Vetreckon issue 2

VETRECKON – DIGITAL VETERINARY MAGAZINE Issue #

Pharmacorner – Working of alpha & beta agonist & antagonists

Basics of Rumenology

Veterinary Entrepreneurship – Cover Story

Many more……


VETRECKON

Vetreckon magazine is the magazine

and web/digital resource for the Indian

community of veterinary students,

teachers and field veterinarians which

provide latest up to date information

and new technology developments.

Publishing Director Sara Naqvi +91-8800939109 [email protected]

Editor Dr Ibne Ali, M.V.Sc. IVRI +91-9557907955 [email protected]

Design & Circulation

Rahul Thakkar +91-9540121922 [email protected]

CONTENTS

How alpha and beta agonists and antagonists works?

Understanding Basic Ruminology

Does anything exist like Veterinary entrepreneurship?

Urea Cycle (Krebs-Henseleit Ornithine Cycle)

Ibne Ali

Calf diarrhea is one of the major setback for present dairy industry and

main hurdle in its development. Due to multiple etiological system and

consequent poor diagnosis is the main reason for losses. Further

farmers never gave attention to calves because their feeding is costly

affair and provide returns after long time, that’s why farmers rarely

provide required amount of milk. Additionally, there is a myth that

unless placenta is shed off farmers never allow calves to suckle

colostrum. Calf diarrhea is attributed to both infectious and non-

infectious factors. Multiple enteric pathogens (e.g., viruses, bacteria,

and protozoa) are involved in the development of this disease. Co-

infection is frequently observed in diarrheic calves although a single

primary pathogen can be the cause in some cases. The prevalence of

each of pathogen and disease incidence can vary by geographical

location of the farms, farm management practices, and herd size.

Although the dairy industry has made great improvements with herd

management, animal facilities and care, feeding and nutrition, and

timely use of bio-pharmaceutics, calf diarrhea is still problematic due

to the multi-factorial nature of the disease. Prevention and control of

calf diarrhea should be based on a good understanding of the disease

complexities such as multiple pathogens, co-infection, environmental

factors, and feeding and management during the calving period

before disease outbreaks. Numerous infectious agents have been

implicated in calf diarrhea. Bovine practitioners and cattle producers

are aware of many enteric pathogens because these primary agents

have been known to be involved in calf diarrhea for several decades

and still greatly influence current cow-calf operations. Ten different

enteric pathogens are recognized as either major (BRV, BCoV, BVDV,

Salmonella spp, E. coli, C. perfringens, and C. parvum) or emerging

(bovine caliciviruses and BToV) pathogens. Cryptosporidium parvum

is a protozoan parasite that is frequently associated with

gastrointestinal tract disease in humans and neonatal cattle. Calves

infected with C. parvum can be asymptomatic or develop severe

diarrhea with dehydration. I hope in further issues of VETRECKON I

try to bring more elaborated information on this topic and help you to

combat this situation more efficiently.

From the desk of editor

mailto:[email protected]



VETRECKON SUBTITLE | Issue # 2 3

How alpha and beta agonists and antagonists works?

IN THIS ISSUE

mine substances that cause physiologic responses similar to those evoked by the endogenous

adrenergic mediators (neurohormones) epinephrine and norepinephrine are known as adrenergic drugs. They are referred to as sympathomimetic agents because their pharmacologic effects mimic sympathetic nervous system activity. Most clinically relevant adrenergic agonists exert their principal pharmacodynamics actions through receptor activation. Just the opposite, adrenergic receptor antagonists prevent receptor activation and thereby reduce sympathetic activity. “Sympatholytic,” “adrenolytic,” and “adrenergic blocking” are terms used to describe pharmacologic effects that, in general, simulate a decrease in adrenergic nerve activity. These terms are not synonymous, and they have been used to describe different types of antiadrenergic actions.

Adrenergic (sympathomimetic) drugs

Pharmacologic effects of sympathomimetic amines are mediated by activation of adrenergic receptors of effector cells innervated by the sympathetic nervous system. Non innervated (means which are not attached to nerve fibres) adrenoceptors also are present in some cell types. In general, therefore, pharmacologic effects of adrenergic agonists can be equated to physiologic effects resulting from increased sympatho-adrenal discharge. A thorough understanding of basic adrenoceptor concepts is important to the future practitioner

because this information has direct application to the clinical use of all adrenergic agonists and antagonists.

Adrenergic receptors

Adrenergic receptors (i.e., adrenoceptors) are macromolecular structures localized on or within the surface membrane of cells innervated by adrenergic neurons (and certain non-innervated cells). The basic physiologic function of the adrenergic receptor is to

recognize and interact with the endogenous adrenergic mediators norepinephrine and epinephrine. This interaction triggers a series of complex intracellular events that yield a characteristic change in effector cell activity.

A classic simplification of the complex field of adrenergic receptors was formulated by Ahlquist in 1948; he proposed the existence of two basic types of adrenergic receptors, which he designated as alpha (α) and beta (β). This classification system is based on the relative potencies of several adrenergic

agonists to elicit excitatory and inhibitory effects in different tissues.

Structure-activity relationships

Several factors have complicated determination of optimal structural requirements for adrenergic drugs. Most adrenergic drugs affect both α and β receptors, and the ratio of α and β activity varies tremendously between drugs and species. Some adrenergic agents cause indirect effects mediated by release of

endogenous norepinephrine. Despite these various and often conflicting interrelationships, some general and

some rather specific aspects of the

structure-activity relationship of

sympathomimetic amines have been determined.

The basis for sympathetic-like activity of various drugs depends upon the similarity of their chemical structure to that of the endogenous adrenergic mediators norepinephrine and epinephrine. The nucleus of this chemical structure, β-phenylethylamine, is a benzene ring and an ethylamine side

A

Figure 1: α = α receptor; β = β receptor; A = allergic reactions; B = bronchodilator (β2 receptor); C = cardiac stimulation (β1 receptor); CNS = central nervous system excitation; D = dopamine may interact with α, β1, and dopaminergic receptors; I = indirect-acting, causes release of endogenous norepinephrine that acts on α and β receptors; K = renal vasodilation (dopaminergic receptors); P = pressor activity; Rb = reflex bradycardia from pressor activation of baroreceptor-vagal reflex.


chain. Substitution may be made on the aromatic ring, on the α and β carbons of the side chain, and on the amine moiety.

