Getting a Cat to Stop Spraying Inside

Cat Spray No More

Cat Spraying no more is a product that will guide the users on the way to prevent the various mess made by their cats. It is true that a cat that pees in the house can make their home smell like a litter box; it can be upsetting and stressful for the users and can become incredibly expensive if the users are forced to continually clean carpets and floors, or replace furniture. However, Cat Spraying No More is one that will help in the reduction of these problems because it will point the users towards the right things to do and what not to do as regards their cats. This product will stop their cat peeing and spraying outside the litter box for good. This professionally created and proven system will work whether their cat has just started peeing where they should not or if they've been doing it for years. This product is a cheap one that can be learnt by anyone. It comes with certain bonuses that will change the way the users see things as regards cat. They are Cat Training Bible, 101 Recipes for a Healthy Cat, The Cat Care Blueprint, Pet Medical Recorder Software. Read more here...

Cat Spray No More Summary


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Author: Sarah Richards
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My Cat Spray No More Review

Highly Recommended

The writer presents a well detailed summery of the major headings. As a professional in this field, I must say that the points shared in this manual are precise.

When compared to other ebooks and paper publications I have read, I consider this to be the bible for this topic. Get this and you will never regret the decision.

Cat Spray Stop

Susan Westinghouse is the creator of the cat spray stop program. She is an avid veterinarian and cat expert with lots of years of experience. She claims that the guide offers a broad outline and precise approaches targeted at preventing your cat from spraying, despite your cat's stubborn or persistent personality. According to her, it contains the exclusive TTS Taste, Touch, Smell method for pinning the issue, therefore the guide works to stop the cat from spraying and discourages him to ever repeat the bad behavior in the future. It is an e-book that comes with two bonuses attached to it. The first bonus is a nutritional program that will help your cat lose unnecessary weight, while the second bonus is an essential oil recipe for cats that will help to reduce their stress level. This program is suitable for any owner who lives with a cat that has bad litter box habits and often sprays. Susane Westinghouse's guide is characterized by ease of use and it contains a ton of helpful tips that make the process a lot easier both for you and your furry companion. The program is spread across six chapters that take you through a comprehensive tour in how you can solve this annoying problem now, while also learning how to keep it from coming back to haunt you later on in the future. Read more here...

Cat Spray Stop Summary

Contents: Ebook
Author: Susan Westinghouse
Price: $37.00

Background Occupational Lower Back Disorders

As many as 85 of adults experience lower back pain that interferes with their work or recreational activity and up to 25 of the people between the ages of 30 to 50 years report low back symptoms when surveyed 1 . Of all lower back patients, 90 recover within six weeks irrespective of the type of treatment received 2 . The remaining 10 who continue to have problems after three months or longer account for 80 of disability costs 1 . Webster and Snook 3 estimated that lower back pain in 1989 incurred at least 11.4 billion in direct workers' compensation costs. Frymoyer and Cats-Baril 4 estimated that direct medical costs of back pain in the U.S. for 1990 exceeded 24 billion, and when indirect costs predominately associated with workers' compensation claims were added, the total cost was estimated to range from 50 billion to 100 billion. One U.S. workers' compensation insurance company incurred costs for lower back pain of about 1 billion per year, whereas the total cost for carpal tunnel...

Potential Duration of Delivery

The duration of oral controlled release systems is often dictated by the intended species. In general, oral VCRS are not useful in cats, dogs, and pigs with gastrointestinal transit times of approximately 3-8 h,4,5 but are feasible for cattle, sheep, and horses with transit times approaching 3 days.6-9 In addition, effective oral VCRS dosing in ruminants can be achieved using bolus devices that remain trapped in the rumen for several months duration.10 However, oral administration of antimicrobial agents to ruminants may have unacceptable gastrointestinal effects resulting from alterations in the composition of gut microflora.

Twodimensional descriptors

More recent descriptors include the Chemically Advanced Template Search (CATS) descriptors, Similog keys, and Scitegic circular fingerprints. The CATS descriptors53 are based on counts of atom pairs up to 10 bonds distant, with the atoms classified as lipophilic, positive, negative, donor, and acceptor. The 15 possible pairs of atoms and 10 distances give rise to a vector of length 150. The Similog keys54 represent triplets of atoms. Each atom is represented by the presence or absence of the following four properties donor, acceptor, bulkiness, and electropositivity (known as the DABE code). A Similog key for a molecule consists of a list of triplets of atoms, with each atom described by its DABE code, the topological distances between the atoms mapped to four intervals, and the frequency of occurrence of the triplet.

