PROPHETOPATHY TO GLOBAL WARMIG DISEASES

IIMS 10th ANNIVERSARY CONFERANCE JUNE 15- 2010

Prophetopathysts instinctively think that the worst effect of globalwarming is the melting ice cap of the North Pole. We tend to reservethe other effects of global warming for developing nations.But now that politicians also have woken up to the fact that we'realready halfway down the path toward causing a 2 degree rise intemperatures by injecting some 520 billion tonnes into the atmosphere,it's time to reconsider. Even the richest nations are not going toescape freak weather, droughts and increases in infectious diseases.These effects are already firmly rooted and they tell us thatconditions tangibly affect all and bring the issue ever closer tohome.Peter Mertens, a UK scientist, warns that African Horse disease, avirus that's closely related to bluetongue, has a strong chance ofmaking it to Europe due to warmer temperatures. Both bluetongue andAfrican Horse disease are orbiviruses, part of the reoviridae family.Mertens, who is attached to the Institute for Animal Health in the UK,pointed out that the surprise arrival of bluetongue virus serotype 8in 2006 in Belgium and Holland ought to be a wake up call and thatEuropeans should be alert for its more deadly sibling, African horsedisease.From the routes taken by the biting midges, Culicoides imicola, whichspread the bluetongue in Northern Europe, it is clear that the virusis a tangible effect of global warming. What´s more, the disease canbe spread by labs working with bluetongue virus strains. That meansthat it is also a risk to horses in the United States.The 2006 outbreak of bluetongue took place when temperatures in TheNetherlands were six degrees higher on average than preceding years.Shortly after the midges had delivered the bluetongue virus in Hollandand Belgium for the first time ever in Northern Europe, the diseasespread in rapid pace to other European countries. It then did anothersurprising thing; it survived the 2006-2007 winter, by an unknownmechanism.Yet, that particular winter was the also the second mildest winter inNorthern Europe on record. By 2007 the disease, which affectsruminants, had still not been contained. Over 2 million ruminants,mainly sheep, were killed. Despite the huge number of fatalities,bluetongue is only a nuisance compared to African horse disease, whichis considered the most lethal infectious disease in equid, killingmore than 95% of its victims. African horse sickness was diagnosed inSpain in 1987-90 and in Portugal in 1989 and was eradicated usingslaughter policies, movement restrictions, vector eradication andvaccination. Mortality levels in bluetongue are lower than those inAfrican horsesickness (20-50%) and vaccinations are highly efficient,reducing the levels to 1-2% only.An article entitled African Horse Sickness: A Threat to the UnitedStates? in The Horse, assesses if African horse disease is endangeringthe US. The authors of the report say the biting midges are unlikelyto make it across the Atlantic. "The shortest distance from Africa tothe United States is 3,000 miles (4,830 km). To cover such longdistances, transport would need to be at high altitude (3.5 miles;6,000 m), at which air temperature is far below 32° F (0° C), andCulicoides spp. would not survive", writes William R. White, aveterinarian and Timothy R. Cordes, a National Equine Program Managerin Riverdale, Maryland. But they warn that the disease might stillfind its way in by means of lab vectors because the disease is veryclosely linked with bluetongue. Bluetongue has been around in the USsince 1948 and recent outbreaks have been reported in 18 states.There are other diseases with equally harrowing potential scenarios.The Wildlife Conservation Society (WCS) warns that future outbreaks ofavian influenza, Lyme disease, Rift Valley fever, parasites, ebola,babesiosis, cholera, plague, sleeping sickness, tuberculosis, yellowfever and poisonous algal infestations known as red tides should beexpected. The organization recently released a study in which itanalyzed how pathogens will "benefi"' most from the changes in theclimate. Entitled The Deadly Dozen, Wildlife Diseases in the Age ofClimate Change (pdf) the report predicts that there are risks forhuman health and that a large part of the risks can be studied byclosely monitoring animals and wildlife.The spread of diseases has an economic dimension which makes globalwarming, once more, undesirably tangible. Since the middle of the1990s, the costs associated with bird flu and other new infectiousdiseases have amounted to some $100 billion, numbers in the reportindicate. Steven Sanderson, the president of the WCS, says that thehealth of wild animals is tightly linked to the ecosystems in whichthey live. "Even minor disturbances can have far-reachingconsequences. Monitoring wildlife health will help us predict wherethose trouble spots will occur and plan how to prepare," SandersoncommentedHydrolysis is a chemical reaction during which molecules ofwater (H2O) are split into