The chemical structures and related pharmacologic characteristics of several adrenergic drugs are summarized in table below. Epinephrine, norepinephrine, dopamine, and isoproterenol have a hydroxyl group on both the 3 and 4 positions of the benzene ring. Because 3, 4-dihydroxybenzene is also known as catechol, sympathomimetic amines containing this nucleus are termed catecholamines. In general, the catechol nucleus is required for maximum α and β potencies. Removal of one or both hydroxyl groups from the aromatic ring especially reduces β activity; e.g., phenylephrine is identical in structure to epinephrine except for the lack of one hydroxyl group on the ring (Table). Phenylephrine is almost exclusively an α agonist, whereas epinephrine is a mixed α-β agonist. Substitution of a ring hydroxyl group similarly reduces potency and may actually yield an antagonist (i.e., an adrenergic blocking drug such as the β blocker dichloroisoproterenol). Substitution on the β-carbon atom of the side chain results in less active central actions in relation to peripheral effects. Substitution on the α-carbon atom yields a compound that is not susceptible to oxidation by monoamine oxidase (MAO).

Alkyl substitutions on the amino moiety affect the ratio of α- and β-agonistic properties. Within limits, increasing the size of the aliphatic substitution increases β activity. Epinephrine (N-methylnorepinephrine) is a more potent β agonist than norepinephrine. Isoproterenol (N-isopropylnorepinephrine) is a more potent β agonist than epinephrine or norepinephrine. Naturally occurring norepinephrine and epinephrine are in the levo configuration at the β-carbon atom. Dextrorotatory substitution on the β carbon yields the many times less potent d-isomers.

Adrenergic receptor subtypes: pharmacologic applications.

Historically, the principal events responsible for information transmission

across noradrenergic neuroeffector junctions were believed to include only the following: biosynthesis and storage of norepinephrine in the neuron terminal; exocytotic discharge of norepinephrine from the neuron; activation of effector cell α- or β-adrenergic receptors by released norepinephrine; and active “reuptake” of a portion of the free norepinephrine back into the axon terminal, thereby decreasing transmitter availability at the postjunctional receptors. We now know, however, that α- and β-adrenergic receptors of effector cells exist as subclasses and, furthermore, that several types of receptor-linked mechanisms operate within the adrenergic nerve endings themselves.

Prejunctional α Receptors.

The α-adrenergic receptors on the sympathetic neuron are believed to be important physiologically and pharmacologically; they subserve an autoinhibitory regulation of norepinephrine release mechanisms. The physiologic role of α-receptor prejunctional events is envisioned as a local servomechanism through which norepinephrine can govern its own release once a threshold concentration of transmitter has been exceeded within the junction.

Prejunctional β Receptors.

Epinephrine also can activate the pre-junctional auto inhibitory α receptors, with potency about equal to that of norepinephrine. Interestingly, however, low concentrations of epinephrine actually accelerate norepinephrine release. This facilitatory action is shared by the β agonist isoproterenol and prevented by β-blocking drugs. These findings indicate that noradrenergic nerve endings possess β receptors that subserve a stimulatory effect on transmitter release mechanisms, an action opposite to that of the prejunctional α receptor.

Norepinephrine itself seems to have little influence on the prejunctional β-autostimulatory receptors, perhaps because this receptor population is more

representative of β2 rather than β1 subtype. Thus the α-controlled autoinhibitory cycle probably dominates during usual communication between neuron and effector cell. A model of noradrenergic neurohumoral transmission incorporating prejunctional α and β receptors is presented in Figure, along with representative effector cells, their prototypical receptor classes, and associated physiologic responses.

Adrenergic Receptor Classification.

The original differentiation of adrenergic receptors into the two main classes, α and β, was based mainly on the relative potencies of the agonists norepinephrine, epinephrine, and isoproterenol in eliciting excitatory or inhibitory effects in a series of tissues (e.g., heart, vasculature, lungs).

The excitatory β receptors of the heart represented an important exception to this rule and pointed toward different types of β receptors, named β1 and β2. Later, α-receptors were likewise separated into α1 and α2 subtypes. Since then, virtually all receptor types have been categorized into many receptor subclasses with somewhat different pharmacodynamics profiles. This text will focus on the primary receptor types until clinical relevance has been determined for the plethora of receptor subtypes now discovered.

β1- β2 Adrenergic Receptor Subtypes: Partly because of the potent β-stimulatory properties of norepinephrine in some tissue (e.g., the heart), but not others (e.g., the lungs), it was suggested that β receptors actually comprised a heterogeneous population of two distinct subtypes: β1 and β2. Many tissues contain both β1 and β2 receptors in various ratios, depending on species and other variables. One subtype usually dominates and provides the tissue and organ with their functional classifi cation


as being under either β1- or β2-receptor control. A compilation of the predominant β-receptor subtype in several tissues.

Cardiac b1 Receptors. The functionally prevalent β receptor in the myocardium of most if not all mammalian species is the β1 subtype. These receptors are activated in the following order of potency: isoproterenol > epinephrine > norepinephrine. Activation of cardiac β1 receptors leads to the characteristic sympathomimetic response of the heart as schematized in Figure. In brief, this entails positive inotropic effects (increased contractility), positive chronotropic effects (increased heart rate), positive dromotropic effects (accelerated conduction of the cardiac impulse), and emergence of latent pacemaker activity.

Increased heart rate and contractility lead in turn to increased myocardial oxygen demand and metabolic coronary vasodilation.

Pulmonary and Vascular Smooth Muscle β2 Receptors. The β-adrenergic

receptors of the pulmonary airways and peripheral vascular beds are mainly the β2 subtype. These receptors are activated potently by isoproterenol and epinephrine but quite poorly by norepinephrine. The β2-pulmonary receptors subserve relaxation of bronchiolar smooth muscle and its accompanying bronchodilation, leading to an improvement in airway conductance. Vascular smooth muscle β2 receptors are present in various tissues, where they mediate vasodilation and reduced vascular resistance. Although there is some uncertainty, most β2-vascular receptors are probably noninnervated and, as with the pulmonary β2 receptors, depend mainly on circulating epinephrine for activation and basal adrenergic tone.

a1-a2 Receptor Subtypes. Alpha receptors also can be divided into two distinct subpopulations: α1 and α2. This nomenclature began with the realization that the pre-junctional α-receptor population responded to drugs somewhat differently than did the usual α receptors of effector cells. This led to

classification of the typical effector cell α receptor as α1 subtype, while the nerve terminal receptor was designated as α2.