Histamine receptor antagonists

Of the four members of the histamine receptor superfamily, the H3 is predominately expressed in the brain, localizing to cerebral cortex, amygdala, hippocampus, striatum, thalamus, and hypothalamus. H3 receptors are localized presynaptically on histaminergic nerve terminals and act as inhibitory autoreceptors thus, when activated by histamine, histamine release and biosynthesis are blocked.38 Of relevance to AD, H3 receptors expressed on nonhistaminergic nerve terminals can modulate the release of ACh, DA, g-amino-butyric acid (GABA), glutamate, and serotonin. Thus, H3-receptor antagonists or inverse agonists, by blocking the inhibitory effects of histamine, will facilitate the release of multiple neurotransmitters, reminiscent of the effects of nAChR activation. H3-receptor antagonists enhance vigilance, promoting wakefulness in rats, mice, and cats, and improve cognitive function in a variety of preclinical models. H3-receptor inverse agonists are thus being targeted as therapeutics...

Unraveling the Role of Serotonin 5hydroxytryptamine 5HT and Norepinephrine in Control of Lower Urinary Tract Function

In support of de Groat's iontophoretic studies and the electrical stimulation studies, we found that a 5HT receptor agonist, 5-methoxy-dimethyltryptamine (5-MeODMT), inhibited bladder activity and enhanced sympathetic and somatic outflow to the urethra in cats.9 Importantly, the doses that inhibited bladder activity were lower than those that excited the sympathetic and somatic outflow to the urethra, which was ascribed to differential affinity of 5-MeODMT for 5HT1 and 5HT2 receptors. (The plethora of 5HT receptor subtypes was just beginning to be realized when these studies were initiated and selective agonists and antagonists were scarce.) However, the picture became complicated when studies by Lecci in Maggi's group10 showed that 8-OH-DPAT, a 5HT1A receptor agonist, enhanced bladder activity in rats. Studies in my laboratory with 8-OH-DPAT confirmed Lecci's results in rats but showed completely opposite effect in cats, i.e., an inhibition of bladder activity, in support of my...

Discovery of Duloxetines Preclinical Effects on the Lower Urinary Tract

In the first series of experiments testing duloxetine's effects on lower urinary tract function,27 I chose to use the cat as the experimental species because most of the preceding experiments with 5HT and norepinephrine had been conducted in cat and thus provided benchmarks upon which to interpret the effects of duloxetine. I also chose to use a model of bladder irritation, i.e., infusion of dilute acetic acid into the bladder, to induce 'overactive bladder' because the importance of nociceptive (i.e., C fiber primary afferent neurons) stimuli in the etiology of overactive bladder was just beginning to emerge. As luck would have it, both of these choices were critical because subsequent studies showed that duloxetine has very little effects on normal (i.e., saline infused - unirritated) bladder activity, presumably because 5HT and or norepinephrine have greater effects on 'irritative,' C fiber-mediated bladder activity than normal bladder primary afferent fibers. Subsequent studies...

Design considerations Substrate thickness Substrate thickness is a feature that is of importance when it comes to insertion into tough tissue or into deep structures. The standard Michigan probe process is capable of producing probes 5 to 15 m in thickness based on the time and temperature of the boron diffusion and hence the depth of the etch-stop. Probes 15 im thick and 5 mm long and tapered from 15 to 120 im in width are capable of penetrating the pia with minimal bending in most preparations. If the device is much longer than this, however, the buckling force is lower. If a very long shank is absolutely required by the application, a stronger, stiffer device can be achieved by forming a box-beam substrate. This type of device uses the same fabrication process as the Michigan chemical delivery probe80 to form an open channel within the silicon substrate (Figure 7.7). This channel results in a box-beam structure that is inherently stiffer and stronger than a normal beam because the second moment...

