Night Magic Danes

Both, bacteria and viruses can cross the placental barrier and infect the embryo within. The magnitude and severity of symptoms is mostly effected by the time-frame of infection in relation to term week of pregnancy. Viruses and bacteria that infects the bitch in the first 5 weeks of pregnancy are often reabsorbed and are most of the time reported as missed breedings. Infections from 5-7 weeks can cause miscarriages, but in the 5-6 week timeframe most bitches will consume all evidence of miscarriage. Pregnancy is considered full term at 56 days once the suckling reflex is matured, natural birth happens normally at 63 days in the healthy bitch. Bitches that deliver Pre-term, but after the 56 day mark, should be evaluated for possible viral or bacterial infection. The exception to this is with very large litters that may also induce an early labor response.

Even though some viruses are able to cross this threshold, called vertical transmission, this is not a common practice as the placenta does a very good job protecting the embryo from advancing threats by a virus or bacteria by allowing no direct contact with the mothers fluids. What!? This is because the way a placenta works is more like a parasite than another part of the mothers body. The only place of direct mother to placenta contact is the site of implantation by the umbilical. Here, the placenta takes individual nutrients, broken down to their basic level, from the mother and then is able to move them through the trophoblastic receptors in the placenta. Imagine the placenta is kinda like a toddler who has built a lego fort, but cannot get it over his baby gate to show his mom….the placenta takes the nutrients, like lego’s, disassembles them and then passes them through the baby gate (the trophoblastic receptors) to the other side as small pieces that fit through the small holes. Then climbs over the baby gate to then reassemble them either in the same or in a different order, to take them to his mom, the embryo. This Type of sorted and monitored entry to the embryo’s environment ensures less risk of a viral or bacterial admission.

Most often, when pregnancy results in abortion or dead full term embryos, it is a result of placental infection at the implantation site within the uterus. When the contact site between the mother and the embryo becomes infected, the placenta illicit a placental defense, much like our bodies inflammation reaction is a primary results of our bodies fighting off an infection by trying to restrict the area of infection, as well as, concentrating the infection to more easily eradicate them from the bodies environment. The placenta will also become enflamed once a virus or bacteria has crosses the boundaries of the contact site, and triggers this response, this inflammation causes restriction in nutrient exchange. Unfortunately, Oxygen is one of the primary nutrients needed and used and the restriction of Oxygen to the embryo is what most often leads to the post-term death. This is also most often the causes of post term neurological problems. Other, later problematic issues, such as kidney failure, heart malformation, or skeletal mutation, may arise at a later date (post-labor) in puppies that have experienced prolonged placental inflammation. This happens because oxygen levels during development directly effect embryo development, so the type of problems associated with placental inflammation will depend on the stage of development that the embryo was in during the lower levels of oxygen.

The most common way viruses and bacteria infect a next generation is during birth during direct contact with the mothers mucus membranes and the freshly broken umbilical cord. Bacterial infection has a 3-5 day incubation period, so puppies exposed during birth will most often exhibit clinical signs of infection during the time frame. While viruses have a 7-10 day incubation period so puppies infected with a virus will exhibit clinical signs durn this time phase. These are the first two of four “humps” that are time-frame specific infections, and have the highest instances of documented post-term puppy deaths. By looking at age of death we can more accurately decipher the underling causes in an effort to prevent the problems in the first place.

Veterinary Medicine and Science » “Canine Medicine – Recent Topics and Advanced Research”, book edited by Hussein Abdelhay Elsayed Kaoud, ISBN 978-953-51-2832-8, Print ISBN 978-953-51-2831-1, Published: December 21, 2016 under CC BY 3.0 license. © The Author(s).
Chapter 3

Infectious Causes of Abortion, Stillbirth and Neonatal Death in Bitches
By João Marcelo Azevedo de Paula Antunes, Débora Alves de Carvalho Freire, Ilanna Vanessa Pristo de Medeiros Oliveira, Gabriela Hémylin Ferreira Moura, Larissa de Castro Demoner and Heider Irinaldo Pereira Ferreira
DOI: 10.5772/65330 https://www.intechopen.com/books/canine-medicine-recent-topics-and-advanced-research/infectious- causes-of-abortion-stillbirth-and-neonatal-death-in-bitches

JPC SYSTEMIC PATHOLOGY
RESPIRATORY SYSTEM
October 2017
P-V21 https://www.askjpc.org/vspo/show_page.php?id=622

Pathogens and the Placental Fortress https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3265690/

PLACENTA
Jump to:navigation, search
PLACENTA (Latin. placenta, from grech, plakus flat cake; synonym afterbirth) — the provisional body which is formed during pregnancy and providing communication of a fruit with an organism of mother. http://bigmed.info/index.php/PLACENTA

Monitoring of the newborn dog and prediction of neonatal mortality
Author links open overlay panel HannaMilaabAurélienGrelletaMarineDelebarreaClaireMarianicAlexandreFeugiercSylvieChastant- Maillarda

https://www.sciencedirect.com/science/article/pii/S0167587716306468

There are many types of bacterial infections the can occur in the neonate pup, but the most common types that have occurred in autopsied neonate canines less than 4 weeks of age are several of the Staphylococci species especially Staphylococcus aureus, Escherichia coli. As well as beta-hemolytic Streptococci, especially species Streptococcus Canis being the most prevalent of the Streptococci, but also Streptococcus agalactiae or equi, subspecies zoopeidemicus . These species can often be identified as ‘normal’ flora of an adult canines urogenital tract and is often the site of infection during birth, especial attention should be given to puppies born already out of the embryonic sac, as these puppies will have the most direct contact with the mothers reproductive tract. In the adult canine small quants of these bacteria is kept under control with the natural balance of good and bad gut bacteria and often poses no outward symptoms. The neonate pup is a different story because of its underdeveloped immune system, immature good gut bacteria, and lower body temperature, which allows opportunistic infections from these common bacteria.

What is an opportunistic infection you ask, it is when a body undergoes a stressful condition, lowering natural immunities, and allowing, usually several overgrowths of bacteria that is normally kept in check by the body. This combined effort of several lesser infections causes a domino effect that continues to lower the bodies immunes and defenses as more and more bacteria overgrow. Causes of the initial stressors can be birth, a dirty environment which would have an excessive amount of feces , allowing for greater infection rates. A puppy becoming chilled, or not receiving enough antibodies from the mother, or even just a large litter can stress out puppies by having the constant stress of having to compete for a limited food, and the constant movement that a larger litter entails, so individual rest per puppy is down, as well as the mess per pup often being up and this will often result in the smaller pups becoming weaker due to minor bacterial optimistic infections.

Now lets look a little closer at a few of these bacterial infections. Staphylococcus aureus, a gram positive round bacterium, that is a type of normal body flora frequently found in the nose, respiratory tract, and skin and in overgrowth it is a major cause of most skin infections. These can include pimples, impetigo, boils, cellulitis, folliculitis, carbuncles, scalded skin syndrome, and abscesses, to life-threatening diseases such as pneumonia, meningitis, osteomyelitis, endocarditis, toxic shock syndrome, blood stream infections, bone or joint infections, bacteremia, and sepsis. Transmission of Staphylococcus is mainly through touching of contaminated surfaces, like during the birth process or through afterbirth contaminating bedding.

Escherichia coli, however is a gram negative bacteria, read harder to kill with fewer broad range antibodies. It is rod shaped and many harmless strains are commonly found in the lower intestines of warm blooded organisms, and are actually beneficial to the host by providing vital K2 as their wast, but some strains can cause serious food poisoning due to food contamination and this is often the case for dog food recalls that have lead to the death of puppies and adults generally through intense diarrhea that kills through dehydration . E. coli is shed in the facial material and reproduced rapidly for three days before numbers start to decline outside of the host, during this time contamination of the environment happens which can lead to multiple outbreaks in the area. As with most bacteria incubation time from infection time is 3-4 days but can be as little as one day and as long as 10 days.

References

Neonatal Mortality in Puppies Due to Bacteremia by Streptococcus dysgalactiae subsp. dysgalactiae

Ana I. Vela1, Enevold Falsen2, Isabel Simarro1, Eduardo Rollan4, Matthew D. Collins3, Lucas Domínguez1 and Jose F. Fernandez-Garayzabal1,*

http://jcm.asm.org/content/44/2/666.full

Staphylococcus aureus
From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Staphylococcus_aureus

Causes and Symptoms of Staphylococcus aureus
Minnesota Department of Health Fact Sheet
Revised February, 2010
Download a print version of this document: Staphylococcus aureus Fact Sheet (PDF: 35KB/1 page)

http://www.health.state.mn.us/divs/idepc/diseases/staph/basics.html

Escherichia coli
From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Escherichia_coli

Different types of Bactria have different types of cell walls surrounding them, protecting them in different ways from the environment. Due to these walls having different traits they subsequently have different successful methods of breaking through these barriers in order to defeat the invading Bactria. Assessing the differences in the cell walls is key in understanding how to break through these very different membrane surfaces, by determining the type of antibiotic that will be most effective against either you’re gram positive or gram negative Bactria.