Alpha2 receptors are not restricted anatomically to neuronal elements. They also are located on some non-innervated cell types, e.g., thrombocytes. Moreover, α2 receptors also share certain tissue and functions with the α1 subgroup. Pressor responses mediated by norepinephrine and epinephrine, e.g., involve activation of α1- and α2-receptor types in vascular smooth muscle. The α1 receptor represents the innervated vascular receptors, whereas the α2 type in this tissue is believed to localize predominantly in extra synaptic regions of vascular smooth muscle cells.

Endothelial cells of blood vessels also have α2 receptors, which subserve release of endothelium-derived relaxing factor (EDRF) leading to vasodilation. EDRF has been identified as nitric oxide or a closely related compound that releases nitric oxide Based on the foregoing summary of α1-α2 and β1-β2 receptor subtypes and respective tissue responses, it should be apparent that all adrenergic drugs do not necessarily produce identical effects. Their pharmacologic profiles vary depending upon their basic chemical structure and resulting activities as α, β, or mixed α-β agonists. Nevertheless, sympathomimetic amines exhibit many similar pharmacodynamic properties. Therefore, only representative adrenergic drugs will be examined in detail; other agents will be compared in relation to differences they may exhibit in agonistic properties (i.e., activity at α or β receptors) and in mechanisms of action (i.e., direct- or indirectacting sympathomimetic activity).

To be continued in next issue…..

Figure 2Schematic diagram of peripheral noradrenergic neuroeffector junctions with a model axon terminal varicosity on the left and typical effector cells on the right. The predominant adrenoceptor subtypes and associated physiologic responses of the heart, blood vessel, and bronchiole are depicted. Norepinephrine (NE) released from the neuron can interact postjunctionally with innervated α1 or β1 receptors of effector cells and perhaps overfl ow (dashed line) to other nearby postjunctional receptors. NE also can activate prejunctional α receptors (α2 subtype) to inhibit further release of NE. NE is removed from the junctional cleft by diffusion, extraneuronal uptake, and active uptake (reuptake) into the neuron, where it is metabolized by monoamine oxidase (MAO) or reincorporated into storage vesicles. Prejunctional β receptors (β2 subtype) subserve a facilitatory effect on NE release, but it is questionable (?) whether NE itself activates this β2-autostimulatory feedback loop. NE also has little β2-agonist activity in blood vessels or bronchioles, whereas epinephrine (Epi) can activate all types of α and β adrenoceptors. MVO2 = myocardial oxygen demand


Understanding Basic Ruminology

By Dr. Abdul Qadir, Tehran

The forestomach of the ruminants can be divided into primary structures, reticulorumen and omosabomal are separated by reticuloomasal orifice. The reticulorumen of an adult cow occupies almost the entire left half of the abdominal cavity and has capacity of up to 90 kg of digesta.

The establishment of rumen microbes in newborn animals requires contact with older animals at least 1-2 weeks. Live weight gain is improved by greater digestibility accompanied by higher level of VFA, also higher ammonia level which indicate a greater protein digestion by rumen microbes.

The ciliates represent 2% of the weight of the rumen content and increase in their number two times within about one day by means of binary fission in the rumen, the almost same number of increased ciliates flows to the posterior alimentary tract of the host and digested in the abomasum and small intestine as nitrogen nutrients. The bacteria and

protozoa provide the ruminant with cellulose digestion, protein and non protein nitrogenous utilization, essential amino acids, synthesis of vitamin B and detoxication.

The cellulytic Gram negative bacteria ferment carbohydrates producing acetic, propioic and butyric volatile fatty acids. The normal pH of the rumen ingesta is 6-7 and maintained by alkalinity of saliva, alkaline feed, buffering action of rumen ingesta and by elimination of acids from rumen by passage posteriorly. However increase or decrease ruminal pH resulting of indigestion. The animal control over the fermentation process by selecting the feed, adding a buffer like saliva, continous agitation and mixing the forestomach content. Retention of ingesta in the rumenoreticulum for one to three days allows sufficient time for bacterial disintegration.

Bacteria obtain adequate nutrient from

their hydrolysis of the plant feeds.

Digestion of the feed stuffs in the

reticulorumen occurs by microbial

fermentation. The mucosal epithelium

absorbs and exchanges products of the

fermentation without secretory function.

Forestomach fermentation depends on:

(1)Amounts and types of ingested feed and

water.

(2)Buffering of saliva to counteract the acidity

of the fermentation products.

(3)Eructation of the gases produced by

fermentation.

(4)Reticuloruminal motility to provide mixing;

rumination, remastication and passage of

ingesta.

(5)Rumen temperature and exchanges of

electrolytes and volatile fatty acids across the

rumen wall.

Abnormalities of any one of these functions

can lead to digestive disturbances. Ruminal

motility is used as an index of digestive

function in the ruminants. Ruminal ingests

divided into upper layer of free gas, lower

layer of fluid containing gas bubbles and

suspended food particles but the undigested

fibers float on the top.

Omasum

Dilatation of omasal

canal

Contraction of

omasal

canal

♦Transport of feed

Contraction of

omasum

♦Contents

squeezed. SlowContraction of

omasal canal.

♦Emptying of

omasal canal.

Reticulorumen

Two contractions of reticulum and reticuloruminal fold

* Reticular contents pass over reticuloruminal fold into rumen.

Contraction of ruminal atrium, dorsal blind sac and ruminal pillar.

Movement of reticular fluid over reticulorumin fold into relaxed rumen.

*Passage of coarse particles over the ruminal pillar into dorsal blind sac.

*Movement of dorsal sac results in squeezing and mixing of solid

Contraction of ventral sac and pillar of rumen with relaxation of dorsal sac.

* Fluid part of rumen contents returns to dorsal sac and ruminal atrium

and is forced through the fibrous matter.

Contraction of dorsal sac and pillar of rumen.

♦Transfer of accumulated gut contents to the cardia resulting in

eructation.

Reticular contraction prior to stage 1.

Reticular bolus projected into mouth.

