yes.”
ANTIMICROBIAL LIPIDS DEMONSTRATE THE SCOPE TO ADDRESS GRAM-POSITIVE
& GRAM-NEGATIVE PATHOGENS
For a dietary or other
adjunctive therapeutic strategy to have true utility preventing, treating, or
controlling infections in animals, the antimicrobial lipids revealed during lipolysis
would need to demonstrate broad antimicrobial efficacy. Indeed, Gram-positive
and Gram-negative bacteria have both been shown to be susceptible to the
membrane disruptive characteristics of monoglycerides and free fatty acids.
Incidentally, midchain variants are the most frequently cited antimicrobial
agents. Table 1 highlights specific species of bacteria and the fatty acid and/or
monoglycerides that have been observed to inhibit their growth, in vitro.
Studies conducted by Kabara,33-37 Bergsson,42 and McGuire43
demonstrate that Gram-positive staphylococci and streptococci, the most
commonly implicated pathogens in bovine mastitis, succumb to the action of monoglycerides
and fatty acids. Petra,44 Thormar,49 and Bergsson50
have collectively shown that Gram-negative bacteria including E. coli, H.
pylori, various Campylobacter species, and P. aeruginosa are
vulnerable to monocaprin. These examples of Gram-negative bactericidal activity
bode well for enterally released MAGs’ and FFAs’ potential to control pathogens
responsible for ileitis and necrotic enteritis. As can be gleaned from Table 1,
triglyceride lipolysis products show a much broader range of antimicrobial activity
than is presently discussed.
NASCENT ANTIMICROBIAL MCT & STRUCTURED LIPIDS ARE PRACTICAL
IN USE
Examining the therapeutic
effectiveness of masked antimicrobial lipids represents, perhaps, a simpler
task than taking on other antibiotic attenuation strategies. Certainly, the scope
pales in comparison to that of developing new classes of antibiotics for animal
health applications and bringing them to market. To this point, MCTs (eg,
C7-C13 fatty acid triglycerides) and structured triglycerides (eg, glyceryl
tricaprylate/caprate/linoleate) have a well-established record of safe use in
human and animal nutrition applications (Figure 1). Additionally, there is
global precedence for the use of lipid-based excipients for enhanced drug
delivery in human and veterinary medicine. Implementation approaches for
liquid, semi-solid, and solid lipids have also been established, lending credence
to the feasibility of this unique application. Lipids can be administered in solid
feed formulations, in liquid feed formulations (eg, as dilute emulsions for
enteral use), and in formulations designed for modified, targeted and/or
controlled release. In the latter case, liposomal, solid lipid nanoparticle and
parenteral systems would come in to play. Antimicrobial lipid delivery
mechanisms, and the scope of antimicrobial activity of monoglycerides and fatty
acids themselves, have been very well reviewed in recent years.18-20
AGRICULTURAL APPLICATIONS OF ANTIMICROBIAL LIPIDS ARE ALREADY
UNDERWAY
Understanding the
antimicrobial potential of monoglycerides and fatty acids – and triglycerides
in conjunction with lipolytic enzymes – has, of course, spurred real-world application
pursuits. For example, Hilmarsson et al evaluated the effect of glycerol
monocaprate on broiler chickens that were deliberately, and naturally, exposed
to the Gram-negative bacterium C. jejuni.51 The viable
bacteria count in artificially contaminated water (initially, 6 log10
cfu) was observed to be reduced to undetectable levels upon treatment with
glycerol monocaprate emulsions (0.6% monocaprin). No infection was observed in chickens
provided treated water, and healthy growth was observed in the experimental group.
In a nod to the utility of MCTs as masked antimicrobials, Aurousseau et al in
1984 reported an observed 40% growth rate increase in preruminant calves that
were fed a glyceryl tricaproate- or tricaprylate-containing milk substitute
formulation, as compared with a formula containing tallow lipids alone.52
The antimicrobial activity of the C6/C8 fatty acids released by gastric lipases
in the gut rumen was cited as the principal rationale for the favorable growth outcomes.