The Gram positive Bactria, has a much thicker, more absorbent membrane, which *The American College of healthcare and sciences, in the article Medical Terminology: Gram Positive Vs Gram Negative Bacteria, describes as being like a heavy wooden privacy fence, or like the walls of a room, with 2×4’s, insulation, drywall and siding. It is thick and heavy and has greater volume and greater ability to absorb other particles when compared to gram negative bacteria which is likened to chain mail, or kevlar bullet proof vests, which are thin but practically impenetrable to high impact assaults because they are designed to spread out the impact over a greater area, and they also have little absorption rates. Now while you may be thinking that gram negative bacteria is a super villain, do not fret, it does have its kryptonite. For one, gram negative Bactria has no ability to defend against extreme temperatures, because unlike the nice thick walls of a gram positive bacteria, the thin, if strong, walls of a gram negative Bactria have no insulating power. This means that they can be more readily killed by long term high or cold temps. They also have little defense against a targeted small entry point, like using a knife with a Kevlar suit, it will push right through. If, however, you were to use these same practices on the gram positive bacteria, they would not prevail, even though the gram positive bacteria, generally speaking has the easier to penetrate cell wall, because just like walls of a house, compared to kevlar suite, your weapon of choice should directly pertain to the ‘how’ of getting it through the protective coating and into the bacteria’s center and when you are trying to break through a wall, a knife may not be your weapon of choice, as it will not be able to get though the thick boundaries of a wall, the same as it will penetrate a thin kevlar suite. This is the same if you are trying to use temperature change to kill it, the greater membrane volume of a gram positive bacteria is also better suited to insulated it against more extreme temperatures, than when compared to the super thin walls of gram negative membranes . This also shows that a gram negative bacteria is more ready found in more sheltered temperature regulated habitats, and more easily killed in open areas with a wide temperature threshold… While a gram positive bacteria can survive in the open environment for much longer as it can more readily withstand ultra violet lights, along with heat and cold.

Also, With Gram positive bacteria, many broad spectrum ‘power house’ antibiotics have been developed which can easily blast through their cell walls like a gun bullet through drywall, but even though we have ways to kill most bacteria, they continue to progress in their abilities to evade our antibiotics. Mainly when you do not take antibiotics until all of the bacteria is gone, what happens is any living bacteria still around when you stop taking the meds, will naturally have a greater resistance to that drug, by the natural process of cell mutations, but then when only this bacteria is left alive to multiply, then, only its traits are replicated thereby passing along its natural resistance to the antibiotic to ALL of the new generation, if you do this process for enough generations it will result in a bacteria that is fully resistant to your medication…. Just like we as humans have evolved to create fire-resistant insulation, or water and mould resistant wood, the bacteria have also found a way to overcome their reoccurring obstacles, us…

References

American College of Healthcare Sciences: Medical Terminology: Gram positive vs. Gram negative Bacteria, written by Jared Schaalje, apr 12, 2013 2:47 pm

http://info.achs.edu/blog/bid/282924/Medical-Terminology-Gram-Positive-vs-Gram- Negative-Bacteria

Bacteria is present in all healthy dogs and the environment, so puppies will be exposed to bacteria and have cultures started within a few hours of birth, and like with many things there is good with the bad. In general a healthy mom, with a good milk supply will provide a passive immunity to the puppies through her colostrum within the first 48 hours of birth. The absorption rates are best during this period due to the larger molecular size of colostrum being easier to absorb when the immature intentions have larger opening size, which is the first few days after birth. The intestines of delayed birth puppies may have already matured past the ideal absorbing rates for colostrum, which may in turn make these puppies more susceptible to common bacteria in the environment. But even once the intestine have close past the ideal absorption point, having the mothers milk will still coat the oropharynx and intentional tract with antibodies providing at least some additional protection.

The most common forms of treatment will include antibiotics, but when dealing with the immature liver function, lower blood proteins *albumin, as well as lower body fat, with a poorly developed blood brain barrier the type of antibiotic used becomes more precise. The most common will be you antibiotics with the least side effects, and these would be the penicillins and the cephalosporin as they provide good coverage of many types of bacteria. The Aminoglycosides are very effective but immature renal function may effect dose so care should be taken with these Potentiated sulfonamides. The tetracyclines while also treating a broad range, they can cause pitting of the enamel of teeth and cannot be given with any type of calcium or magnesium, as these can interfere with absorption rates, but this means puppies cannot drink milk! The fluorquinones are excellent in older dogs but have a great risk of causing cartilage defects in young dogs, and puppies.

Along with antibiotic care a neonate will need to be kept in a clean, warm, stress free environment, which the mom provides a large part of, the constantan licking and cleaning that a mom routinely preforms encourages a puppies survival reflex, and the stimulation encourages the puppy to struggle and search for a nipple. When a puppy is removed from the mother care, touch should be given to the puppy as often as possible to encourage its survival. Along with this there are several immune supportive vitamins that can be given to support immune health like vitamins C, echinacea, garlic, the B’s, as well as superfoods which have higher natural levels of antioxidants and photochemicals. Only when immune support along with proper environmental conditions are not adequate for the increased well being of the pup should antibiotic care be administered, as antibiotics will kill both good and bad bacteria and some of the good guys are needed for proper health and getting rid of them can cause alternate effects.

References

Bacterial Infections in Young Puppies
Author: Debra M. Eldredge, DVM
Editor: Johnny D. Hoskins, DVM, PhD, Dipl. ACVIM http://www.lowchensaustralia.com/health/bacterialpups.htm

Neonatal Immunology

Download Neonatal Immunology.pdf (559.52 KB)
John Tregoning, Imperial College London, UK https://www.immunology.org/public-information/bitesized-immunology/immune- development/neonatal-immunology

What Are Superfoods?
By Christopher Wanjek | May 11, 2015 09:15pm ET https://www.livescience.com/34693-superfoods.html

Therapeutic touch: influence on vital signs of newborns. [Article in English, Portuguese]
Ramada NC, Almeida Fde A, Cunha ML. https://www.ncbi.nlm.nih.gov/pubmed/24488378

Therapeutic touch: influence on vital signs of newborns Einstein (Sao Paulo). 2013 Oct-Dec; 11(4): 421–425.
doi: 10.1590/S1679-45082013000400003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4880376/

5 Foods for Colds and Flus – Naturally Boost Your Immune System! https://healthfree.com/foods-for-flu-boost-immune.html

A virus is a bundle of RNA or DNA that very closely resembles another organisms RNA or DNA strands, Wrapped up in a sheath of protein to keep it together, and sometimes the sheath may be coated in lipids to protect it while outside the hosts body. This make-up tells us one thing, the a virus has no ribosomes which mean that it cannot produce proteins of its own, and it needs a host cell to produce the proteins needed to replicate itself. This is the very definition of a parasite, and that is the truth a virus is that it is a parasite that uses a hosts cells to replicate its-self.

Good news for viruses, bad news for anything non-virus as viruses can infect not only animal based organisms but anything that has cells that can reproduce, so bacteria, fungi, plants, and animals, are all susceptible to a viruses invasion.
Ok, so now we understand why a virus needs another organism… but now we need to know how it does it… Why do we get sick? Remember how I said a virus is a bundle of RNA or DNA… well it is kinda like code, or a recipe on how-to-make-another-virus. The virus punctures the cell wall of the first cell it encounters, once punctured it regurgitated all of its genetic material ‘code’ into the inside of the cell, which is close enough to the cells code that the cell starts to read this code rather than the cells existing code. Think of it like this, your in the kitchen making peach pie for your boss and then your kid swaps your peach pie recipe for banana bread recipe, and you not knowing this followed the directions and bam an hour later you have made what you think is peach pie… but it is really banana bread….. now replace peach pie with more healthy human cells and replace the banana bread with virus cells… and now you have a infected system full of virus cells that your body is now making instead of healthy cells! Talk about stealth mode!

New discoveries are advancing in the field of visual studies in understanding how these viruses are read by our ribosomes. This has everything to do with the 3D twisted shape of virus RNA or DNA forming pseudoknots in the strand. As this psuedoknot moves along the ribosome to be read the ribosomes gets stuck at the knot, and slips backward along the strand, effectually reading the ‘code’ backwards, this backward read code, is the actual false directions that instruct the cell to produce more viral cells rather than more health original cells. Also, the tighter the puesdoknot is the more times the ribosomes with ‘slip’ and read the code which etc time generates another viral cell, so the viruses with the digest puesdoknots are the viruses that are the quickest reproducing and this makes them the more virulent stands. This breakthrough in the structure of the virus has been a key finding, as understanding the Why and the How of the thing that is causing a problem, will often lead you to see ways around your problem. For instance if we could find a way to iron out, or even loosen the puesdoknots there would be no or at least less slipping and therefor no, or at least less backward read code, effecting weakening or even completely disarming the virus.

References

How Viruses Make Body Cells Work For Them
University of Copenhagen. “How Viruses Make Body Cells Work For Them.” ScienceDaily. ScienceDaily, 2 April 2007. <www.sciencedaily.com/releases/2007/03/070330100654.htm>. http://microbemagic.ucc.ie/about_microbes/ugly_viruses.html

Viruses: What are they and what do they do? Last updated Tue 30 May 2017
By Peter Crosta Reviewed by University of Illinois-Chicago, School of Medicine https://www.medicalnewstoday.com/articles/158179.php

How does the body fight off a virus? http://www.bbc.co.uk/science/0/22028517

There are numerous verities and strains of viruses in the canine, just as there are for people. This is because a virus mutates easily, what does this mean? It means that each generation of cell division can be slightly different than the generation before, and because of how fast the division happens, as quickly as a new generation every 20 minuets! The faster a virus duplicates the more contagious it is considered and it is given a higher epidemic possibility rating. With this fast division it does not take long for the generations to fully distinguish themselves into a virus that the body no longer recognizes and antibodies no longer work for. When this happens it is considered a new strain and infection can happen again.