Ruminal

Cycle

Stage 1

Result

Stage 2

Result

Stage 3

Result

Stage 4

Result

Eructation


1. Unlawful or criminal killing of animals through administration of poisons is known as ______

2. Unintentional addition of toxicants or contaminants to feed and water is known as _______

3. Man-made sources of toxicants are referred to as______________ sources.

4. Genetically determined abnormal reactivity of an individual to a chemical is known as

___________.

5. Failure to elicit a response to an ordinary dose of a substance due prior exposure is known as _____________.

6. The phenomenon in which toxic substances elicits beneficial effects at low doses is known as ________________.

7. For which of the following route of exposure, pre-systemic elimination is possible?

a. Oral b. Inhalation c. Intramuscular d. Intravenous

8. In the event of irreparable injury, the cell undergoes a process of programmed cell death known as__________.

A substance is classified as extremely toxic if the lethal dose (LD) is LESS THAN _____mg/kg and as practically non-toxic if the LD is ______5 g/kg.

10. The ability of a substance to induce cancer is known as ________________.

11. The common process involved in the absorption of xenobiotics across the cell membrane is _______________.

12. In body, heavy metals such as mercury, lead, cadmium tend to accumulate in ___________ (organ of the body).

13. Organo-chlorine insecticides such as DDT tend to accumulate in ____________ (organ of the body).

14. Arsenic tends to accumulate in _____ and ________ (organ of the body).

15. Major route of excretion for xenobiotics is ______________.

16. Ninety-nine percent of the molecules inside living cells are ____ molecules.

17. All non-essential lipids can be generated from ______.

18. Mammalian proteins are largely composed of ____ standard amino acids.

19. At physiologic pH, most amino acids exist as ______.

20. Cystine covalently links different regions of polypeptide chains with ______ bonding.

21. The ____(D/L) form of amino acids is found in most mammalian proteins.

22. ______ and _____ are needed for elastin formation.

23. ________ is an essential amino acid for cats.

24. The most abundant protein in the mammalian organism is:

a. Myosin b. Albumin

c. Actin d. Collagen

25. Vitamin C is required in the formation of which modified amino acid below?

a. Methylhistidine

b. Hydroxyproline

c. Desmosine

d. Homoserine

26. Urease:

a. Is a urea cycle enzyme found in liver tissue.

b. Is also known as arginase.

c. Is a proteolytic enzyme secreted by the exocrine pancreas.

d. Is an enzyme found in microbes of the rumen.

27. Match the following

Drug Target Enzyme

1. Allopurinol a. COX 2

2. Aspirin b.Xanthine Oxidase

3. Methotrexate 3.c.Dihydrofolate Rreductase

4.Tolfenamic

acid

d. Thymidylate Synthase

5. 5-Fluorouracil e. COX - 1,2

Note for students: This initiative have been taken for students who are preparing for JRF, SRF, NET, ARS, ICMAR and other such exams. I request to all of the readers to contribute in the collective effort to make it more beneficial and fruitful. You can send memory based questions that came in ICAR JRF, ARS, SRF or other exams. Please send your contribution to following email id.

[email protected]



his question is most ignored and uncategorized in veterinary education and its

associated system. One can hardly heard about any startup company begin by any skilled veterinary graduate. Many pro and against arguments may be given by intellectuals but hardline comparison with other sectors cannot be done on just superficial achievements. Since independence agriculture sector remain the backbone of rural economy at least, which drives life of nearly 90% of rural population. Animal farming like dairy, poultry and goat are main assets kept by farmers besides growing crops.

Livestock and poultry are highly integrated into the economic activities of rural people and any improvement in production of such animals will directly impact the economic status of rural people. Since beginning of dairy revolution initiated by Sardar Vallabh Bhai Patel in Gujarat many successes have been registered in different fields of agriculture and allied sectors. These achievements are legendarily known as white revolution, green revolution, blue revolution, yellow revolution and list is ever growing. Two very famous names has always been remembered one of Dr Swaminathan for green revolution and other of Dr Vargeshe Kurien for white revolution. They have brought the system in and infuse western knowledge and science in desi conditions.

Other notable personalities with strong agriculture entrepreneurship drive was Dr BV Rao, also known as father of Indian poultry industry and Shri B. Saundarajan, who gave the

system of integration in poultry production, Er. Shri Vinod Kapur of Keggs farm, who went a way around and developed a new chicken breed called kuroiler. I personally admired from Mr Vinod since I took

admission in B.V.Sc in 2006 because in this year his business model was presented as case study in Harvard Business School. What change he

brought in society is a matter of investigation I left for my readers. There are endless examples of entrepreneurs who bring livestock sector to new heights of success and development and ultimately these

enterprises bring prosperity among rural masses and brighten the rural economy.

To my surprise nobody of these

revolutionaries was veterinarian and of course I agreed that being a vet was not an eligibility to do these businesses. But could we able to question ourselves that these things wouldn’t be accomplished without an extra active participation of field veterinarians. Even veterinarians put their all efforts without any recognition. One can put a counter argument that veterinarians believes in work and people welfare without any greed of prestige and recognition. For those I would like to say that famous personalities of any profession gave name and acknowledgement to profession than only other people get mesmerized and want to choose that profession so that profession progresses.

We cannot hide from the fact that most of the people who take admission in veterinary science are those who didn’t qualify for medical

T

Does anything exist like Veterinary entrepreneurship?

by Dr. Ibne Ali,

Figure 2 Vinod Kapoor , begins his social

enterprise in 1990s which is now become huge

social success


seat. For example, music reality shows are very popular now a days and lacs of youth gave audition to be selected in these shows, what thing attracts them for such profession. Most of the people who compete in these shows are greatly influenced by lavish lifestyles of celebrities.

So, profession get respect due to the persons who are professing the profession. One of the most famous achievement Embryo Transfer Technology, successfully implemented by award winner scientist and academician Dr, ML Madan, which could have huge potential to become startup idea for institutions but it was buried after its whimsical success. This technique was so technical and sophisticated that it can’t be done by other persons except veterinarian. ETT could change the face of buffalo productive performance many times if applied on commercial basis. No doubt that this is very sophisticated technique and require much expertise and well equipped labs. Our institutions are full of these facilities and if not than government can easily sanction such facilities on demand because it is related to the development of poor masses.