Perhaps most importantly, Diereck and Decuypere in 2002 methodically
demonstrated the use of structured and midchain triglycerides in tandem with
lipolytic enzymes to favorably impact the gut flora of piglets.53,54
These studies reinforce the notion that enterally released fatty acids and
monoglycerides constitute a legitimate and effective approach to controlling
myriad enteric infections in food-producing animals.
ANTIMICROBIAL LIPIDS’ ALIGNMENT
WITH THE PRINCIPAL OF DOING NO HARM
Safe for Animal & Human Consumption
As previously mentioned,
midchain and structured triglycerides have a well-established record of safe
use in food, nutrition, and pharmaceutical applications – human and animal. It
should also be underscored that antimicrobial monoglycerides and fatty acids
(ie, triglyceride lipolysis products) are Generally Recognized as Safe (GRAS)
by the FDA per CFR § 184.1505 and CFR § 172.860, respectively.
Environmentally Friendly
Categorically, midchain
and structured triglycerides demonstrate ready biodegradability. This is a
function of the fact that they comprise hydrolytically unstable ester bonds,
and are composed of natural product fatty acids commonly encountered in the
environment and in a wide variety of biological systems.
No Exertion of Selection Pressure
The membrane disruption
mechanism underlying FFA and MAG antimicrobial properties42,50,55,56
does not contribute to the prevalence of antibiotic-resistant bacteria. These
species are not understood to invoke the reproductive or metabolic interference
mechanisms common to conventional antibiotic classes.
Scalability, Relevance
Midchain and structured
triglycerides can be manufactured in a cGMP environment, on scales suitable for
the agricultural animal health applications proposed herein.
SUMMARY
Organizations across the
food-producing animal industry are proactively doing their part to address the
specter of antibiotic resistance. Among them, the animal pharmaceutical industry
continues to grapple with how they will continue to enable farmers’ delivery
against the nutritional demands of a growing global community, while also
winding down the use of antibiotics of mutual importance in human therapeutics.
In this article, we have raised examples of focal point diseases that are
driving the search for viable pathogen control alternatives, and have raised the
important role that midchain and structured triglycerides can play in the effort.
REFERENCES
1. Clifford, J.; Khan, A.;
Sharfstein, J. Hearing before the House Committee on Energy and Commerce, Subcommittee
on Health. July 14, 2010. Antibiotic resistance and the use of antibiotics in animal
agriculture. The authors represented the U.S. Food & Drug Administration,
the U.S. Department of Agriculture, and the Centers for Disease Control and
Prevention.
2. U.S. Food & Drug
Administration. Guidance for Industry 213. December 2013. New Animal Drugs and
New Animal Drug Combination Products Administered in or on Medicated Feed or Drinking
Water of Food-Producing Animals: Recommendations for Drug Sponsors for
Voluntarily Aligning Product Use Conditions with GFI 209. http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEnforcement/GuidanceforIndustry/UCM299624.pdf.
(RetrievedDec. 12, 2016).
3. U.S. Food & Drug
Administration. Guidance forIndustry 209. April, 2012. The Judicious Use of Medically
Important Antimicrobial Drugs in Food-Producing Animals.
http://www.fda.gov/downloads/AnimalVeterinary/GuidanceComplianceEn
forcement/GuidanceforIndustry/UCM216936.pdf.
(Retrieved Dec. 12, 2016).
4. Cooper, M.A.; Shlaes, D.
Nature 2011, 472, 32. Fix the antibiotics pipeline.
5. Shlaes, D.M. et al.
Antimicrob. Agents Chemother. 2013, 57, 4605. The FDA reboot of antibiotic
development.