For the most part viruses are not inter-species compatible and are instead species specific. This means that a virus that effects a canine will not usually be able to infect a equine or a human. There are a few viruses that have, however, crossed the species boundary, and it is these that a lot of attention and research are put into because when you have a virus capable of crossing one species boundary that means that it has a higher probability of jumping to humans and if a highly contagious, and volatile virus ever jumped to humans it could be devastating before a vaccine was developed so Scientist focus a lot of their attention on these viruses.
The Canine Coronavirus is a relative new virus to canines and one strain is said to have come from Bovine, while the other pigs, its rate of division is very high so this virus has mutated often and occasionally jumped species and now has a strain that effects most animals. Each strain is, however, different enough that a bovine coronavirus will not effect a canine and visa versa, without another mutation anyways. It is considered a lesser virus and early causes death in healthy individuals and adults often express no symptoms. When death happens often another virus or bacteria is found which has allowed the coronavirus a weaker immune system.

The Canine minute virus, also know as Parvo type 1 or CMV is not as nice and it is capable of transplacental transmission to the fetus and is responsible for fetal resorption when it has been transmitted late in gestation, resulting in weak or dead pups. It said to be found in serologic prevalence in the US at 50% of all adult dogs, but in the adult dog symptoms may be as mild as a brief cough, or diahreah that could be confused with a bordetello infection. In puppies it may cause enteritis, pneumonitis, myocarditis, lymphadenitis, and may show diarrhea, vomiting, and dyspnea and have a continual cry. But unlike Parvo, which is its descendant, puppies have a much greater chance of survival.

Parvo, however, is a more verdant and destructive strain of the Minute virus. And has a 80% kill rate in unprotected pups and a 50% kill rate in antibody protected pups, but puppies that have immunities and are given ample round the clock fluids have a 90% survival rate. As death from the intestinal form of Parvo comes from dehydration from the constant vomiting and diaherah and treatment with intervienious fluids and stomach relaxers. The gestational form of Parvo, meaning that the puppies contract the virus in the last few days of gestation with tranplancental transmission or during birth, it effects the heart, and has a 90% kill rate, with surviving pups having possible heart, brain and kidney damage. Parvo is especially dangerous because it can survive long periods of time in the environment without damage. Up to and over 1 year and potentially over 6 years in the soil, or other protected place. Parvo is the most recognized of canine viruses because of constant outbreaks due to its ability to exist so long in the environment.

All of these viruses and all of the most common viruses can normally be prevented with puppy shots and up-dates that provide an immunity to the puppies past when the mothers immunities have worn off. Antibodies wear off in puppies between 6-16 weeks of age, and so long as puppies have received plenty of colostrum from their mom at birth, and so long as the mom has either received a shot or been exposed to the virus in the environment she will have antibodies that will protect the puppies at least till 6-16 weeks, during the 6-16 week period the puppies should receive a series of shots to ensure the shot is given after the moms antibodies have wore off, but before environmental exposure of the virus.

References

Canine Parvovirus Infections and Other Viral Enteritides

Jane E. Sykes, in Canine and Feline Infectious Diseases, 2014https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

Canine Coronavirus Infection in Dogs

https://wagwalking.com/condition/canine-coronavirus-infection

Respiratory Viruses

H.F. Boncristiani, … E. Arruda, in Encyclopedia of Microbiology (Third Edition), 2009 https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

DNA-Containing Viruses

JAMES H. STRAUSS, ELLEN G. STRAUSS, in Viruses and Human Disease (Second Edition), 2008 https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

Veterinary Vaccines and Diagnostics

M.J.G. Appel, in Advances in Veterinary Medicine, 1999
IV.
Canine Parvovirus https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

Viral Infections

James F. Evermann, Melissa A. Kennedy, in Small Animal Pediatrics, 2011 https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

Infectious causes of abortion
Donald H. Schlafer, Robert A. Foster, in Jubb, Kennedy & Palmer’s Pathology of Domestic Animals: Volume 3 (Sixth Edition), 2016 https://www.sciencedirect.com/topics/veterinary-science-and-veterinary-medicine/ canine-minute-virus

The body does not have just one defense against invading viruses, but many. The first defense is the skin, which also includes mucus membranes at the entry ways to our body, the mucus will push out foreign substances in the following ways; you will cough or sneeze to dispel any from air passageways, you will vomit, or have diarrhea in an attempt to rid your body of the invading army. Even your temperature is a defense again viruses as they have a very narrow temperature threshold for optimal growth, so your body overheats us in an attempt to kill the virus. Even still, some viruses are more resistive and can still overcome our first defenses and start overcoming our initial responses. The next step is fought on at the cellular level with differentiated cells called B cells and T cells. Both cells originate from the bone marrow but for the B-cell that is where its development is completed and mature B-cells emerge from the bone marrow, and go on to engulf foreign viral cell bodies by surrounding them and effectively eating them, during this process they mimic the ‘code’ of the virus cell, kinda like making a mold of a lock and key found on the virus and then once fully ‘eaten’ they expel plasma and the secreted antibodies which are the *Key copies for the lock found on the virus. These ‘key’ copies are the ‘death’ for that virus, because it will let our killer T cells inside. These T cells emerge from the bone marrow also just not yet fully developed, at this stage they are considered double negative because they do not have a complete TCR, CD4 or CD8 and they make there way to the cortex of the Thymus where they start to form a TCR and now because they can synthesize both CD4 and CD8 they are considered double positive *DP. This process is particular interesting to me because 97% of all cells will produce a TCR that does not bind to any peptide and will die off through neglect of not being used. The remaining 3% of cells that do produce a TCR that does bind to a peptide presented in class 2, will stop expressing CD8 and become CD4 T cells, these cells go on to be Th1 cells in cell medicated immune responses and Th1 helper cells for cytotoxic T lymphocytes as well as the Th2 helper cells needed to help the B-cells . This process is called positive selection. The next process called negative selection which happens in the medulla of at the Thymus and the process selects out any cells who binds very strongly to the self-peptides and self-MHC and are again effectively killed by apoptosis *neglect . The negative selection process is a very important part because the cells that bind to tightly are the ones in danger of mounting an autoimmune attack, which could be just as dangerous if not more so than the invading virus.

Once The Killer T cells are equipped with the antibodies *key code they are able to bine to the unique peptides in the virus and secrete molecules that destroy the cell to which it has bound. All of the differentiated cells will fight different things, the CD8 cells can hunt out and find virus fragments on the surface of cells, and destroy the cell before releasing a new crop of viruses. The CD4 cells bind to a class II molecule and will release and attractant for more cells to come and help. This larger group of cells will cause inflammation as they attempt to wall off the viruses and destroy the material, and example of this is an abscess or rash to poison.

At this point I would like to bring back up the negative selection process because all cells express fragments or molecules derived from self peptides. Which presents the perpetual risk of the T-cells recognizing these fragments as an invading army and mounting that auto immune response I talked about earlier. So an important note is that moderation within the system of our immunity has a very important donation, as it does in so many areas of life.

References

How does your immune system help you fight colds and flu?
By ABC Health and Wellbeing’s Dr Jocelyn Lowinger
Updated 6 August 2015 at 1:58 am
First posted 6 August 2015 at 1:34 am http://www.abc.net.au/news/health/2015-08-06/how-does-your-immune-system-help- you-fight-colds-and-flu/6650768

How Your Immune System Fights Infection https://www.webmd.com/cold-and-flu/immune-system-fight-infection#2

B Cells and T Cells http://www.biology-pages.info/B/B_and_Tcells.html

Pneumonia is an infection of the lungs, leading to the inflammation of the airways and excessive amounts of mucus build up. This is all an effort of the immune system to rid the body of a foreign contaminate. Perhaps you can see how a bunch of mucus buildup conensidung with lung inflammation which causes restricted airways, might escalate quickly into a problematic situation, and this is especially dangerous to the underdeveloped, tiny lungs and immature immune system of the neonate canine. This infection can effect one or more lobes of the lungs (called Lobar Pneumonia) or it may effect the lungs in patches (known as Bronchial Pneumonia). Pneumonia can come from a variety of sources and can be; viral, bacterial, mycoplasma, as well as a few cases coming from unknown causes. For our report we will be focusing on Bacterial and Viral Pneumonia. In the neonate canine, pneumonia can cause death in just hours, from onset of symptoms, which is why it constitutes such a large percentage of neonate deaths. Treatment and prevention of pneumonia is dependent on the underling causes.

Bacterial Pneumonia, as the name indicates is causes by bacteria that invades the lungs. Some of the most common bacterial infections come from Bordetella bronchiseptica, Streptococcus zooepidemicus, Pasteurella multocida, Pseudomonas aeruginosa, Klebsiella pneumoniae, E. coli and Mycoplasma species. Symptoms include increased temperature, coughing, lethargy, runny nose, dull eyes, little or no appetite, and a change in breathing rate, low blood oxygen levels leading to a bluish tint to gums. If the condition persists, the dog may suffer anorexia or severe dehydration in extreme cases. Odds increase with very young or very old dogs. Bacterial Pneumonia is easily treated with antibiotics if you can identify the bacteria, but even with no identification there are many broad spectrum antibiotics available that will target a large rage of either gram positive or gram negative bacteria.