Library Design Based On Special Data Mining Algorithms

A fine illustration of a SOM-based virtual screening procedure that was used to construct focused combinatorial libraries and to identify products with optimized biological properties against the human A2A purinergic receptor has been reported 50 . A SOM was developed with a 153-member combinatorial library of general structure 1 (Fig. 15.4). This set was tested to establish a preliminary structure-activity relationship. For SAR modeling by self-organizing networks, all molecules were represented by the CATS phar-macophore descriptor, which is based on a topological correlation of generalized atom types. The secondary combinatorial library design was performed by projecting virtually assembled new molecules onto the SOM. As a result, a small, focused library of 17 selected combinatorial products was synthesized and tested. On average, this small library displayed a 3-fold lower binding constant and 3.5-fold higher selectivity than the initial library. The most selective compound of...

TType Selective Ca2 Channel

The T-type selective channel blocker lead structure mibefradil (IC50 1.2 M) served as a template for virtual screening of the Hoffmann-La Roche in-house compound collection. Several filters were applied, and the similarity of the candidates to the lead structure was compared by the CATS descriptor 89 . Because only pharmacophoric features and their topological distances describe the molecules, the CATS descriptor enables a scaffold hopping that is, molecules with different scaffolds but comparable biological properties result from this approach. The 12 highest-ranking molecules were biologically tested nine of them showed T-channel blocking activities in the same range as the lead structure mibefradil. Whereas one highly active compound was the known neuroleptic clopimozide 68 (IC50 < 1 M Fig. 16.9) 89 , several other active hits, for example, compounds 69 (IC50 2.4 M Fig. 16.9) 63,141 and 70 (IC50 0.8 M Fig. 16.9) 141 , are new chemotypes. Despite the topological pharmacophore...

Sperm Chromatin Structure Assay for Fertility Assessment

SCSA data on thousands of semen samples from humans (Evenson 1997, 1999a Evenson et al., 1991, 1999 Fossa et al., 1997 Larson et al., 1999, 2000 Grajewski et al., 2000), bulls (Ballachey et al., 1987, 1988 Evenson, 1999b), stallions (Evenson et al., 2000b), boars (Evenson et al., 1994), and exotic cats (unpublished) show the clinical value of this assay for human animal fertility assessment.

From Animal Pharmacology to a Human Therapeutic

Following the discovery of the stimulant effects of adrafinil in rodents, it was essential to select a viable therapeutic indication consistent with the effects observed. At that time, Lafon had a research and development agreement with a large pharmaceutical company that wanted to focus clinical studies and indications in 'psychogeriatrics.' That led to a new drug application being filed only in France with an approval for 'vigilance and mood disorders in the elderly.' At the same time Louis Lafon had the opportunity to meet Professor Michel Jouvet, the world-renowned sleep expert from the University of Lyons, France, who was mainly interested in the stimulant properties of the compound. He anticipated that these would be linked to awakening effects. To demonstrate that idea, he initially used a cat model of sleep-wake and in preliminary studies confirmed his hypothesis, that modafinil could produce a quiet wakefulness in cats, an effect that was subsequently confirmed in monkeys.15...

In Search of a Mechanisms of Action

As soon as the original profile of adrafinil was described, a number of research teams, among them some with existing collaborations with Laboratoire L. Lafon, used different approaches in attempts to elucidate the mechanism(s) of action of adrafinil and modafinil, in order to differentiate them from amphetamine and methylphenidate. Using classical pharmacological probes known to interact preferentially (but probably not specifically) with neurotransmitter systems and receptors, it was found that centrally but not peripherally acting -adrenoceptor antagonists reduced the stimulant and wake-promoting effects of both adrafinil and modafinil locomotor activity in mice,5'6'24 nocturnal activity in monkeys,12,13 electroencephalogram sleep-wake in cats,10 and convulsions in quaking mice.25,26 Moreover, while the motor stimulant and wake-promoting effects of amphetamine and methylphenidate were blocked by the dopamine receptor antagonists, haloperidol or sulpiride, and by a-methyl tyrosine...

Anisogamy and the Bateman Paradigm

The conviction that intrasexual selection will weigh heavily upon males while scarcely affecting females was explicitly stated by Bateman, but also appears in implicit form in the writings of contemporary sociobiologists (Daly & Margo Wilson, 1983, Chapter 5 Wilson, 1978, p. 125). It is undeniable that males have the capacity to inseminate multiple females while females (except in species such as those squirrels, fish, insects, and cats, where several fathers can sire a single brood) are inseminated at most once each breeding period. But a difficulty arises when the occasionally true assumption that females are not competing among themselves to get fertilized is then interpreted to mean that there will be reduced within-sex competition among females generally (e.g., Freedman, 1979, p. 33).