6. Department of Animal
Science. MacDonald Campus of McGill University. "Mastitis in Dairy
Cows" 2003. https://web.archive.org/web/2003070811370
2/http://animsci.agrenv.mcgill.ca/courses/450/topics/13.pdf.
(Retrieved December 27,2016).
7. Alternatives to antibiotics:
Prevention or treatment of food-producing animals. InnoCentive Challenge ID:
9933897. Waltham, MA: InnoCentive, Inc. Posted December 20, 2016. For an
additional example of important pathogen-precipitated cattle diseases, see
reference 8.
8. Elanco, Inc. Liver
Abscess formation in cattle. InnoCentive Challenge ID: 9933889. Waltham, MA:
InnoCentive, Inc. Posted November 17, 2016.
9. Kroll, J.J. et al. Animal
Health Res. Rev. 2005, 6, 173. Proliferative enteropathy: a global enteric disease
of pigs caused by Lawsonia Intracellularis.
10. Alberton, E.L. et al.
Acta Sci. Vet. 2011, 39, 943. Prevalence of porcine proliferative enteropathy associated
to Lawsonia intracellularis in pigs slaughtered in Mato Grosso State, Brazil.
11. Boehringer Ingelheim
Animal Health GmbH. Ileitis Technical Manual 3.0 2006, Ch. 6.2. Which antibiotics
are most effective against ileitis? http://www.thepigsite.com/publications/2/ileitis/93/62-which-antibiotics-are-mosteffective-against-ileitis/.
(Retrieved Dec. 13,2016).
12. Muirhead, M.R.;
Alexander, T.J.L. Managing Pig Health: A Reference for the Farm, 2nd Ed. Carr, J.
(ed.) 5M Publishing: United Kingdom, 2013.
13. Elanco, Inc. Prevention
and Control of Enteropathy/Ileitis in Swine. InnoCentive Challenge ID:9933892.
Waltham, MA: InnoCentive, Inc. Posted December 1, 2016. For an additional
example of an important pathogen-precipitated cattle disease, see reference 14.
14. Elanco, Inc. Prevention
and control of Streptococcus suis infections in swine. InnoCentive Challenge ID:
9933893. Waltham, MA: InnoCentive, Inc. Posted September 8, 2016.
15. Warrell et al. Oxford
Textbook of Medicine, 4th ed.; Oxford, UK: Oxford University Press;
2003.
16. Elanco, Inc. Prevention,
treatment or control of necrotic enteritis in poultry. InnoCentive Challenge ID:
9933891. Waltham, MA: InnoCentive, Inc. Posted October 14, 2016.
17. Elanco, Inc. Coccidiosis
prevention and control in poultry. InnoCentive Challenge ID: 9933890. Waltham,
MA: InnoCentive, Inc. Posted December 15, 2016.
18. Thormar, H.; Hilmarsson,
H. Chem. Phys. Lipids 2007, 150, 1. The role of microbicidal lipids in host-defense
against pathogens and their potential use as therapeutic agents.
19. Jackman, J.A. et al.
Molecules 2016, 21, 305. Nanotechnology formulations for antibacterial free
fatty acids and monoglycerides.
20. Dayrit, F.M. J. Am. Oil
Chem. Soc. 2015, 92, 1. The properties of lauric acid and their signifi- cance in coconut oil.
Clark. J.R. Botan. Gaz. 1899, 28, 289.
21. Thormar, H. Antibacterial Effects
of Lipids: Historical Review (1881 to 1960), in Lipids and Essential Oils as
Antimicrobial Agents; Hoboken, NJ: John Wiley & Sons, Ltd; 2011.
22. Cunningham, A.S. J. Pediatr. 1977,
90, 726. Morbidity in breast-fed and artificially fed infants.
23. Downham, M.A.P.S. et al. Br. Med.
J. 1976, 2, 274. Breast-feeding protects against respiratory syncytial virus
infections.