Viral Pneumonia, again as the name indicates, comes from a viral source. Some of the leading causes of Viral Pneumonia are Canine distemper virus, adenovirus types 1 and 2, canine influenza virus, and parainfluenza virus. Once infected, Viral Pneumonia is not able to be treated, other than to support the bodies immune response. This will include temperature perimeters being met, sufficient sanitation, adequate fluid and nutrient intake, vitamin and electrolyte supplementation as well as immune support like vitamin C, B12, echinacea and other immune supportive and antioxidants rich supplements. Prevention is the main way to avoid viral Pneumonia cases, and there are many antiviral shots available that cover the main viral stands, many of the shots can be found that not only include nation wide problematic viruses like Parvo, but also geographically located viruses like certain strains of canine influenza. If these shots are administered within 6 months of birthing the antibody levels in the mothers milk will be at its highest levels to convey the antibodies through passive immunity to her puppies in the fist 24 hours of life. Shots given years in advance of a litter will still impart some amount of immunities in the puppies but are often found at much lower values than recently vaccinated bitches.
Presentation of viral Pneumonia is the same as presentation of bacterial pneumonia.

References

Managing puppies with pneumonia (Proceedings) http://veterinarycalendar.dvm360.com/managing-puppies-with-pneumonia-proceeding

Viral Pneumonia https://www.webmd.com/lung/viral-pneumonia-lung-infection

What Is Viral Pneumonia? https://www.webmd.com/lung/viral-pneumonia

Pneumonia in Dogs
By Ned F. Kuehn, DVM, MS, DACVIM, Section Chief, Internal Medicine, Michigan Veterinary Specialists
Neil W. Dyer, DVM, MS, DACVP, Director and Pathologist, Veterinary Diagnostic Laboratory, North Dakota State University
Joe Hauptman, DVM, MS, DACVS, Professor of Surgery, Veterinary Teaching Hospital, Michigan State University
Steven L. Marks, BVSc, MS, MRCVS, DACVIM, Clinical Professor of Emergency and Internal Medicine; Associate Dean and Director of Veterinary Medical Services, North Carolina State College of Veterinary Medicine
Stuart M. Taylor, PhD, BVMS, MRCVS, DECVP,
disorders-of-dogs/pneumonia-in-dogs http://www.merckvetmanual.com/dog-owners/lung-and-airway-disorders-of-dogs/pneumonia-in-dogs

Pneumonia https://www.hopkinsmedicine.org/healthlibrary/conditions/respiratory_disorders/pneumonia_85,P01321

Canine Influenza
Last Full Review: November 2015 Minor Updates: February 2016 http://www.cfsph.iastate.edu/Factsheets/pdfs/canine_influenza.pdf

Streptococcus Canis is a G beta-hemolytic species of Streptococcus. It is also part of the healthy microbiota of dogs and cats, that promote healthy mucosal and skin health. When opportunistic infections occur, read overgrowth, and keep in mind that our body is like a scale, to much one way or the other and the whole system falls over, so keeping bacteria in the middle rage of growth is important to receive potential benefits from them, to little or to many can cause system stress and allows for opportunistic infection. During infection, the bacteria have been known to cause neonatal septicemia, abortion, and cellulitis in dogs. In addition, S. canis is also responsible for streptococcal toxic shock syndrome and necrotizing fasciitis. The main causes for overgrowth of this bacteria is overcrowding of a population as overcrowding cause stress on a cellular level allowing overgrowth as well as remaining in confined spaces for long periods of time… like kennels with no outside access. Death results in the very young and old of the population as well as already weak individuals. The development of disease can occur rapidly, and symptoms include skin ulceration, chronic respiratory infection, and necrotizing sinusitis. The persistence and spread of these bacteria in a confined area can lead to both sepsis and death, quickly resulting in above average levels of mortality among susceptible canines. Treatment is relative simple as this bacteria has no immunities for antibodies due to it not being a huge killer unless circumstances are right. Best practices of management are a clean environment, to allow fresh air and outside access to a clean area and to not overcrowd animals.

Streptococuss Agalactiae is a group B strep also know as GBS, and is a round gram positive bacteria, with a tendency to form chains. Again this is another ‘normal flora’ colonizing the gastrointestinal and genitourinary tract of up to 60% of canines, and 30% of humans and can be transferred through mucus membrane contact during birth. It does not pose a problem in the health adult. But it can be devastating for a new born exposed during birth . And it is the major cause of several bacterial infections of the newborn neonatal infection septicemia, pneumonia, and meningitis, which can lead to death or long-term sequelae . In the neonate pup early symptom onset will be at 1-3 days after birth and presents as fluid build up behind the eyes causing a ‘pop eye’ effect. With out treatment, which consists of releasing pressure of the eye, permeant damage can come from the rupture of fluid filled eye resulting in blindness, and secondary infection of the eye. Presentation after day 7 will normally self correct as the eye will be open enough to drain fluids naturally. Prevention can be excessed with antibiotic treatment 1-3 days prior and 1-3 days post birth. This is also the bacteria most commonly at fault for Mastitis .

Streptococcus zooepidemicus is another gram positive bacterial infection that manifests itself similarly to human Toxic Shock Syndrome, causing a severe, bloody pneumonia in dogs. It has an acute onset and in a small proportion of cases the disease has been known to kill dogs within 24 hours of contracting the infection. With mortality rates being as high as 50%. Presentation is normally similar to kennel cough, and can include fever, accompanied with sneezing, nasal discharge, which is often bloody, lethargy, and death by hemorrhagic pneumonia. Dogs can be silent carriers, meaning they will have no symptoms but can still pass it on to others, this is a highly contagious disease. However, fatal cases of Streptococcus zooepidemicus, in canines is generally also associated with multiple opportunistic infections, such as Bordetella, or other bacteria that diminish the immune system and allow the opportunistic infection to take root. It has its most common transfer is from equine, where it is considered a normal bacteria, but also can come from pigs, cows, goats, cats, sheep, Guinea pigs, and even humans . This bacterium is most commonly seen in assesses and uteruses and can cause late term abortion in canines.

References

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Streptococcus_canis

Streptococcus agalactiae

From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Streptococcus_agalactiae

Group B Streptococcus (GBS) Infections https://emedicine.medscape.com/article/229091-overview

Nonpneumococcal StreptoCOccal Infections, Rheumatic Fever
Donald E. Low, in Goldman’s Cecil Medicine (Twenty Fourth Edition), 2012 https://www.sciencedirect.com/topics/medicine-and-dentistry/streptococcus- agalactiae

RVC highlights signs of potentially fatal bacterial disease affecting the canine community
13 May 2014 https://www.rvc.ac.uk/News/PressReleases/pr1405-streptococcus- zooepidemicus.cfm

Characterization of Pneumonia Due to Streptococcus equi subsp. zooepidemicus in Dogs
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2976090/

Streptococcus zooepidemicus https://microbewiki.kenyon.edu/index.php/Streptococcus_zooepidemicus

In conclusion, viruses and bacteria are everywhere, they are in the soil, the water, the air, and even living inside of our bodies very happily. Prevention can come from many avenues, whether it is sanitation, avoidance of high traffic area where high volume of them may be evident like dog parks, or standing pools of stagnant water, or where excessive amounts of feces have built up, or in complimenting immune health with correct diet and exercise, to provide the body with the building blocks necessary to stay healthy, and fight off the infection. In the end if we want to avoid as many problems as possible all of these measures should be followed.

Viruses are the most strait forward. They have the highest kill rate once infected, and consequently have the most research done to minimizes the risk of an outbreak through the use of vaccines. Vaccines are crucial to the prevention of viruses, moms that are fully vaccinated once having pups will pass on these antibodies to the babies and in turn they are protected. To be very safe a breeding female may be given a vaccination at the time of her breeding heat, this will ensure the very highest concentration of antibodies in her milk. Continued nursing through 5 weeks of age will also coat the intestine with these antibodies even if the babies can no longer absorb the large colostrum molecule, providing this coating can help to kill the infection before it is able to get past the intentional boundary. If a kennel gets a virus in that kills puppies most likely it will be the only time that female, or others infected at the time of the outbreak, will have future litter deaths associated with that specific virus, as after she has come in contact with it she will then have an immunity to pass to her pups for that virus for the rest of her life.

Bacteria is a bit more elusive, as the body cannot fight bacteria in the same way and each infection is taken as a new infection no mater how many times a dog will get it, as there are no remembered immunities for bacteria. But in general only one type of bacteria will not kill a puppy, but yet, bacterial infection still make up the largest portion of neonate deaths in canines. This is partly due to a lack of research on the subject, and this is in part due to the fact that bacterial infections are opportunistic, meaning they wait for the perfect moment to attack, when the immune system is already down. This may come from a viral infection, even if the puppy is protected by the mothers colostrum, there is still a immune decline until the pups immunities can eradicate the virus, and during this time is when a bacteria may attack. Dirty or stale environments can lead to an overgrowth of bacteria, and what would have been an acceptable amount for the body to defend against now may be to much, like how one fire ant can be squashed but if you are contained with a trillion of them, you may just get eaten. Also bacteria works off of each other, so as soon as the bodies immune system starts to be lessened from one type of bacteria that has been introduced to the environment, and the body starts to fight that, another bacteria, perhaps common to the body, takes this ‘opportunity’ and overgrows as well, then the body is fighting off two infections, this lowers the immunities more, and another bacteria overgrows, and now the body is fighting off three infections and this continues until the point the battle is lost and the pup dies. As is often the case with bacterial death, one bacteria is most often not the cause but a combination of a few different types of bacteria and or a virus. Bacterial infections are best prevented with a clean environment of an appropriate temperature, and adequate ventilation, sunlight, and immune support through proper dietary needs and a stress free environment. Once infected there are options, and antibiotics are often very effective against many bacteria. In addition to this is a natural immune system support. All together environment, antibiotics, and immune support will give a puppies its best chance of survival against a bacterial infection.