Discharge And Home Healthcare Guidelines

Teach the patient and significant others about the course of the disease, the treatment options, and how to recognize complications. Explain that the patient or parents need to notify the physician if any of the following occur fever, chills, cough, sore throat, increased bleeding or bruising, new onset of bone or abdominal pain. Discuss the patient's home environment to limit the risk of exposure to infections. Encourage the patient to avoid close contact with family pets because dogs, cats, and birds carry infections. Animal licks, bites, and scratches are sources of infection. The patient should not clean birdcages, litter boxes, or fish tanks. Additional sources of bacteria in the home include water in humidifiers, standing water in flower vases, and water in fish tanks. Encourage the patient to have air filters in furnaces and air conditioners changed weekly. Explain that raw fruits, vegetables, and uncooked meat carry bacteria and should be avoided. If the patient becomes...

From Adrafinil to Modafinil

Because of the similar effects of adrafinil and modafinil and the available preclinical experimental data obtained with adrafinil (particularly in toxicological studies), the development of modafinil moved forward, mainly focused on putative therapeutic applications, a search for the mechanism of action, and a differentiation from amphetamine- and nonamphetamine-like stimulants. The initial publication of the unique behavioral profile of modafinil6 aroused considerable interest from several research groups, resulting in many subsequent animal studies that confirmed, in a variety of species - mice,7 rats,8'9 cats,10 narcoleptic dogs,11 monkeys,12'13 and even fruitfly14 - the stimulant and awakening effects of the compound. Simultaneously, every effort was made to generate additional data to advance knowledge related to modafinil to the same level as that which was known regarding adrafinil, in order to provide a choice between the two compounds for further development. At the same...

Optic nerve neuroprosthetic approach

Figure 11.7 Potential neural interface, the USEA, for access to the optic nerve. The array of 100 electrodes, shown to the left, has been successfully used in peripheral nerve of cats. As each row of 10 electrodes has a unique length, ranging from 0.5 to 1.5 mm, each row of electrodes accesses a unique depth in the nerve, as shown in the center panel. Thus, this structure could potentially access 100 unique axonal fibers within a nerve, as illustrated in the right panel. The distance between rows (and columns) of electrodes is 400 im. Figure 11.7 Potential neural interface, the USEA, for access to the optic nerve. The array of 100 electrodes, shown to the left, has been successfully used in peripheral nerve of cats. As each row of 10 electrodes has a unique length, ranging from 0.5 to 1.5 mm, each row of electrodes accesses a unique depth in the nerve, as shown in the center panel. Thus, this structure could potentially access 100 unique axonal fibers within a nerve, as illustrated in...

The Females Who Forgot to Be

It has been known for years (among some circles) that female birds were less than chaste, especially since 1975 when Bray, Kennelly, and Guarino demonstrated that when the ''master'' of the blackbird harem was vasectomized, his females nevertheless conceived (see also Lumpkin, 1983). Evelyn Shaw and Joan Darling (1985) review some of this literature on ''promiscuous'' females, particularly for marine organisms. Among shiner perch, for example, a female who is not currently producing eggs will nevertheless court and mate with numbers of males, collecting from each male sperm that are then stored in the female's ovaries till seasonal conditions promote ovulation. Female cats, including leopards, lions, and pumas are notorious for their frequency of matings. A lioness may mate 100 times a day with multiple partners over a 6-7-day period each time she is in estrus (Eaton, 1976). Best known of all, perhaps, are such primate examples as savanna baboons, where females initiate multiple brief...

Implications of Confabulation Theory

A large-scale human brain modeling project of this sort will surely require a widely knowledgeable and exceptionally well educated team of hundreds of mathematical neurobiologists and computer scientists operating as willing and compliant subordinates under the hierarchical command of a master genius. The usual herd of cats sort of scientific research program would probably not work effectively in this instance. I personally know at least five people who could each probably successfully lead such an effort. Such an integrated brain modeling project is, in my opinion, one of the most important tasks that the human species should now carry out. It will be expensive (probably exceeding 200,000,000 per year for a decade along with another 400,000,000 for a proper building to house the project and the budget for the required equipment). A single, open, international project of this type would seem ideal. However, given the potential economic and national security implications, multiple...