Figure 3 Soundararajan and his brother introduced the concept of contract farming in poultry in Tamil Nadu in 1990

Although ETT is very common in European countries and even in Brazil, where they have developed Brahmin cattle of Indian origin and other cattle breeds of temperate

climate with this technique. This means it was not impossible to make this technique commercial. There is little fault of government as such, because government and its employees can’t work for enterprise profit and should only work for farmers’ welfare. But counter arguments throws light on it by saying that welfare of farmers can’t be achieved without commercialization of technologies.

One more notable name, Dr. S.K. Ranjan, who dedicate years of hard work and dedication in the field of animal nutrition and brought first

feeding standards for Indian livestock and poultry. After retirement he joined one meat export company at prestigious position. Under his supervision and guidance that company achieved greater heights of success. He introduce a concept of contract farming in Aligarh, where farmers was involved contract farming in which they grow buffalo calves for Hind Agro. Rural masses was involved in this and earn handsomely in this system. It is not just the question of earning money but it have very broader impact on overall lifestyle of present and coming generation. For young veterinary students it should be keep in mind that veterinary field is absolutely unexplored ocean of

opportunities. It just require patience and calibrated sincere approach towards goal. There are numerous openings where young blood can explore their heightened future with promising returns and self-satisfaction. One of the area is pregnancy diagnosis in farm animals, a kit could have been made and commercialize. Other areas are like commercialization of ETT, animal stress determination kits, stem cell therapy, pet nutrition etc. Nevertheless, these things cannot be happen without government support, Government should provide

logistics like labs and other financial assistance in PPP mode.

Veterinarian needs to be daring and get ready to take risk in new areas. Students must have to come out from the game of safe play and at the same time government should stand besides new startups to encourage the students to become entrepreneurs. Self-reliance is necessary this make our youth pro poor and accountable for their activities. Economic parlance will also get settled and new energy would come out which gives a new light to glow our noble profession Veterinary and that’s how a veterinary entrepreneur is created.

Figure 4 Moti Lal Madan, DVM, Ph.D. (Left) is an Indian biotechnology researcher, veterinarian, academic and administrator.


By Dr Neha Chahutrvedi, MVSc, Biochemistry

Although amino acids are metabolized extensively throughout the body, urea synthesis occurs primarily in the liver, with minor amounts also formed in astrocytes of the brain. In ureotelic animals, urea is the primary form in which nitrogen appears in urine. The two primary pathways by which nitrogen is transferred from amino acids to urea involve transamination and deamination reactions. Transaminases channel amino groups from several amino acids into glutamate (Glu), which can then be deaminated by glutamate dehydrogenase (GLDH), or the amino group can be transaminated onto oxaloacetate (OAA), thus forming aspartate (Asp) and a-ketoglutarate (a-KG). Carbon dioxide (CO2 in the form of bicarbonate, HCO3-), the ammonium ion (NH4+) generated from deamination of glutamine (Gln) or Glu, or from ammonia (NH3) entering directly from portal blood, and Asp now become substrates for hepatic urea synthesis. The overall stoichiometry for the urea cycle (also known as the Krebs-Henseleit ornithine cycle), can be described by the following equation:

The concentration of NH3 in portal blood is usually high following a protein meal, and it may be transiently increased by the release of additional NH4+ from hepatic glutaminase and GLDH activity. Ammonia is an allosteric activator of glutaminase. However, by the time hepatic portal blood reaches the systemic circulation, the NH3 concentration has usually been reduced by about 50-fold. Different hepatocytes lying along the sinusoid have different complements of active enzymes. Periportal hepatocytes, located near the portal vein, are the first

liver cells to receive blood from the intestine, and they are rich in carbonic anhydrase (CA), glutaminase, GLDH, and urea cycle enzyme activity. Bicarbonate generation in these hepatocytes is dependent upon CA activity, which in turn is influenced by the acid/base status. During periods of metabolic acidosis, for example, hepatic portal CO2 and HCO3 - concentrations decrease, and the low pH environment inhibits activity of hepatocellular CA and glutaminase, thereby limiting substrate availability for the urea cycle. The five reactions required in periportal hepatocytes for urea formation are depicted in. The first two occur in mitochondria, and the last three in the cytoplasm. Starvation or an increased protein intake can alter concentrations of individual urea cycle enzymes 10- to 20-fold. Carbamoyl Phosphate Formation Mitochondrial carbamoyl phosphate formation, the first and also rate-limiting reaction in the urea cycle, is catalyzed by carbamoyl phosphate synthetase-1 (CPS-1). A CPS-2 exists in the cytoplasm, however, it uses a different nitrogen source, and participates in pyrimidine nucleotide rather than urea biosynthesis (see Chapter 14). N-Acetyl glutamate, whose steady state level is determined by the rates of its synthesis from acetyl-CoA and Glu, is a cofactor required as an allosteric activator of CPS-1. Under the influence of CPS-1, HCO3-,NH4+, 2ATP and H2O are condensed in the formation of carbamoyl phosphate, 2ADP, and an inorganic phosphate (Pi). Citrulline Formation The second reaction, catalyzed by ornithine transcarbamoylase, involves mitochondrial condensation of carbamoyl phosphate with ornithine, thus forming citrulline and Pi. A citrulline-ornithine antiporter, which transports ornithine into mitochondria in exchange for citrulline, is located in the inner mitochondrial membrane. Both ornithine and citrulline are basic amino acids, and citrulline can also be formed in mucosal cells of the gut.

Argininosuccinate Formation The third reaction, catalyzed by argininosuccinate synthetase, involves cytoplasmic condensation of citrulline with aspartate, thus forming argininosuccinate. Linkage occurs via the a- amino group of aspartate, which ultimately provides the second nitrogen of urea. Energy required for this condensation is provided by the hydrolysis of ATP to AMP and 2Pi, and

Overview

Urea synthesis occurs primarily

in the liver.

• Portal-caval shunts and acquired

or inherited defects in urea cycle

enzymes promote

hyperammonemia.

• Aspartate serves as a nitrogen

donor in the cytoplasmic phase of

hepatic urea formation.

• Mitochondrial carbamoyl

phosphate formation is rate-

limiting in hepatic urea formation.

• A mitochondrial citrulline-

ornithine antiporter exists in the

inner mitochondrial membrane of

periportal hepatocytes.