All in All providing the mother and pup with the highest levels of nutrition, in a stress free and clean environment from conception through weening will provide the best chances of recovering from either a bacteria or virus, as even with the help of vaccines or antibiotics, nothing can compare to the amazing abilities of a strong functioning immune response. This is not to say that the immune system alone can always tackle and win every battle, and vaccines and antibiotics are invaluable, but with out a healthy immune system as your foundation, all the rest can crumble and fall. So start with your base make it strong and then provide outside help as needed, and your base will be strong enough to hold it all together, and make your pups survival that much more certain.

The Liver is what filters our blood, and in the neonate the liver is not yet fully formed, and functional tests of normal puppies have shown that glomerular filtration rates at birth range only 20-50% as that of an adult, this leads to slow filtration of toxins increased sodium levels and inability to conserve fluids. This in combination with an immune attack whether it is from a virus or bacteria can lead to multiple problems within the liver. An overworked, immature liver may not form properly through the sickness, leading to blood filtering problems in the future. Most of the time the liver is not effected, but certain illnesses, especially long lived ones can cause secondary problems with formation. Among these are several EBV associated infections, like hepatitis and even mild elevations of alkaline phosphates at 60% rate of liver damage, as well as mild elevations of aminotrransferases, that last up-ward of two weeks of illness can result in a 90% rate of liver damage. Cytomegalovirus (CVM) a member of the Herpes family, if infected as a neonate can have 60-100% seroprevalence in adults. The true canine herpes also gives lasting damage to neonates at a rate of 62% with acute liver failure as a young adolescent. There are also several mosquito viruses that will effect liver development, these include Zoonotoc also know as breakbone fever’ as well as a viral hemorrhagic fever.
There are however more problems associated with bacteria effecting the liver long term. Even the indirect impact of these infections that are seen with the common sepsis, have dramatic effects. The formation of accesses is a common problem form many bacterial infections. Brucelloses which is the common kennel cough if infected as a neonate can cause lesions formation, granulomas, bile duct calcification, and hepatomegaly and these symptoms can take up to a year to manifest.

The heart is another sensitive organ for neonates that can have lasting effects on adults that have recovered from a notable illness. Parvo is a big one here, as puppies that are exposed to Parvo during gestational, will get the heart form of Parvo, even after recovery, it can stay dormant in the cardiac fibers of the heart, leading to heart failure as an adult . This is because the neonate heart prior to two weeks of age is unresponsive to atropine due to the immaturity of the vagus nerve, the baroreceptors are not functional till 4 days after birth and pulmonary response is also minimal. This immaturity of the homeostatic cardiovascular mechanism can cause a vicious cycle of collapse and inadequate response that becomes irreversible. Multiple cases of viruses, especially in puppies sick for longer than two weeks can have lasting heart defects.

Drug interaction with neonates can also lead to lasting effects. Again due to the inefficient filtering rate of the liver and the immature functions of the heart the rate drugs are administered to neonates becomes much more crucial. Six types of P450 isozymes drugs are most notes for lasting problems if given before the immune system is mature, these are CYP1A2, CYP2C19, CYP2C9, CYP2D6, CYP2E1, and CYP3A4—that play important roles in drug metabolism have been identified (1, 2). Of these 6 isozymes, shared metabolism by the CYP3A4 isozyme has resulted in several clinically significant drug-drug interactions. These drugs are not fully metabolized and filters leading to a build up in the system that causes high levels of toxicity, increased serum levels. And Drugs that can be metabolized by more than one isozyme have greater safety in the neonate. Also the longer a drug is used the greater the risk for lang term lasting effects.

References

Infectious Diseases and the Liver
Rohit Talwani, MD,a Bruce L. Gilliam, MD,b and Charles Howell, MDc,d Author information ▶ Article notes ▶ Copyright and License information ▶ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3660095/

Int. J. of Life Sciences, 2016, Vol. 4 (4): 451-460 ISSN: 2320-7817| eISSN: 2320-964X REVIEW ARTICLE
A review of Neonatal mortality in Dogs
Ogbu KI1, Ochai SO2, Danladi MMA3, Abdullateef MH1, Agwu EO1 and Gyengdeng JG1 1Federal College of Animal Health and Production Technology, National Veterinary Research Institute Vom, Plateau State

2Department of Microbiology, Faculty of Natural Science, Plateau State University, Bokkos, Plateau State, Nigeria 3Faculty of Veterinary Medicine, University of Maiduguri, Maiduguri, Borno State Nigeria
*Correspondence: kenike_mary@yahoo.com; +2348030852357 http://oaji.net/articles/2017/736-1486387851.pdf

Drug interactions due to cytochrome P450
Chris C. Ogu, PharmD 1 and Jan L. Maxa, RPh 1

Author information ▶ Copyright and License information ▶ Disclaimer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1312247/

Liver
Víctor M. Piñeiro-Carrero, Eric O. Piñeiro http://pediatrics.aappublications.org/content/113/Supplement_3/1097

With the amount of litter fatalities approaching 20% of the total number of puppies born each year, it is pertinent to discover if there are any pre-determining factors, like for instance,
in humans we have the Apgar scoring system that takes into account several important variables. Each variable is then individually scored on a 1-5 scale and finally all scored variables are added together for an overall score. If this overall score falls under a certain pre- determined number then the baby is flagged for more in-depth observation, and perhaps early intervention of a yet unseen problem. This is key to survival in the delicate system of a newborn. With 90%of all mortalities in neonate canines happening in the first 3 weeks of life and 60% of those in the first 10 days and with 20% of those those clustered at less than 24 hours of age, you can see the four “mortality humps” that happen. The first one at less than 24 hours of age, the second one at 3/4 days, the third one at 7-12 days and the last one at 14/16 days and if we look closer we can also see that two of these time frames also mirror the incubation time, for bacteria at 2-3 days and for viruses at 7-10 days incubation time, with a kill time after symptom onset varying greatly from a few hours to a few weeks, depending of multiples factors. This observations proves true with the majority of puppies lost at 3/4 days, as autopsy shows bacterial infection while those autopsied from puppies lost between 7-10 days often show viral infections as the underling cause and now with the primary cause of <24hours deaths being linked to identifiable factors we are continuing to win the battle for improving puppy fatality rates.

Low glucose levels and low birth weights, which also correspond to low glucose levels, overwhelmingly took the spotlight for indicating which neonatal canines may be at risk for higher mortality rates. Neonates that passed away within the first 24 hours all had glucose levels recorded within the first 8 hours of birth between 21-69mg/dl while puppies that lived past 21 days had recorded glucose levels in the first 8 hours recorded at 55-138mg/dl. Low glucose levels then lead to a lack of energy and slow body functions, which can lead to low temperature, this low temperature then slows the processes of the intestine preventing any new source of energy, or glucose from being absorbed. This is the vicious cycle of temperature and glucose in the neonate canine. Catching low glucose levels as soon as possible in neonates and supplanting them with a sugar water or nutritional syrup during the first 24 hours of life drastically increases the puppies chances of survival. Glucose levels taken at 24 hours that are below 94mg/dl are at an addition risk of death until 21 days of age.

Similarly birth weights of puppies that are 25% of the average birth weight of the litter have drastically decreased chances of survival, and puppies that do not gain 15-20% of their body weight each day for the first week should also be closely monitored and possibly supplemented, as they are also in a high-risk group. It should be noted that puppies of a larger size at birth also had higher glucose levels.

Overall the close monitoring of birth weights, temperature and blood glucose levels at birth and during the first 24 hours will give you the best opportunities to catch, treat, and provide you with the best chance of preventing any of these 1st twenty-four hour “hump” of mortalities in neonate canines. A second step to this process would be to then have the proper whelping set-up that could assist in your endeavors. You can preventing temperature loss, and even increase core temperature by having a heat lamp on for the puppies during birth, while they are suffering the most heat loss, simply from being born into a cooler environment all wet. You can also be prepared by having on hand a glucose vitamins supplant made specifically for neonates to increase low glucose levels in ‘at risk’ puppies. Also by monitoring any puppies that are less than 25% of the size of the littermate’s to ensure adequate nursing time and possible supplementation if that is not possible can very well save lives.