Axonal Arbors Are Refined Or Eliminated

The wholesale withdrawal of axons provides a wonderful example of developmental refinement, but unfortunately for the anatomist this is not the norm. Changes in terminal arbor morphology are usually quite subtle. An axon tends to innervate the correct target region (Chapter 6), extend a bit beyond the correct topographic position, and then pull back to the adult boundary. Perhaps the best characterized examples of axon terminal elimination come from the developing visual pathway. In cats and primates, retinal ganglion cells from each eye project to separate layers in the lateral geniculate nucleus (LGN). The LGN neurons then project to Layer IV of the visual cortex, forming segregated eye-specific termination zones, called ocular dominance columns or stripes (Figure 9.5A).

Sensory Coding Properties Reflect Synapse Rearrangement

A similar finding is obtained in cats that were deafened by damaging the inner hair cells, and then stimulated electrically within the cochlea. This is a highly relevant experimental model because children with profound hearing loss are now routinely implanted with cochlear prostheses, and they hear the acoustic world via electrical stimulation of their cochlea

Spontaneous Activity And Afferent Segregation

We previously learned that stripes in Layer IV formed in binocularly deprived cats (Figure 9.10). To test whether spontaneous retinal activity might be responsible for the segregation of thalamic afferents in the cortex, retinal activity was completely eliminated by injecting both eyes with TTX from about 2-6 weeks postnatal (Figure 9.20). In TTX-reared cats, the LGN afferents fail to segregate into stripes in Layer IV of the cortex (Stryker and Harris, 1986). Similarly, suppression of spontaneous retinal activity prevents the elimination of small retinal afferent sidebranches in the inappropriate layer of LGN. However, the TTX injections were made after the thalamic afferents had begun to segregate in the cortex, and it is possible that this manipulation leads normally refined afferent projections to sprout, once again, into an inappropriate target region (Chapman 2000).

Background Information

Toxoplasma gondii exists in three forms the tachyzoite, which is the asexual invasive form the tissue cyst (containing bradyzoites), which persists in tissues of infected hosts during the chronic phase of the infection and the oocyst (containing sporozoites), which is produced during the sexual cycle in the intestine of cats (the definitive host). The extraintestinal asexual cycle is present in all incidental hosts and in cats. After ingestion of tissue cysts or oocysts, either bradyzoites or sporozoites, respectively, are released into the intestinal lumen, where they invade surrounding cells, become tachyzoites, and disseminate throughout the body via the blood and lymphatics. The tachyzoite requires an intracellular habitat for survival and can infect all mammalian cell types. Tachyzoites are found in tissues during the acute stage of the infection or during reactivation of the chronic (latent) infection. Approximately 10 to 14 days after infection, tachyzoites disappear and cysts...

Many Forms Of Plasticity Have A Time Limit

Synaptic activity begins to exert an influence soon after synaptogenesis, but how long does this process continue If we embrace learning and memory in our definition, then it lasts for our entire lifetime (Box Remaining Flexible). However, there are certain significant changes in nervous system structure and function that only occur during a limited period of development (Berardi et al., 2000 Hensch, 2004). A common example is language acquisition, which is accomplished most easily before age 10 and becomes a grueling task for most of us if attempted as adults (see Chapter 10). At least some forms of neuronal plasticity only last for a limited period during developmental, often called a critical period. The influence of visual experience on ocular dominance has been explored in older animals to determine whether cortical neuron function is always dependent on vision (Hubel and Wiesel, 1970). Ocular dominance is most susceptible to monocular deprivation after several weeks of sight....

Infecting Ferrets With H Mustelae

Ferrets are much larger than rodents and serve as an example of both a larger Helicobacter animal model and a naturally occurring model using an indigenous organism. Unlike cats, another relatively large H. pylori animal model, which must be anesthetized for almost any experimental manipulation, ferrets are much easier to handle and do not require anesthesia for oral immunization or inoculation. The biggest drawback to the ferret as an animal model is the paucity of immunologic reagents available.

Organisms In External Environment

Originally described by Tyzzer (1910, 1912), Cryptosporidium has emerged as an important pathogen of human beings in the last 25 years. Although more than 20 'species' of this coccidian parasite have been described on the basis of the animal hosts from which they were isolated, host specificity as a criterion for spe-ciation appears to be ill founded as some 'species' lack such specificity. Currently, there are ten 'valid' species C. parvum, C. andersoni and C. muris which infect mammals C. baileyi and C. meleagridis which infect birds C. serpentis and C. nasorum which infect reptiles and fish respectively C. wrairi has been described in guinea pigs C. felis in cats and C. saurophilum in lizards. Cryptosporidium felis has also been identified as a cause of infection in humans, in a small number of cases. The discovery of DNA sequence-based differences within the riboso-mal RNA (rRNA) gene repeat unit between individual isolates within a 'valid' species means that the taxonomy of the...