hydrogen cations (H+) (conventionallyreferred to as protons) and hydroxide anions (OH-) in the process of achemical mechanism.] It is the type of reaction that is used to breakdown certain polymers, especially those made by step-growthpolymerization. Such polymer degradation is usually catalysed byeither acid, e.g., concentrated sulfuric acid (H2SO4), or alkali,e.g., sodium hydroxide (NaOH) attack, often increasing with theirstrength or pH.Hydrolysis is distinct from hydration. In hydration, the hydratedmolecule does not "lyse" (break into two new compounds). It should notbe confused with hydrogenolysis, a reaction of hydrogenHydrolysis is a chemical process in which a certain molecule is splitinto two parts by the addition of a molecule of water. One fragment ofthe parent molecule gains a hydrogen ion (H+) from the additionalwater molecule. The other group collects the remaining hydroxyl group(OH-).The most common hydrolysis occurs when a salt of a weak acid or weakbase (or both) is dissolved in water. Water autoionizes into negativehydroxyl ions and positive hydrogen ions. The salt breaks down intopositive and negative ions. For example, sodium acetate dissociates inwater into sodium and acetate ions. Sodium ions react very little withhydroxyl ions whereas acetate ions combine with hydrogen ions toproduce neutral acetic acid, and the net result is a relative excessof hydroxyl ions, causing a basic solution.However, under normal conditions, only a few reactions between waterand organic compounds occur. In general, strong acids or bases must beadded in order to achieve hydrolysis where water has no effect. Theacid or base is considered a catalyst. They are meant to speed up thereaction, but are recovered at the end of it.Acid-base-catalyzed hydrolyses are very common; one example is thehydrolysis of amides or esters. Their hydrolysis occurs when thenucleophile (a nucleus-seeking agent, e.g., water or hydroxyl ion)attacks the carbon of the carbonyl group of the ester or amide. In anaqueous base, hydroxyl ions are better nucleophiles than dipoles suchas water. In acid, the carbonyl group becomes protonated, and thisleads to a much easier nucleophilic attack. The products for bothhydrolyses are compounds with carboxylic acid groups.Perhaps the oldest example of ester hydrolysis is the process calledsaponification. It is the hydrolysis of a triglyceride (fat) with anaqueous base such as sodium hydroxide (NaOH). During the process,glycerol is formed, and the fatty acids react with the base,converting them to salts. These salts are called soaps, commonly usedin households.Moreover, hydrolysis is an important process in plants and animals,the most significant example being energy metabolism and storage. Allliving cells require a continual supply of energy for two mainpurposes: for the biosynthesis of small and macromolecules, and forthe active transport of ions and molecules across cell membranes. Theenergy derived from the oxidation of nutrients is not used directlybut, by means of a complex and long sequence of reactions, it ischanneled into a special energy-storage molecule, adenosinetriphosphate (ATP).The ATP molecule contains pyrophosphate linkages (bonds formed whentwo phosphate units are combined together) that release energy whenneeded. ATP can undergo hydrolysis in two ways: the removal ofterminal phosphate to form adenosine diphosphate (ADP) and inorganicphosphate, or the removal of a terminal diphosphate to yield adenosinemonophosphate (AMP) and pyrophosphate. The latter is usually cleavedfurther to yield two phosphates. This results in biosynthesisreactions, which do not occur alone, that can be driven in thedirection of synthesis when the phosphate bonds have undergonehydrolysis.In addition, in living systems, most biochemical reactions, includingATP hydrolysis, take place during the catalysis of enzymes. Thecatalytic action of enzymes allows the hydrolysis of proteins, fats,oils, and carbohydrates. As an example, one may consider proteases,enzymes that aid digestion by causing hydrolysis of peptide bonds inproteins. They catalyze the hydrolysis of interior peptide bonds inpeptide chains, as opposed to exopeptidases, another class of enzymes,that catalyze the hydrolysis of terminal peptide bonds, liberating onefree amino acid at a time.However, proteases do not catalyze the hydrolysis of all kinds ofproteins. Their action is stereo-selective: Only proteins with acertain tertiary structure will be targeted. The reason is that somekind of orienting force is needed to place the amide group in theproper position for catalysis. The necessary contacts between anenzyme and its substrates (proteins) are created because the enzymefolds in such a way as to form a crevice into which the substratefits; the crevice also contains the catalytic groups. Therefore,proteins that do not fit into the crevice will not undergo hydrolysis.This specificity preserves the integrity of other proteins such ashormones, and therefore the biological system continues to functionnormally.