References

Monitoring of the newborn dog and prediction of neonatal mortality
Author links open overlay panel HannaMilaabAurélienGrelletaMarineDelebarreaClaireMarianicAlexandreFeugiercSylvieChastant- Maillarda

Show more
https://doi.org/10.1016/j.prevetmed.2017.05.005 https://www.sciencedirect.com/science/article/pii/S0167587716306468

Neonatal Mortality in Puppies Due to Bacteremia by Streptococcus dysgalactiae subsp. dysgalactiae https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1392640/

Neonatal Disease in Puppies
British Small Animal Veterinary Congress 2008
Wenche K. Farstad, DVM, Dr.Scient., PhD, DECAR
Norwegian School of Veterinary Science
Oslo, Norway https://www.vin.com/apputil/content/defaultadv1.aspx?id=3862917&pid=11254&print=1

What is a fatty acid?The official definition is – a carboxylic acid consisting of a hydrocarbon chain and a terminal carboxyl group, especially any of those occurring as esters in fats and oils. They are the building blocks, for fats, in our bodies, and there are different types. Notice that they are an acid, and it is their COOH cap that is the reason these molecules are acids. They are very familiar to an acetic acid, except they form much longer chains. In order to make a fat you need to take three fatty acids and bond then with glycerol to form a triglyceride, notice the ‘tri’ in the name, indicating the three fatty acids. The type of fatty acids that make up a triglyceride will control many attributes about the fat, such as how healthy it is, or how it looks or if it is a solid or a liquid at room temperature, these characteristics of fat will often divide them into categories of saturated or unsaturated fats. Triglycerides are one of three of the main classes of esters, the other two being phospholipids and cholesterol esters. Esters are defined as a chemical compound derived from an acid where at least one OH (Hydroxyl) group is replaced by an O (alkoxy) group. Esters are, usually, derived from carboxylic acid and an alcohol, and glycerides are fatty acids esters of glycerol. The Omega three fatty acids are derived from, you guessed it, three main different types of acids, Alpha-linolenic acid *ALA which has a 18 carbon chain, eicosapentaenoic acid *EPA which has a 20 carbon chain, and docosahexaenoic acid *DHA which has a 22 carbon chain. The DHA and the EPA are found mainly in fishes and other seafoods, while the ALA’s are mainly found in plant/nut oils like flaxseed, soybean and canola oils. Fatty acids are essential for our body and our body cannot make them, which means it needs to be consumed from an outside source. ALA’s can be processes by the body and produce small amounts of DHA and EPA but not in a significant amount, so getting DHA and EPA from foods or supplementation is necessary to maintain adequate level. Omega threes are the food for our brain, sperm and eyes and plays a huge role in brain, eye, heart, cardiovascular, immune, and endocrine health. Studies are only just now stretching the surface of the vast array of benefits derived from Omega three supplementation.

Lets first look at Cardiovascular disease and omega three’s, here we find, what at first may seem to be a web of conflicting information, but upon further examination both are supported by scientific data. This proves to be a conundrum worth exploring further. First we have key data showing that Omega threes can decrease inflammation throughout all parts of the body, it also can also decrease triglycerides, remnant lipoprotein levels, decrease rate of growth of atherosclerotic plaque, improve endothelial function, slightly lower blood pressure, decrease risk of arrhythmia and risk of thrombosis. In large scale epidemiololgic studies with coronary heat disease (CHD) in relation to omega three consumption, secondary prevention studies suggest intake of . 5-1.8 grams per day from a fish source of DHA and EPA. With suggested intake of 1.5-3 grams per day of ALA which comes from plant and nut sources. This same studio shows that 2-4 grams of EPA+DHA per day can lower triglyceride levels by 20-40%. It is also noted that Eskimo’s have a very high normal dose of Omega three over generations and this has cause many interesting traits to develop. A study in Alaska in the town of Yup’ik, Eskimos on average consumed 20 times more omega three than people in the

lower 48 states. After taking blood and measuring the concentration on DHA and EPA in the local population and then found and interesting data set. The study showed that obesity did not necessarily increase your rise of heart disease. That while most of the natives were obese, only those that had very low levels of DHA and EPA in their blood had increased blood triglycerides and c-reactive proteins *called CRP and is a measure of inflammation in the body, and it is these elements that increase the risk of heart disease. The people tested at high levels of DHA and EPA in their blood, despite being obese still tested at the same triglyceride and c-reactive protein levels as that of a ‘normal weight person’ indicating that the high omega-3 levels in the blood protected the individual from the harmful effects of obesity. It was also found that blood may have a harder time clotting at high levels of omega three intake, in the normal population, than in the Eskimos, who have existed for generations with this mainly fish diet. Another example, in a recent meta-analysis showed that omega-3 fatty acids from fish can provide a 36% reduction in an unambiguous, endpoint-death from coronary artery disease.

Now lets look at the other side. There have been many more recent randomized studies on the supplementation of oil, that have show little to no effect on cardiac effect. The analysis, in JAMA Cardiology, collected data from 10 randomized trials in people who had had cardiovascular disease or were at high risk for it. There were 77,917 people in the trials, 61% men, and their average age was 64. Studies lasted, on average, 4.4 years, and the dose of omega-3’s ranged from 226 to 1,800 milligrams a day. No matter how the researchers looked at the data, they could find no association of the supplements with lowered risk for death from heart disease, or with nonfatal heart attacks or other major cardiovascular events. Another trail, The researchers examined 79 randomized trials of omega-3 fats, of which 25 were considered highly trustworthy because they were designed and carried out well, that supported the claim of Omega three’s having no effect on heart health.

What is all of this about? How can we have two different data sets that both claim evidence to contradict each other? Well one idea is about the non regulation of supplementation through the FDA. This means that no one makes sure that what is listed on the bottles label is actually in it. Meaning that unless the studies tested all of the supplements given, for accurate levels of DHA and EPA themselves then they may have been in much less concentration than advertised, if there was any at all in the brand taken, which would not give accurate results in the study. Because in studies that took actual blood DHA and EPA levels could prove a benefit to those higher blood concentration levels. Indicating a gross oversight. As not one study that I found, that indicated no heart health benefits, used any measure of DHA or EPA blood level measurements nor did I find any indication of measuring the actual levels of DHA and EPA in the individual pill supplementation programs.

Lastly we will take a look at my own 16 year observations in using omega three fatty acids at 1TBS per day per 100-200lb body mass, over the course of 5 generations of canines. In the early years, with my first generation which I started on Omega threes at 6 and 9 months of age daily, in my first generations from these pairings I had on average 1 pup out of 2 litters that ended up having heart issues. One sire in-perticular threw 4 pups in one ‘out’ litter *meaning the female was not owned by me and omega threes were not administered at the dose I use, it was later learned that he had a heart

issue and lived till he was 6… of the puppy owners of 2 of the effected pups, who did keep their pup on high levels of omega threes and they lived till 5 and 6 years, the 2 other families that did not use the additional supplementation, lost their pups at 2 years of age in both cases. This sire had other litters prior to that at my house where the females were kept on omega threes during pregnancy and out of the other 5 breedings he had we only had three total other reported cases of heart issues in his pups. He was retired at these findings as were his daughters, but I did have two grand daughters who have now been on omega three fatty acids for two generations, that I did keep and after each had 3 total litters, not a single pup was produced with a heart issue. Actually with my very first generation of pups, with each new line I have brought in, which were produced by a mom taking omega threes for the first time in her lines, occasionally will have a heart issue pop up, but after 3 generations of moms being fed the omega threes, I have yet to have a heart issues in a pup of that next 4th generation.

Next I would like to look a infant health and development with the addition of DHA and EPA. Studies are indicating that higher levels of omega threes during pregnancy can improve brain functions. In the double blind, placebo controlled randomized study ‘Judge et al’ with consumption at 1500mg/wk found that Maternal DHA intake was associated with enhanced infant problem-solving skills but not recognition skills at 9 mo old. Another double blind, placebo controlled randomized study ‘Dunstan et al’ giving DHA at 2.2 g/d and EPA at 1.1 g/d found that at 21/2 year of age children whose mother were supplemented had significantly better scores of hand and eyes coordination. The study at Olsen done with 2.7 g/d of DHA +EPA showed that moms who had had previous preterm deliveries were better able to carry their baby to term. Another done with 2.7 g/d showed a decreased incidence of Asthma in children at 16. Actually the only studies that did not show a positive correlation in DHA and EPA were those given at lower doses like the study at Makrides which only did 800mg/d and showed no real improvement in cognitive development … but again one may want to look at the quality of the supplement used, as these are unregulated fish oil capsules used in the study, but this could also indicate a correlation with higher levels having greater than proportion benefits than that at lower levels of supplementation. My own experience with this, is that pups who have been given adequate and consistent doses of Omega threes by way of mothers consumption, are easier to potty train, and have a less distracted nature compared to pups who’s moms were not of any extra dose of omega threes. This has come by way of pups that I bring into my program and their trainability, or in other words how many lessons each pup needs before understanding what is being asked of that puppy, as well as attentiveness. Pups Brought into my program from outside breeders always take longer to potty train, sometimes being an adult and still having accidents even with a dog door present, they do not respond to verbal communication as well and take longer to learn new lessons they also have a shorter attention span, this is consistent with litters of my own. Reference one is with Cleo between her 2nd and 3rd pregnancy. During Pregnancy #2 , I had runout of Omega threes and was slow reordering and she only had them through her 2nd week, prior to embryonic implantation which occurs at around 18 days post tie. Litter two was still having potty training issues at week 8, and were very distracted pups that could not seem to calm down enough to listen. Then litter #3 we had her on the omega threes through out the pregnancy and that litter fully potty trained to a puppy door by 6 weeks

of age, they were also overall a much calmer litter of pups that all learned to sit for me by 8 weeks of age as a group. Reference two refers to three different puppies that I Brough in all from different breeders and all the same age by weeks and all brought to me during the same time frame. Two of the pups learned much faster, could calm down and listen to me and picked up our puppy door the first day we had them, while puppy #3 was wild and would not listen at all for weeks, it just seemed to distracted to listen, it also had several accidents that first week inside the house. When I contacted the breeders the two breeders that had produced the calmer, smarter pups, these two breeders who had been mentored by me and had the mothers on the omega threes during pregnancy and growth, while the third pup’s breeder had not used any omega three supplementation during pregnancy or after.