• Fumarate, generated in the

cytoplasmic portion of the urea

cycle, can either be reutilized

therein, or it may leak away into the

TCA cycle.

• Urea nitrogen is used by rumen

microbes for protein biosynthesis.

• Arginase is a liver-specific

enzyme.

• Taurine is essential amino acid in

cats.


this reaction can also occur in the kidneys. Arginine and Fumarate Formation The fourth reaction (which can also occur in the kidneys), catalyzed by argininosuccinase, involves cleavage of argininosuccinate into arginine and fumarate (i.e., the carbon skeleton of aspartate). Fumarate now forms a link with other pathways, including cytoplasmic reformation of aspartate, or entry into the mitochondrial tricarboxylic acid (TCA) cycle. Fumarate is hydrated to form malate in the presence of fumarase, an enzyme found in both mitochondria and the cytoplasm of liver cells. The malate so formed may be shuttled into mitochondria to enter the TCA cycle, or it may be converted to pyruvate {by malic enzyme (ME)} or oxaloacetic acid (OAA) {by malate dehydrogenase (MD)}. The OAA may then undergo transamination by accepting an amino group from Glu to reform aspartate (see Chapter 9), thus completing an entirely cytoplasmic transamination route for entry of nitrogen into the urea cycle. Urea Formation The fifth reaction, catalyzed by cytoplasmic Mn++-containing arginase, involves removal of the urea side chain from arginine, thus forming ornithine, which is then transported back into mitochondria to undergo another cycle of urea biosynthesis. Urea, being sufficiently lipophilic and, unlike NH3, a nontoxic end product of mammalian metabolism, diffuses out of periportal liver cells into blood. Disposal of Urea The blood urea nitrogen (BUN) pool is freely filtered by the kidneys, with about 50% of that filtered being normally reabsorbed into blood. The other 50% is normally excreted into urine. The high BUN levels that often occur in patients with kidney disease are generally considered to be a consequence, not a cause, of impaired renal function.

Although approximately 75% of the BUN pool is ultimately excreted through urine, about 25% normally moves into the digestive tract where bacterial urease activity is high. The NH3 formed can be funneled into bacterial protein synthesis, or be absorbed directly into the hepatic portal circulation. Urea enters the reticulorumen through salivation, or directly from the circulation, and it also diffuses across mucosal cells of the colon. That entering the rumen endogenously each day is equal to about 12% of normal daily dietary nitrogen intake. Rumen microbes are capable of synthesizing all essential and nonessential amino acids for their own protein biosynthetic purposes. This can occur from nonprotein nitrogen (NPN, such as urea), and appropriate hydrocarbons (from cellulose). Ruminant animals can grow, reproduce, and lactate, although not at optima. Dietary protein is generally required, however, for optimal growth and

function. Due to high bacterial urease activity in the rumen, the [NH3] there usually ranges from 5 to 8 mg/dl (mg%). Since NH3 is a buffer {i.e., it can accept a proton (H+)}, excess urea can raise the [NH3] of rumen fluid, thus causing it to become more alkaline. Therefore, too much dietary protein or urea can lead to a metabolic alkalosis in ruminant animals, and make it more difficult for the rumen wall to absorb volatile fatty acids (i.e., butyrate, propionate, and acetate) produced through microbial cellulose digestion. These essential metabolites are more readily absorbed when in the unionized, free acid form. The normal rumen pH range is 5 to 7.

Abnormalities in Urea Biosynthesis Certain liver diseases that affect the urea cycle, particularly acquired or inherited defects in any one of the five urea cycle enzymes, may have severe consequences for the mammalian organism since there are no alternative pathways for urea biosynthesis. For example, arginosuccinate synthetase deficiency, although rare, has been reported in dogs. Patients exhibit protein intolerance, hyperammonemia, and a hepato-encephalopathy which leads to CNS depression, coma, and death if left untreated. Treatment generally requires measures to control the hepatoencephalopathy, including a low-protein diet and oral antibiotics. Vascular abnormalities that shunt portal blood into the systemic circulation without perfusing hepatic sinusoids (i.e., portal-caval shunts) compromise the liver's ability to detoxify NH3 through the urea cycle, and many other liver diseases are known as well to result in decreased urea cycle enzyme activity with

hyperammonemia. Cats with arginase deficiency, or those fed diets low in arginine, generally require more dietary ornithine. Arginase is liver-specific since it is restricted to the urea cycle, and when it leaks into blood following hepatocellular damage it is usually cleared from the circulation faster than the transaminases (ALT and AST). Therefore, a decrease in the serum activity of this enzyme can sometimes be a useful prognostic indicator of liver cell regeneration following acute liver injury.


Interesting Animal Facts Gorillas can catch human cold and other illnesses.

A newborn Chinese water deer is so small it can almost be held in the palm of the hand.

Ostriches can run faster than horses, and the males can roar like lions.

A lion in the wild usually makes no more than twenty kills a year.

The female lion does ninety percent of the hunting.

The only dog that doesn’t have a pink tongue is the chow.

Turtles, water snakes, crocodiles, alligators, dolphins, whales, and other water going creatures will drown if kept underwater too long.

Almost half the pigs in the world are kept by farmers in China.

On average, dogs have better eyesight than humans, although not as colourful.

Deer have no gall bladders.

There is an average of 50,000 spiders per acre in green areas.

Snakes are carnivores, which means they only eat animals, often small ones such as insects, birds, frogs and other small mammals.

In Alaska it is illegal to whisper in someone’s ear while they’re moose hunting.

The bat is the only mammal that can fly.

The leg bones of a bat are so thin that no bat can walk.

Some male songbirds sing more than 2000 times each day.

The only mammals to undergo menopause are elephants, humpback whales and human females.

Blue-eyed lemurs are one of two (non-human) primates to have truly blue eyes.

A tarantula spider can survive for more than two years without food.

For every human in the world there are one million ants.

If you lift a kangaroo’s tail off the ground it can’t hop – they use their tails for balance.

If you keep a goldfish in a dark room, it will become pale!

Cows can sleep standing up, but they can only dream lying down.

The sentence “The quick brown fox jumps over a lazy dog.” uses every letter of the alphabet.

The average fox weighs 14 pounds.

The scientific name of the red fox is Vulpes vulpes.