Classification Methods

While QSAR methods aim to predict absolute compound activity, classification methods attempt to bin compounds by their potential hERG inhibition. The earliest example of a hERG-based classification was reported by Roche and coworkers.57 A total of 244 compounds representing the extremes of the data set (< 1 and> 10mM for actives and inactives, respectively) were modeled with a variety of techniques such as substructure analysis, self-organizing maps, partial least squares, and supervised neural networks. The descriptors chosen included pKa, Ghose-Crippen,58 TSAR,59 CATS,60 Volsurf,61 and Dragon62 descriptors. The most accurate classification was based on an artificial neural network. In the validation set containing 95 compounds (57 in-house and 38 literature IC50 values) 93 of inactives and 71 of actives were predicted correctly.

Neural and Cortical Plasticity Reorganization

Animal research in the area of cortical plasticity and reorganization as regards the auditory system is intriguing and bears directly on the last controversy considered in this chapter. The phenomenon of failure to develop perceptual ability, due to early sensory deprivation, has been well recognized for many years, beginning with studies of kittens that were kept in darkness, and including newborn mice that were denied auditory input.19 The outcomes in those experiments showed lack of development of visual cortex and visual perceptual abilities in the first case and noticeable changes in structure of various nuclei in the auditory pathways of the brainstem and midbrain in the latter instance. More recently, reports on declines in speech perception abilities in the unaided ear of adults who are long-term monaural hearing aid users bring this question to the forefront again. Finally, research on apparent cortical reorganization in newborn cats whose auditory cortex is examined several...

Infection Of The Skin

Dermatophyte infection (ringworm) is restricted to invasion of the stratum corneum, nails, and hair. The dermatophytes, Trichophyton, Epidermophyton, and Microsporum species may infect humans. Microsporum species are usually acquired from infected cats or dogs (M. canis) and are a frequent cause of tinea capitis (ringworm affecting the head) in children. Infections from farm or other animals tend to cause more vigorous inflammation than those from other sources. The infection may be diagnosed from microscopy of skin, nail, or hair treated with potassium hydroxide. Alternatively, the fungus may be cultured.

Obstructive sleep apnea

Neurotransmitters Reticular Formation

There are many neurotransmitters present in the motor nuclei of upper airway dilator motor neurons in the brainstem, and more centrally in the central nervous system (CNS), which are implicated in the neural control of upper airway patency 19, 20 . Glycine and 7-aminobutyric acid contribute inhibitory influences on upper airway motor neuronal activity 21 . Other neurotransmitters such as acetylcholine, glutamate, noradrenaline, thyrotropin-releasing hormone, substance P, vasopressin, oxytocin and orexin also have roles, but the pre-eminent excitatory neurotransmitter is serotonin (5-hydroxytryptamine, 5-HT) 22 . The relative importance and interplay between these neurotransmitters has been studied in vitro in reduced motor neuron preparations, and in vivo in healthy animals including cats, rats and a natural animal model of sleep-disordered breathing, the English bulldog. It is likely that there will be some differences between the results of these studies and the interplay of...

Studies of the Mechanism of Action of Gabapentin and Pregabalin

The original animal pharmacology studies of gabapentin from Goedecke (1981-1984 W Reimann, G. Bartoszyk, and others, unpublished data) included studies of anticonvulsant action in mice, rats, and monkeys and antispasticity effects in animal models with mice, rats, and anesthetized cats. Early mechanism of action work centered on electrophysiological changes in spinal reflexes (W Steinbrecher, 1982, unpublished data) and reduced monoamine neurotransmitter release from brain tissue slices in vitro (W Reimann, E. Schlicker). Also in 1984, a group of pharmacologists at Parke-Davis (P. Boxer, R. Anderson et al., Ann Arbor, MI, unpublished data) studied gabapentin in several preclinical models of spasticity in mice. Gabapentin reduced muscle rigidity and increased locomotor agility (apparently by reducing spinal polysynaptic reflexes) at dosages of 10-100mgkg-1 IP. The results with gabapentin compared favorably with other experimental treatments for spasticity (e.g., baclofen, diazepam)....