Omega threes are also essential in the formation of the retinas, the cell membrane of the eye has one of the highest concentration of DHA in the body at 50-60% DHA in the total fatty acid contend within rod outer segments of photoreceptors. These photoreceptors have the ability to constantly renew due to the amount of continues oxidative damage to the eye, this means that the eyes need a constant source of DHA for its very composition. Higher levels of DHA in the photoreceptors which number 60 to each single pigment of eye color, has a positive correlation to flexibility of the bilayer, and adopt a hairpin-like structure, which increased the interfacial area per lipid. Another interesting fact about the eyes are that they renew from the inside out, the center which has high regeneration, but then these cells pile on top of each other to add old disks at the tip which have no regeneration ability, higher levels of DHA allows for greater shedding of these old receptors/disks allowing more new and fresh re-synthesis of new membranes. With out enough DHA in he membranes, it can cause loss of membrane fluidity and function which could alter the process of the outer segments renewal. In a study that looked at depriving rats over the course of three generations found that by the 3rd generation the retinas were reduced by 55% the amounts of omega three as rats fed a normal diet, this led to sever reduction in retina sensitivity. Another study ‘Carrie at al. showed that supplementation with phospholipids rich in DHA restored retinal level of DHA and amplified the b-wave amplitude on an ERG. Dietary supplementation of DHA during aging improved the visual abilities both in the control and deficient mice. This study suggested that Omega threes could potentially reverse any retinal dysfunction that was linked with omega-3 deficiency earlier in the mouses life, even if reversal did not begin until the animals were of much older average age. Literature goes one to state that the pre mentioned anti inflammatory role that the omega threes have also play a positive role in eye health by inhibiting the formation of cyclooxygenase and lipoxygenase products of AA, this shift in the amount of omega threes results in anti inflammatory effects. High omega threes also decrease the production of platelets, and modulates the effects of C-reactive proteins, vascular adhesion molecules, intercellular adhesion molecules and homocysteine. Omegas threes also can promote vascular regrowth after injury, thereby protecting against neovascularization, which is the formation of blood vesicles, which in the eye could cause serous sight problems, and many sight -threatening diseases have a first stage where there is vessel loss, then it is followed by hypoxia-driven destructive neovascularization, basically a stress driven response to damage where new blood vessels will grow in places to increase blood supply to try and repair damage, but in

some places like the eye or the joints this can cause more damage to the area than the original injury. These findings indicate that increasing the amount of omega-3 or their bioactive products will reduce pathological angiogenesis. Omega threes were shown in a study with rats showed protection from neurotoxicity by way of ischemia, or prevention of blood from getting to the eye organ, which will poison the eye. But the rats with higher levels of DHA were quicker to recover by way of preserving the mitochondrial membranes potential and inhibiting caspase activation. Another huge plus for omega’s and the eyes are its benefits to AMD or age related macular degeneration. There is now a correlation between low DHA in the retina and early onset AMD, but the best news is that with increased consumption of omega threes, but more specifically ALAs which can be found in both fish and nuts, that these increased levels, decreased the risk of AMD progression.

Another brain benefit from Omega threes are in the areas of dementia with Alzheimers disease. Unfortunately the reverse of that is that not consuming enough omega threes can lead to an increased risk for age-related cognitive decline or dementia such as Alzheimer’s disease. With out the neuroprotective properties of adequate levels of omega three you risk not being protected from an array of factors, one of the key factors is that a diet high in omega threes with limits the production and accumulation of the amyloid β peptide toxin that is widely believed to drive the disease. Another nine epidemiological studies support increased dietary intake of fish as associated with the educed risk for cognitive decline or dementia, by a whopping 40-50%. Several studies will back up this, such as the study done in Kalmijn at al 1997, which showed an inverse correlation with cognitive decline. In the ‘Morris at al 2003’ study it showed a reduced risk with DHA but not EPA for AD. Two studies correlated a dose dependent effect these were ‘Nurk at al 2007 and Can Gelder at al 2007. The prospective Framingham study from Schaefer et al. 2006 used DHA levels in the blood, taken 10 years prior to cognitive assessment showed protection from omega three fatty acids, with an average age of 76 years old . This study show that the higher levels of DHA in the blood was predictive of lower risk, and slower decline and that no other lipid showed these predictive measures.

Is it any wonder that with all the benefits that omega three’s give the brain that now there are findings that lower levels of omega threes can lead to compounding existing brain disorders like ADHA, and certain mood disorders. Adequate levels of omega threes in the brain can lower stress levels, increase mood, and now such findings have led to the hypothesis that lack of sufficient amounts of specific fatty acids affects brain function in such a way as to cause or worsen the symptoms of ADHD.

Fish, and more importantly the omega threes in them have been show to also reduce the risk of breast and prostate cancer. At around 8 times more effective than plant based sourced for prevention. Study co-author Prof. David Ma, who currently works in the Department of Human Health and Nutritional Sciences at the University of Guelph, and colleagues recently reported their findings in the Journal of Nutritional Biochemistry. In this study the mice given fish oil derived omega 3’s experienced a 60-70% reduction in tumor size and a 30% decrease in the overall number of breast tumors present. Also if you will remember that Omega threes will help prevent the growth of new blood vessels, that same function also prevents new blood vessels to form with tumors which get their blood supply through the blood vessels that are there

to ‘heal’ them. With out the extra blood vesslies feeding the tumors they can cause decline, on top of restricting tumor cess growth high levels of omega threes have shown cancer cells to self-destruct.

With all of the amazing things that omega threes can do for our insides, some may forget how beneficial they can be to our outsides as well. Omega threes can improve completion, reduce wrinkles, lessen acne, and improve tone. This is because DHA and EPA are also incorporated into cell membranes in the the top layer of skin (the epidermis) forming a protective layer. They work on the phospholipid bilayer helping it to hold moisture and stay plumper. EPA also blocks the release of enzymes cause by sun damage, this boosts collagen and prevents lines and sagging. My own experience with skin conditions in the canine have also proven very rewarding. Skin issues of my chosen breed the Great Dane is what launched my exploration in to the omega threes back in my early youth. My first Dane female had skin acne disnogised as a staff infection, was given antibiotic after antibiotic, it would only go away briefly and then reappear and always coincide with a secondary UTI infection, after months of no results my vet provided me with my very first omega three oils. With in three days of use the ache has disappeared, within a 3 week period her hair had grown back and was shiny and soft and fuller than before I also noticed a huge reduction in shedding. Over the years my findings have been consistent. Puppies and dogs on omega three fatty acids have improved coat health, and fewer skin issues like acne, hot spots, Demodox mange, or any yeast related skin issues, than dogs not on it. I have also noticed a positive correlation with omega threes and just the shine and denseness to the coat compared to dogs not one them. My findings show that for the benefits to be received you must take an adequate amount of them. I feed 1TLB per 100-200lb even 1/2 that amount per day will be noticed with more shedding and less shine, and more skin issues within a month, and a complete stop of the omega threes will show in the hair and skin on the canines within weeks. But is also works both ways and they only have to be on them consistently for a few weeks to begin to notice the benefits agian. The one area where I have noticed long term effects of Omega three fatty acids, regardless if they are continued or not is in a 2nd plus generations that had been fed high doses of omega threes during pregnancy. Over the years and generations of puppies being on the omega threes during gestation I have noticed that I have fewer and fewer skin issues in my pups, lower cases of allergy induced responses. Ive also noticed fewer and fewer genetic defects effecting my puppies and stronger immune systems with longer lived lives, proportionally more so for the more generations a certain line has been with me, and this strong evidence is worthy of addition research.

References

KidsHealth / For Parents / Definition: Fatty Acids https://kidshealth.org/en/parents/fatty-acids.html

How Fats Work https://science.howstuffworks.com/innovation/edible-innovations/fat1.htm

Fatty acid
From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Fatty_acid

Ester
From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Ester

http://www.brainhealtheducation.org/resources/omega-3s-and-brain-health/

Omega-3 Fatty Acids
Fact Sheet for Consumers https://ods.od.nih.gov/factsheets/Omega3FattyAcids-Consumer/

Omega-3 Fatty Acids and Cardiovascular Disease
Penny M. Kris-Etherton , William S. Harris , Lawrence J. Appel
and for the AHA Nutrition Committee
Originally published1 Feb 2003Arteriosclerosis, Thrombosis, and Vascular Biology. 2003;23:151–152 https://www.ahajournals.org/doi/10.1161/01.atv.0000057393.97337.ae

Science News
from research organizations
Omega 3 supplements have little or no heart or vascular health benefit
New health evidence challenges belief that omega 3 supplements reduce risk of heart disease, stroke or death
Date:
July 17, 2018
Source:
University of East Anglia https://www.sciencedaily.com/releases/2018/07/180717194558.htm

Omega-3s and Brain Health

OMEGA-3s AND BRAIN HEALTH

Omega-3 no protection against heart attack or strokes, say scientists https://www.theguardian.com/society/2018/jul/18/omega-3-no-protection-against-heart- attack-or-strokes-say-scientists

Dietary Supplements: What You Need to Know https://www.fda.gov/food/dietarysupplements/usingdietarysupplements/ucm109760.htm

Omega 3 Benefits to the Retina https://www.enhancedvision.com/low-vision-info/eye-health/omega-3-benefits-to-the- retina.html