Alligators can live up to 100 years.

A single elephant tooth can weigh as much as 9 pounds.

The turkey is one of the most famous birds in North America.

A housefly hums in the key of F.

During World War II, Americans tried to train bats to drop bombs.

Canis lupus lupus is the scientific name for a grey wolf.

To escape the grip of a crocodile’s jaw, push your thumb into its eyeballs-it will let you go instantly.

It is much easier for dogs to learn spoken commands if they are given in conjunction with hand signals or gestures.

Even a small amount of alcohol placed on a scorpion will make it go crazy and sting itself to death!

Male rabbits are called “bucks,” females are “does.”

The flamingo can only eat when its head is upside down.

Animals generate 30 times more waste than humans which is 1.4 billion tons every year.

Ants never sleep. Also they don’t have lungs.

A group of owls is called a parliament.

Just one cow gives off enough harmful methane gas in a single day to fill around 400 litre bottles.

Apple and pear seeds contain arsenic, which may be deadly to dogs.

Cows have four stomachs.

An anteater is nearly 6 feet long, yet its mouth is only an inch wide.

The blue whale weighs as much as thirty elephants and is as long as three Greyhound buses.

A herd of sixty cows is capable of producing a ton of milk in less than a day.

A grasshopper can leap 20 times the length of its own body.

At birth, baby kangaroos are only about an inch long – no bigger than a large water bug or a queen bee.

The smell of a skunk can be detected by a human a mile away.

There is a butterfly in Africa with enough poison in its body to kill six cats!


Newly discovered properties about the

venom of a deadly and strikingly

beautiful snake - dubbed the "killer of

killers" - may lead to new pain treatments

for humans. A new international study of

the blue coral snake finds its unique

venom paralyzes its prey in a different

way to that of other paralyzing poisonous

snakes. Its usefulness to pain

management could lie in the way it acts

on a type of sodium channel, say the

researchers.

The team - including scientists from

Australia, China, Singapore, and the

United States - reports the findings in the

journal Toxins. The German philosopher

Friedrich Nietzsche once said, "That

which does not kill us, makes us

stronger."

Whether one agrees with Nietzsche or

not, it cannot be denied that his assertion

serves as a useful maxim for the medical

use of venom toxins. This natural source

of bioactive compounds has given rise to

drugs that relieve pain and treat a range

of ailments, including cancer, diabetes,

obesity, and heart failure.

The study of venoms shows that the toxic

proteins and amino acids they contain

known as peptides - act on cell receptors

and ion channels, controlling how cells

behave. The range of medical

applications is vast and continues to

grow. For example, a recently published

study suggests that tarantula venom

might be used to treat irritable bowel

syndrome, while another earlier one

proposed milking the venom of deadly

jellyfish could lead to new medicines.

However, it was only recently that this

vast and disparate knowledge was

brought under one roof, when a team

recently compiled

an open-source

library that

documents nearly

43,000 effects on

the human body

produced by the

application of venom toxins.

Venom delivers 'massive shock'

The motive for the new study stems from

a desire to better understand the

fascinating evolution of venoms. These

predatory and defensive weapons have

evolved over millions of years and today

are used by over 173,000 species in the

wild. The South-East Asian long-glanded

blue coral snake Calliophis bivirgatus is

unusual among snakes in that it preys on

other venomous snakes that move fast

and also present a significant danger to

itself - such as young king cobras.

This "killer of killers" - with its electric

blue stripes and neon red head and tail -

is one of the world's most beautiful

snakes, and yet, despite its notoriety, the

coral snake's venom has remained largely

unstudied, note the researchers.

Another striking feature is the blue coral

snake's venom glands. Possibly the

biggest venom glands of any poisonous

species found so far, they extend over a

quarter of the length of the snake's body.

When they investigated its properties,

the researchers found that the coral

snake's venom "produces spastic

paralysis, in contrast to the flaccid

paralysis typically produced by

neurotoxic snake venoms." The venom

delivers a massive shock to the prey's

nervous system, triggering full body

spasms by causing all nerves to fire at

once.

Venom turns off sodium channels

One of the senior and corresponding

authors, Bryan G. Fry, an associate

professor in

the School of

Biological

Sciences at

the

University of

Queensland

in Australia, says: "This style of

venomous predation is identical to that

of a cone snail, and not like any other

snake in the world."

The cone snail's venom induces rigid

paralysis in its prey. The caught fish's

muscles tense up in a spasm like that of

tetanus. "This keeps the fish from

escaping the immobile snail," Prof. Fry

explains. "Now it has been shown there is

a snake that kills the same way."

While the venom acts fast, it does not kill

immediately. Instead, it instantly

switches on all the nerves of the fast-

moving prey - which is also a predator -

rendering it frozen and immobile.

The venom does this "by preventing the

nerves from turning off their sodium

channels, keeping the nerve firing

continuously," says Prof. Fry.

The team concludes that the coral

snake's venom toxin demonstrates a

"remarkable case of functional

convergence between invertebrate and

vertebrate venom systems in response to

similar selection pressures." They note

that the discovery also "reinforces the

value of using evolution as a roadmap for

biodiscovery."

VETERINARY

AROUND THE GLOBE

Deadly snake's unique paralyzing venom may lead to new pain treatments


Source – The Guardian

he children in the villages around the Indian city of Nabha in Punjab state all know

what Horlicks is, although few have tasted it. The malted milk drink, manufactured by GlaxoSmithKline (GSK), is produced at the Horlicks plant in Nabha, which sources from around 1,500 dairy farmers in the surrounding area.

But after several years of severe drought in a region already heavily reliant on groundwater, water reserves are in decline and fodder for cows is becoming more expensive. This is making dairy production increasingly difficult in one of the highest milk-producing states in the country – itself the world’s largest national producer of dairy.

GSK is not the only big business facing drought-related problems in Punjab. Danone buys 50,000 – 80,000 litres of milk from 5,000 farmers in 100 villages in the state, and Nestlé sources more than 300m litres of milk from 100,000 farmers in three Indian states, including Punjab. To ensure a steady supply of milk, these companies have set up long-term sustainability projects in Punjab’s villages. But, as water shortages worsen, can they protect dairy farmers from the potentially devastating effects of continuous droughts?