Correlated Chronometric and Psychometric Variables

(1) Any performance measurable as RT to an elementary task is necessarily much too simple to reflect the marvelously subtle, complex, and multifaceted qualities of the human intellect. A still pervasive legacy from philosophy to psychology is the now largely implicit mind-body dualism, which resists reductionist physical explanations of specifically human psychological phenomena. Any kind of RT was commonly viewed as a merely physical motor reaction rather than as an attribute of mind. Disbelievers in the possibility of an RT-IQ connection pointed out that many lower animals, for instance frogs, lizards, and cats, have much faster RTs than do humans (which in fact is true). And when confronted with good evidence of an RT-IQ correlation, they dismiss it as evidence for the triviality of whatever is measured by the IQ. These obstacles to research on RT are supported by belief systems, not by empirical inquiry.


This chapter will provide an overview of biopharmaceutical and pharmacokinetic principles that are essential in meeting the challenges facing innovative producers of veterinary controlled release products. In this chapter we focus on two major veterinary markets (1) livestock, including cattle, swine, sheep, and poultry and (2) companion animals, including cats, dogs and horses. The same general principles which are applied to pharmaceuticals for these major markets can be applied to pharmaceuticals for other markets, such as aquaculture, however, it should be noted that additional requirements or restrictions may need to be considered. We also have restricted this discussion to pharmaceutical agents and have excluded discussing biological agents such as vaccines.

Species Differences

During its evolution, every animal species was under an individual selection pressure with regard to drug metabolism, in major part dictated by its preferred diet. Thus, some major species differences in drug metabolism68,69 may tentatively be rationalized by species-specific requirements. Cats are exclusively carnivores. They almost completely lack the ability to glucuronidate xenobiotics, presumably because they do not have a need to render the easily glucuronidatable plant flavonoids or alkaloids excretable. For less obvious reasons, pigs are slow in drug sulfation and dogs are poor acetylators. The rat has extremely low levels of sEH in the liver.

Spinal Cord Injury

Interest in the LP hypothesis of secondary SCI evolved during parallel investigations of the effects of high-dose MP (15-90 mg kg 1 i.v.) on spinal cord electrophysiology in the context of improving impulse conduction and recovery of function in the injured spinal cord.39 A similar high dose of MP, which enhanced spinal neuronal excitability and impulse transmission, was tested for its ability to inhibit posttraumatic spinal cord LP. In an initial study in cats, an i.v. bolus of MP inhibited posttraumatic LP in spinal cord tissue, but the doses required were much higher (30mgkg_ 1) than those previously hypothesized, or those empirically employed in the clinical treatment of acute CNS injury or tested in the NASCIS trial. Additional studies in cat SCI models showed that at a dose of 30 mgkg 1 MP not only prevented LP but, in parallel, inhibited posttraumatic spinal cord ischemia, supported aerobic energy metabolism (i.e., reduced lactate and improved ATP and energy charge), improved...

Axon Regeneration

Lesion in neonatal hamsters or cats grow around the lesion site and are not able to penetrate the injury site (Bregman and Goldberger, 1983). Thus, there is thought to be something inhibitory at the lesion site. The importance of extracellular cues in vivo is clearly illustrated by the ability of peripheral nerve grafts to support central axonal regrowth (Richardson et al., 1980 David and Aguayo, 1981 Aguayo et al., 1990). In a set of classic studies, it was shown that while transected central axons were unable to grow within the CNS, they could grow for many centimeters through a sheath of nonneuronal cells that ordinarily provide insulation to motor axons in the periphery (Figure 5.38). Indeed, while embryonic and peripheral

VLA4 a4b 1 Antigen

Virtual screening comprises several computational techniques that have already shown their efficiency in delivering interesting lead structures. In the most effective application, cascades of different steps serve to reduce very rapidly the number of potential candidates from hundreds of thousands or even millions of structures to a manageable size, for example, by first applying simple filters (molecular weight, polar surface area, number of rotatable bonds, Lipinski rule of five, lead-likeness rules, drug-likeness neural nets), followed by pharmacophore generation and pharmacophore searches. The number of potential candidates can be reduced by a filter that checks the presence of all necessary pharmacophoric features. The generation of a phar-macophore hypothesis can be ligand based or may be derived from the protein 3D structure (if available) by a hot spot analysis (programs GRID 11, 156 , LUDI 35 , DrugScore 49, 157, 158 ). Ligand-based pharmacophore generation is most often...