24. Winberg, J.; Wessmer, G. Lancet
1971, 1, 1091. Does breast milk protect against septicaemia in the newborn?
25. Adebonojo, F.O. Clin. Pediatr.
1972, 11, 25. Artificial vs. breast feeding: relation to infant health in a
middle class American community.
26. Welsh, J.K.; Skurrie, I.J.; May,
J.T. Infect. Immun. 1978, 19, 395. Use of Semliki Forest Virus to identify lipid-mediated
antiviral activity and antialphavirus Immunoglobulin A in human milk.
27. Welsh, J.K.; May, J.T. J. Pediatr.
1979, 94, 1. Anti-infective properties of breast milk.
28. The lipolytic cleavage mechanism
leading to lipid (triglyceride) antimicrobial activity, in vivo, was first observed
by Canas-Rodriguez and Smith. (a) Canas-Rodriguez, A.; Smith, W. Biochem. J.
1966, 100, 79-82. The identification of the antimicrobial factors of the
stomach contents of suckling rabbits; (b) Smith, H. J. Pathol. Bacteriol. 1966,
91, 1-9. The antimicrobial activity of the stomach contents of suckling
rabbits. Discussed in: Isaacs, C.E. et al. J. Infect. Dis. 1986, 154, 966.
Membrane disruptive effect of human milk: inactivation of enveloped viruses.
29. Isaacs, C.E. et al. Arch. Dis.
Childhood 1990, 65, 861. Antiviral and antibacterial lipids in human-milk and
infant formula feeds.
30. Thormar, H.; Isaacs, C.E.; Brown,
H.R.; Barhatzsky, M.R. Antimicrob. Agents and Chemo. 1987, 31, 27. Inactivation
of enveloped viruses and killing of cells by fatty acids and monoglycerides.
31. Kabara, J.J. et al. Antimicrob.
Agents Chemother. 1972, 2, 23. Fatty acids and derivatives as antimicrobial
agents.
32. Kabara, J.J. et al. Lipids 1977,
12, 753. Antimicrobial lipids: Natural and synthetic fatty acids and
monoglycerides.
33. Kabara, J.J. J. Soc. Cosmet. Chem.
1978, 29, 733. Structure-function relationships of surfactants as antimicrobial
agents.
34. Kabara, J.J. Nutr. Rev. 1980, 38,
65. Lipids as host-resistance factors of human milk.
35. Kabara, J.J. J. Am. Oil Chem. Soc.
1984, 61, 397. Antimicrobial agents derived from fatty acids.
36. Isaacs, C.E. Thormar, H. 1991. The
role of milk-derived antimicrobial lipids as antiviral and antibacterial agents.
In: Advances in experimental medicine and biology: immunology of milk and the
neonate. Mestecky, J.; Ogra, P.L., eds. New York, NY: Plenum Press, pp.
159-165.
37. Isaacs, C.E. et al. J. Nutr.
Biochem. 1992, 3, 304. Addition of lipases to infant formulas produces antiviral
and antibacterial activity.
38. Isaacs, C.E. et al. Nutr. Biochem.
1995, 6, 362. Antimicrobial activity of lipids added to human milk, infant
formula, and bovine milk.
39. Decuypere, J.A.; Dierick, N.A.
Nutr. Res. Rev. 2003, 16, 193-209. The combined use of triacylglycerols containing
medium-chain fatty acids and exogenous lipolytic enzymes as an alternative to
in-feed antibiotics in piglets: concept, possibilities and limitations. An
overview.
40. Bergsson, G. et al. APMIS 2001,
109, 670. Killing of Gram-positive cocci by fatty acids and monoglycerides.
41. Kelsey, J.A.; Bayles, K.W.; Shafii,
B.; McGuire, M.A. Lipids 2006, 41, 951. Fatty acids and monoacylglycerols inhibit
growth of Staphylococcus aureus.