Histone H2AX is integral to hypoxia-driven neovascularization.
Economopoulou M, Langer HF, Celeste A, Orlova VV, Choi EY, Ma M, Vassilopoulos A, Callen E, Deng C, Bassing CH, Boehm M, Nussenzweig A, Chavakis T. https://www.ncbi.nlm.nih.gov/pubmed/19377486

PMID: 22175009 Retina and Omega-3
J Nutr Metab. 2011; 2011: 748361.
Published online 2011 Oct 31. doi: [10.1155/2011/748361] https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3206354/

What is angiogenesis and how does it play a role in cancer treatment? An ESUN Article by Karen Albritton, MD http://sarcomahelp.org/articles/angiogenesis.html

Age-Related Macular Degeneration (AMD) https://nei.nih.gov/health/maculardegen

Fish-derived omega-3 best for preventing breast cancer https://www.medicalnewstoday.com/articles/320762.php

Do Omega-3s and Antioxidants Fight Cancer? https://www.webmd.com/cancer/features/antioxidants-omega3s#1

Omega-3 fatty acids and dementia
Greg M. Cole, Ph.D., Qiu-Lan Ma, M.D., Ph.D., and Sally A. Frautschy, Ph.D. Author information Copyright and License information Disclaimer https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4019002/

Omega-3 fatty acids as treatments for mental illness: which disorder and which fatty acid?
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2071911/

How using Omega 3 fish oil for your skin can revolutionize your complexion https://www.barebiology.com/pages/guide-omega-3-fish-oil-skin

There are 8 B vitamins B1,2,3,5,6,7,9,12 of these B6 is important in immune functions and low levels are linked with inflammation in the body, and B12 is linked to energy which additional B12 may be needed to improve energy levels and encourage suckling in a fading neonate.

While Milk Thistle may be a great idea for help with lower and immature kidneys and renal function of the neonate. Especially when going through a viral or bacterial infection the already immature overworked kidneys get an over load and this combined with any Jaundice or other environmental stressors may be enough in combination to cause the eventual death of neonates, which are largely due to a combination of several interfering conditions that together work together to bring about immune failure in the neonate. Milk thistle is a powerful anti inflammatory and antioxidant herb that will protect the liver from damage and has been used for over 2,00 years for liver and gall bladder problems. Milk thistle contains sylimarin and silibinin which help to aid and protect the liver from free radical damage, because of the livers direct role in the immune system by eliminating microorganisms and preventing tumor transformation , a healthy liver can mean the difference in life and death, and so supporting the liver is a 2nd line of defense against invaders. Recent research has just been published in the “medical Science Monitor” that in vitro testing showed a proportional increase in lymphocyte proliferation to the dose of milk thistle given, this makes it an exciting candidate to help with infectious diseases and even cancers.

Goji berries specifically the ‘red’ ones are gaining popularity and are now becoming readily available as a powder, like flour for baking, in your towns grocery store. This allows for an easy tonic for administering to neonates. Gogi berries are rich in Lycium barbarian polysaccharides, these are know to enhance the bodies ability to resist disease, their chemical structure is very similar to substances found in Enchinacea and Maitake mushrooms which also support immune health. Gogi are also rich in Vitamin C, Selenium, potassium,18 amino acids 11 of which are essential, and Zinc all of which are also know to protect against disease and aid in recovery. They are also iron rich, which is unusual in a fruit, and they promote ‘good’ intestinal bacteria, as well as aid in the bodies immune system to distinguish between friend and foe and assist with cellular communication. Also a rich source of L-arginine and L-glutmine which are building blocks for immunities and help to reduce inflammation. These attributes also help to lower allergy sensitivity, and spread of cancerous cells. In studies done with animal trials they have found that the berries increased non-inflammatory immune cells that guard against bacteria and cancer, they reduced inflammation and may be helpful in treating inflammatory diseases, they also inhibited symptoms of swelling and rheumatoid arthritis and showed enhanced immunity that may also lead to improves resistance to cancer cell growth. As well as being high in numerous photochemical *the stuff that makes fruit the dark color and has many antioxginating properties. New preliminary trials show that Black goji berries have 3-8 times the nutritional value in phenolic, condensed tannin, econometric anthocyanin content as well as higher antioxidant capacities than red goji which only exceed in the highest carotenoid content and iron. But with the low availability of black goji berries the red goji berry powder is an excellent easy to find immune booster.

References

Goji Berry and Curcumin: Protecting your Immune System
Amazing Nutrients Demonstrate Ability to Naturally Boost your Immune System https://www.specificare.com/articles/immune-system/immune-power-protecting- your-immune-system

8 Healthy Facts About the Goji Berry https://www.healthline.com/health/goji-berry-facts

What are goji berries?
How Goji Berries Strengthen Your Immune System https://recipes.howstuffworks.com/goji-berry4.htm

Goji Berry Benefits: Antioxidant & Anti-Inflammatory Superfruit https://draxe.com/goji-berry-benefits/

Comparative studies on phenolic profiles, antioxidant capacities and carotenoid contents of red goji berry (Lycium barbarum) and black goji berry (Lycium ruthenicum)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5483215/

Recharge Your Body’s Defense System
Your body has an elaborate immune system that defends your body by fighting off dangerous germs and foreign intruders. Are you getting the nutrition you need to keep that immune system healthy?
Posted on 10/25/2012 https://www.doctoroz.com/article/recharge-your-body-s-defense-system

Milk Thistle and the Immune System http://healthyeating.sfgate.com/milk-thistle-immune-system-9346.html

What are the benefits of milk thistle?

Last reviewed Wed 20 December 2017
By Lana Burgess
Reviewed by Debra Rose Wilson, PhD, MSN, RN, IBCLC, AHN-BC, CHThttps://www.medicalnewstoday.com/articles/320362.php

Immune support can be fundamental in the pendulum of the neonates survival of a viral or bacterial infection. Here we will look at a few immune system boosters and the hows and why’s of the way they work.

Garlic, contains immune stimulating compounds called allicin. This promotes white blood cell activity, and stimulates immune cells to fight fungal, viral and bacterial infections. Fresh garlic has 100% effectiveness with human rhinoviruses *common cold, as well as repertory problems and even herpes! Discovery made by the Chief of microbiology, at Brigham Long university. In each Garlic clove you can find 5mg of calcium, 12mg of potassium, and more than 100 different sulfuric compounds, it is these that are highly reactive, and will break apart and form new compounds inside your body and it is in this that gives garlic its amazing infection fighting ability, so much so that fresh garlic was used to prevent gangrene in both world wars! But fresh garlic is needed as heat and water inactivate sulfur enzymes and can diminish antibiotic effects. Studies have shown that crushing garlic and letting it sit for 10 mins help it to retain its properties during cooking.

Echinacea, contains enhinacoside, a natural antibiotic also like penicillin, and it is able to kill a broad range of viruses, bacteria, fungi, and even protozoa. Another thing it contains is echinacein, a biochemical that protects against germ attack by neutralizing the tissue-dissolving enzyme hyaluronidase, produced by many germs. In addition to this it can boost T-cell production by up to 30% more than other immune boosting drugs. Echinacea also increases production of chemokine interleukin-8 and MCP-1, which promote immune cells to migrate in greater numbers to infection site. All parts of the plants contain these components but the roots contain the most. But once symptoms start it may be to late to receive full benefits of their amazing properties, some benefit is still given and it often will reduce the length of the symptoms but for maximum benefits it should be given as an preventive measure and taken to build up the immune system before symptom onset. This is largely due to echinacea tricking your body into thinking that is it an invading viral army, and your body builds up antibodies to fight it off, but then it is a non harmful invader, so the antibodies are not used on it, but are then available in greater numbers for a real infection. Because of this it is best to take it for 2-3 weeks and then take a week off as your body will begin to recognize it as a ‘false’ invader and stop building immunities reserves against it.

Vitamin C and vitmin E levels in full term neonates, median 58.1, did not develop hyperbilirubinemia while neonatal levels with, median 89.4, in the first 24 hours did develop hyperbilirubinemia. This significant finding linking Vitamin E mainly and with lesser findings vitamin C to a leading cause of Hyperbilirubinemia, this is the condition, also caused jaundice, is where to much bilirubin, a type of cell wast, is built up in the blood due to a lack of antioxidant build up, which naturally defends against it.

References

Garlic, eckenhancia, bs, c, gouge berry re vs black, black pigment photoclorides* slippery elm bark

5 Foods for Colds and Flus – Naturally Boost Your Immune System! https://healthfree.com/foods-for-flu-boost-immune.html

How Garlic Fights Colds and The Flu https://www.healthline.com/nutrition/garlic-fights-colds-and-flu

Garlic: An Immunity-Boosting Superstar
A longtime kitchen staple, garlic doesn’t just add flavor to most recipes, it’s also good for you.
By Katherine Schaufelberger https://www.webmd.com/food-recipes/features/garlic-immunity-boosting-superstar

Boosting Your Dog’s Immune System

• Dog Immune System
• / By Dana Scott
• http://www.dogsnaturallymagazine.com/boosting-your-dogs-immune-system/Vitamin C megadosage
  From Wikipedia, the free encyclopedia https://en.wikipedia.org/wiki/Vitamin_C_megadosageAntioxidant vitamins and hyperbilirubinemia in neonates
  Khalid K. Abdul-Razzak,*,1 Mohamad K. Nusier,2 Ahmad D. Obediat,3 and Ahmad M. Salim4
  https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2703239/Hyperbilirubinemia and Jaundice http://www.stanfordchildrens.org/en/topic/default?id=hyperbilirubinemia-and- jaundice-90-P02375