Animal experiments

Both the Utah and the Michigan electrode arrays have been used in scores of electrophysiological experiments in a variety of sites in the nervous system in rats, turtles, cats, monkeys, guinea pigs, and ferrets. They have been used in both stimulation and recording applications in both acute and chronic preparations. Histological studies indicate that there is usually a little localized bleeding associated with their implantation, but this usually resolves itself quickly, and single- and or multi-unit recordings can be made within an hour or two of implantation. The fact that single-unit recordings can be made with these complex devices provides the best evidence that the neurons near the electrode tips have not been significantly damaged by the insertion process. The fact that recordings can be made on a chronic basis indicates that the materials used in their manufacture are biocompatible. The efficacy of the Utah Electrode Array as a means to stimulate neural tissues has been...


The benzodiazepines were recognized in animal experiments in the 1950s for their ability to produce taming without apparent sedation. Cats, which are extremely sensitive to even small electrical shocks, were obviously sedated when given enough alcohol or barbiturates to prevent anxious avoidance behavior of impending shocks. In contrast, when given benzodiazepines, the cats appeared normal in all of their behavior, except that they did not show the exaggerated anticipatory sensitivity to mild electrical shocks that they showed prior to treatment with benzodiazepines.


Selection of an appropriate Helicobacter animal model requires care and an understanding of the strengths and weaknesses of the various available models (Fox and Lee, 1997 Eaton, 1999). Ferret infection by H. mustelae occurs naturally and the disease produced is a reasonable mimic for human disease (Fox et al., 1990). Unfortunately the catalogue of immu-nologic reagents available for the ferret is extremely limited. A goat anti-ferret immuno-globulin reagent is available commercially (Kirkegaard & Perry see Suppliers Appendix), but reagents to distinguish ferret immunoglobulin isotypes have not been made commercially available. The authors are unaware of any antibodies with specificity to ferret T cells, but reagents prepared against mink immunoglobu-lins have been reported to cross-react with corresponding ferret portions. Other possible large-animal models include pigs, cats, and primates, which can all be infected with H. pylori. The disease process in these animals is often...


This apparent greater efficacy of pour-on formulations against external parasites is presumably the result of deposition of the active compound on, and in, the skin. The high lipophilicity of the macrocy-clic lactones is likely to result in the formation of depots of active ingredient in skin lipids and oil and fat secretions. This characteristic has been exploited in topical formulations of ivermectin that provide long-term residual control of blowfly and lice on sheep (Eagleson et al., 1993a, 1993b Thompson et al., 1994), and selamectin which controls fleas on dogs and cats for at least 1 month (Benchaoui et al., 2000). Even greatly exaggerated oral or injectable doses of macrocyclic lactones are considered unlikely to provide residual control of fleas (Zakson-Aiken et al., 2001). In sheep, topically applied ivermectin is thought to bind to skin lipids and secretions and may be passively distributed around the sheep's body in this medium following application to a discrete site...

Toxoplasma gondii

Cats and other felines are the reservoir for Toxoplasma gondii. Oocysts shed by these animals become infective 1-5 days later and may remain infective in water or soil for a year. Humans become infected upon ingesting the oocysts. For instance, children may become infected by playing in sand polluted with cat excreta. Infection may also occur through eating raw or undercooked meat containing the oocysts (cattle, birds, sheep, goats and pigs are intermediate hosts and may carry an infective stage of T. gondii) or food and water contaminated with feline faeces. To prevent toxoplasmosis, consumers and in particular pregnant women should be advised to avoid eating raw or undercooked meat, to wash vegetables carefully and wash hands after contact with cats. Irradiation of meat is also effective for killing T. gondii.

Spectrum and Potency

Interestingly, the spectrum of insects controlled by these products is remarkably similar (Shoop et al., 1995 McKellar and Benchaoui, 1996). The only macrocyclic lac-tones that have been specifically developed for primary insect control on animals are avermectins ivermectin for blowfly and lice control on sheep (Eagleson et al., 1993a, 1993b Rugg et al., 1993, 1995a, 1995b Thompson et al., 1994), and sela-mectin for flea control on cats and dogs (Benchaoui et al., 2000 McTier et al., 2000a, 2000b).

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