42. Petra, Š. et al. Eur. J. Lipid Sci.
Technol. 2014, 116, 448. Formulation, antibacterial activity, and cytotoxicity
of 1-monoacylglycerol microemulsions.
43. Zhang, H. et al. Int. J. Food
Microbiol. 2009, 135, 211. Antimicrobial activity of a food-grade fully
dilutable microemulsion against Escherichia coli and Staphylococcus aureus.
44. Zhang, H. et al. Int. J. Pharm.
2010, 395, 154. Characterization and antimicrobial activity of a pharmaceutical
microemulsion.
45. Fu, X. et al. Int. J. Pharm. 2006,
321, 171. Physicochemical characterization and evaluation of a microemulsion
system for antimicrobial activity of glycerol monolaurate.
46. Fu, X. et al. J. Food Process Eng.
2009, 32, 104. Enhancement of antimicrobial activities by the food-grade
monolaurin microemulsion system.
47. Thormar, H. et al. App. Environ.
Microbiol. 2006, 72, 522. Stable concentrated emulsions of 1-monoglyceride of
capric acid (monocaprin) with microbicidal activities against the foodborne bacteria
Campylobacter jejuni, Salmonella spp., and Escherichia coli.
48. Bergsson, G. et al. Antimicrob.
Agents Chemother. 2002, 20, 258. Bactericidal effects of fatty acids and
monoglycerides on Helicobacterpylori.
49. Hilmarrson, H.; Thormar, H.;
Thrainsson, J.H.; Gunnarsson, E. Poultry Sci. 2006, 85, 588. Effect of glycerol
monocaprate (monocaprin) on broiler chickens: An attempt at reducing intestinal
Campylobacter infection.
50. Aurousseau, B.; Thivend, P.;
Vermorel, M. Annales de Zootechnique 1984, 33, 219-234. Influence of
replacement of part of the tallow in a food by tricaproqne or tricapryline in
association with coconut oil on the growth of young preruminant calves.
51. Diereck, N. et al. Livestock Prod.
Sci. 2002, 75, 129-142. The combined use of triacylglycerols (TAGs) containing
midchain fatty acids (MCFAs) and exogenous lipolytic enzymes as an alternative
for nutritional antibiotics in piglet nutrition. I: In vitro screening of the release
of MCFAs from selected fat sources by selected exogenous lipolytic enzymes in
simulated pig gastric conditions and their effects on the gut flora of piglets.
52. Diereck, N. et al. Livestock Prod.
Sci. 2002, 76, 1-16. The combined use of triacylglycerols (TAGs) containing
midchain fatty acids (MCFAs) and exogenous lipolytic enzymes as an alternative for
nutritional antibiotics in piglet nutrition. II: In vivo release of MCFAs in
gastric cannulated and slaughtered piglets by endogenous and exogenous lipases;
effects on the luminal gut flora and growth performance.
53. Bergsson, G. et al. Antimicrob.
Agents Chemother. 1998, 42, 2290. In vitro inactivation of Chlamydia
trachomatis by fatty acids and monoglycerides.
54. Lampe, M.F. et al. Antimicrob.
Agents Chemother. 1998, 42, 1239. Killing of Chlamydia trachomatis by novel
antimicrobial lipids adapted from compounds of human breast milk.
To view this issue
and all back issues online, please visit www.drug-dev.com.
Dr.
Ryan Littich is Innovation & Special Programs Manager at ABITEC
Corporation. He is responsible for the development of solution-driven lipid
excipient technology and applications. Professionally, he draws on experience
within a VC-backed biotechnology start-up, having led new product development
in an organization commercializing Nobel Prize-winning catalyst technology to
transform natural triglycerides into fine and specialty chemicals. He is a
classically trained synthetic organic chemist with a foundation in the de novo
synthesis of medicinally relevant, complex natural products. He earned his BA
in Chemistry from Ferris State University, and his PhD in Synthetic Organic Chemistry
from the University of Texas at Austin.