India’s ‘white revolution’ under threat

In 2012, Punjab’s chief minister Parkash Singh Badal called for a “white revolution”, encouraging the state’s farmers to take up dairy since, he said, most were too reliant on wheat-paddy rotation crops with slim profit margins.

This revolution requires water. One cow consumes approximately 150 litres of drinking water a day. Water is also needed to produce fodder for cows. Fertile lands and good infrastructure in the state such as dams and irrigation systems have helped stave off the kind of acute water shortages witnessed in other parts of India over the last few decades. But the severity of the latest El Niño weather cycle has led to unprecedented temperatures, causing rivers, lakes and dams to dry up in many parts of northern India. In Punjab, low rainfall has decreased crop yields and put a huge strain on the state’s diminishing groundwater resources.

“In the winter, cows can graze in the fields. But in the summer when there’s no rain we have to buy fodder,” says Harpreet Singh, a dairy farmer from the village of Issi who supplies milk to Horlicks. “It’s a big problem for us ... The cost of fodder keeps increasing but the price of milk stays fixed, so the entire business is in decline.” Harpreet Singh makes approximately 50,000 rupees (£570) profit a month in the winter, but says his losses in the summer leave him

without savings. Horlicks’ farmers aren’t the only ones facing this crisis. On its website, Nestlé says: “Largely due to local over-exploitation by agriculture, industry and domestic use, the local water table is dropping by up to a metre a year and could affect the supply of milk in our Moga milk district [in Punjab].”

Industry support

To help farmers like Harpreet Singh cut down costs, GSK has set up education camps where farmers learn how to make their own silage from surplus grass, which can be used as cow feed in the dry season. Even though he’s feeling the pressure, Harpreet Singh says this is helping: “It’s a lot of effort, but in the summer it means we spend much less on buying fodder.”

GSK also produces a magazine offering dairy farmers advice on topics such as water reuse. The initiatives are an effort to keep the dairy business booming: “Our hope is that, through working together, we can help local farmers remain in business, assuring our supply of milk for Horlicks,” says a company spokesperson.

Danone, which makes Activia yoghurt, started sourcing milk from Punjab in 2012. Last year, the company set up Punjab 2020, an initiative which educates farmers in ways to improve soil quality by reducing fertiliser use so it retains more water, and maximise milk production in the context of drought.

T

VETERINARY

AROUND THE GLOBE

Dairy in distress: the milk revolution draining Punjab dry


About 7,000 farmers have already gone through the company’s Academilk training programme and it has invested €570,000 (£508,000) to expand the programmes to 60 more villages.

As part of Danone’s programme, the company provides communal chilling facilities, enabling those with even one or two cows to earn an income without having to invest in expensive coolers. “It is a win-win situation as it ensures a sustainable livelihood for the farmer while securing the milk supplies for Danone,” said a company spokesperson.

The groundwater dilemma

Vibha Dhawan, senior director at the Energy Resources Institute, says that while companies are helping provide short-term solutions to prevent the dairy industry’s collapse, the urgent problem of groundwater over-extraction still needs to be addressed.

Cost isn’t the only problem for those relying on groundwater. “As groundwater levels go down,” explains Dhawan, “the risk of arsenic or lead poisoning in the water increases because heavy metals settle lower down. If farmers keep extracting as they have ... the quality of the water, which ultimately goes into our milk, will also reduce.”

While the companies have not yet found solutions to this, Nestlé has started funding research with the International Water Management Institute to understand the causes of groundwater depletion in the area surrounding its factory, in the Moga district. The research – which the company runs alongside wider farmer support programmes, such as cattle feeding, breeding, and veterinary support – includes a six-month pilot project investigating the company’s water footprint from milk.

Dhawan believes the Punjab government is partly to blame for the groundwater crisis as it subsidises electricity for water extraction. Big companies and the government need to start investing in water-wise technology, she says, such as sub-soil irrigation, where pipes supply the soil at root level so less water is lost through evaporation, or precision agriculture methods, where farms are monitored by computer so exact amounts of inputs can be applied.

“These are already technologies that exist, but they need to be made available to farmers,” says Dhawan.

Mysuru district administration urged to set up fodder banks

The Animal Husbandry Department has made an appeal to the district administration to set up fodder banks in 16 dry places in the district to tackle the problem of fodder shortage.

P.M. Prasad Murthy, Deputy Director, Animal Husbandry Department, told The Hindu that tonnes of fodder will be stored in these fodder banks and will be sold to farmers at half of the original price. Except a few villages — which have irrigation facilities — most of the villages are experiencing fodder shortage and farmers are finding it difficult to feed fodder to their animals, he said.

There are over 5,43,000 head of cattle, including buffaloes, in the district, he said, adding the number is about 10 lakh if other animals, including goats and sheep, are included. Four fodder banks each in Mysuru and Nanjangud taluks, two each in Hunsuru, H.D. Kote and Piriyapatna taluks and one each in T. Narasipur and K.R. Nagar taluks have been sought. The district is witnessing fodder shortage as all the seven taluks are reeling under drought and crops have been damaged in most parts of the district, Mr. Prasad Murthy said, adding that the fodder stock available with a few farmers may last for a few more weeks.


Identify Disease Condition

You are presented with a 5-year-old Holstein cow 3 days after assisted delivery of live twins. The cow has a daily milk yield of only 12 L. On clinical examination the cow is dull and depressed, inappetant, with a poor milk yield. The cow is febrile with a rectal temperature of 40.2°C (104.4°F). The cow has diarrhoea but there is no evidence of blood or mucosal casts in the faeces. The mucous membranes are congested. The vulva is slightly swollen with evidence of a red–brown fluid discharge. At least one placenta is retained.

i. What is your diagnosis?

ii. What treatments would you consider?

iii. What are the possible consequences?

iv. What factors are believed to contribute to retained placenta?

A pigeon loft owner reported

multiple problems in his loft of

racing pigeons, including birds

with swollen hock or wing joints,

increased numbers of dead-in-

shells and clear eggs, mortality in

young squabs and diarrhoea with

marked weight loss. An occasional

bird exhibited nervous signs such

as twisting of the neck and difficulty feeding.

i. What is the most likely diagnosis?

ii. How would you attempt to treat and control this disease?

iii. How would you differentiate this disease clinically from other

causes of nervous disease in pigeons?

- Answers will be published in next issue


Inject correctly


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