Studies on the epidemiology of trypanosomiasis in sheep and goats in Kenya

The epidemiology of trypanosomiasis in a tsetse-infested range area of Kenya was studied for 2 years in various breeds of sheep and goats. Observations, including infection rates, PCV, temperature and weight loss indicated that the exotic breeds were more susceptible to natural trypanosomal infection than the indigenous breeds and that the infection may be severely debilitating and in many cases fatal. Observations of tsetse numbers and rainfall in the grazing area during the first year showed that there was a significant correlation between tsetse numbers and rainfall of the previous month. The increase in tsetse numbers, which occurred one month after substantial rainfall, was followed by an increase in the prevalence of trypanosomiasis in the animals. However, during the second year when rainfall was low there was no correlation between tsetse numbers and rainfall. It was concluded that the seasonal incidence of trypanosomiasis and the possible trypanotolerance of the indigenous breeds are important factors to be considered when initiating a small stock improvement programme for trypanosomiasis-endemic areas.     

Potential interactions between non-steroidal anti-inflammatory drugs and other drugs

Objective: The objective of this review is to summarize what is known in human and veterinary patients regarding the potential interactions of non‐steroidal anti‐inflammatory drugs (NSAIDs) with clinically important drugs. Data sources: Relevant articles as identified through searches of Medline, 1985 to present. Human data synthesis: Hemodynamic drug interactions are most likely to cause clinically relevant problems in humans, in which NSAIDs blunt the response to anti‐hypertensive agents and diuretics in patients with cardiovascular disease, or cause renal decompensation in patients with hypovolemia. In addition, NSAIDs enhance the ulcerogenic effects of glucocorticoids or other recently administered NSAIDs, and can increase bleeding from anti‐coagulant drugs or from herbs with platelet inhibitory activities. Veterinary data synthesis: Although there are numerous studies examining the safety and efficacy of various NSAIDs in healthy or arthritic dogs, there are very few studies that address the safety of these agents in veterinary patients receiving medication for other acute or chronic conditions. Conclusions: Based upon what is known in humans, more studies are needed in veterinary patients to assess the safety of NSAIDs in those animals being treated with anti‐hypertensive, diuretic or anti‐coagulant drugs.     

The effect of flurbiprofen, a potent non-steroidal anti-inflammatory agent, upon Trypanosoma vivax infection in goats

Platelet aggregation leading to a decreased number of thrombocytes and reduced blood serotonin levels can be correlated with parasitaemia as has been observed in goats and cattle infected with T. vivax Y58. Flurbiprofen is a potent anti-inflammatory agent with antipyretic activity. In vitro , this agent inhibits platelet aggregation and blocks serotonin release. The results of the present study demonstrated that flurbiprofen inhibited the febrile reactions during the acute phase of T. vivax infection, but the drug did not prevent or reverse the associated drop in blood serotonin level during this period. Moreover, it was apparent that flurbiprofen had a deleterious effect on goats infected with T. vivax Y58. The infection in the untreated animals (sixteen out of seventeen goats) followed a rather mild and prolonged course with peaks of parasitaemia during the febrile episodes, whereas in flurbiprofen-treated goats (five animals), inoculated with the same number of trypanosomes, the parasitaemia was progressive and terminated in early death with disseminated intravascular coagulation at post mortem examination. These observations would seem to confirm the work of previous investigators, suggesting that anti-inflammatory agents have an aggravatory effect on the course of infection in animals inoculated with various strains of trypanosomes. Important differences exist, however, in the relationship between prostaglandin synthesis in the platelets of the goat and in those of other species.     

Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis

Strøm, H. & Krogsgaard Thomsen, M. Effects of non-steroidal anti-inflammatory drugs on canine neutrophil chemotaxis. J. vet. Pharmacol. Therap. 13, 186–191.
Non-steroidal anti-inflammatory drugs exhibit differences in their ability to suppress polymorphonuclear leucocyte (PMN) functions in different species. The present study investigated the in-vitro and ex-vivo effects of phenylbutazone and flunixin on leukotriene-B₄-directed migration of canine PMN. Furthermore, in-vitro comparison was made to indomethacin and the 5-lipoxygenase inhibitor, nordihydroguaiaretic acid (NDGA). In vitro , flunixin and NDGA were the most potent inhibitors, with IC ₅₀s of 13 and 7 μmol/l, respectively. Phenylbutazone had an IC ₅₀ of 42 μmol/l whereas indomethacin did not achieve 50% inhibition at concentrations less than 100 μmol/l. Ex vivo , flunixin almost completely abolished the LTB₄ response at 1h, and still possessed significant inhibitory activity 24 h after a dosage of 1mg/kg i.v. Phenylbutazone was less active ex vivo but did suppress chemotaxis by 23% (P<0.05) at 1h following an i.v. dose of 20mg/kg. It is suggested that part of the anti-inflammatory action of flunixin in dogs may be attributed to inhibition of PMN recruitment.
M. Krogsgaard Thomsen, Department of Pharmacology, Leo Pharmaceutical Products, DK-2750, Ballerup, Denmark.     

Involvement of opioidergic and alpha2-adrenergic mechanisms in the central analgesic effects of non-steroidal anti-inflammatory drugs in sheep

The level within the central nervous system where non-steroidal anti-inflammatory drugs (NSAIDs) produce analgesia and the mechanisms by which they mediate this effect are still uncertain. This study assessed the central analgesic effects of ketoprofen, phenylbutazone, salicylic acid and tolfenamic acid in sheep implanted with indwelling intrathecal (i.t.) catheters and submitted to mechanical noxious stimulation. The sheep received i.t. cumulative concentrations (0.375-200 microM; 100 microL) as well as a single intravenous (i.v.) dose (3, 8, 10 and 2 mg/kg, respectively) of each NSAID. The sheep were also given i.t. naloxone (5.49 mM; 100 microL) and atipamezole (4.03 mM; 100 microL) prior to i.v. ketoprofen. None of the i.t. NSAIDs increased mechanical thresholds. Intravenously, only ketoprofen and tolfenamic acid raised the pain thresholds. The hypoalgesic effect of i.v. ketoprofen was prevented by i.t. naloxone or atipamezole. Although NSAIDs had no direct effect on the spinal cord, their analgesic action appeared to be spinally mediated.     

Actions of non-steroidal anti-inflammatory drugs on equine leucocyte movement in vitro

The direct effects of four non-steroidal anti-inflammatory drugs (NSAIDs) on equine polymorphonuclear (PMN) and mononuclear (MN) leucocyte movement were investigated using two in vitro assay systems. The Boyden chamber microfilter technique measures both chemokinetic and chemotactic locomotion, and the agarose microdroplet assay measures solely chemokinesis. Zymosan-activated plasma (ZAP) and the synthetic peptide N-formyl-methionyl-leucyl-phenylalanine (FMLP) were used as standard chemoattractants for PMN and MN leucocytes, respectively. The actions of six concentrations of each NSAID, indomethacin (50 microM-10 mM), phenylbutazone (10 microM-1 mM), oxyphenbutazone (2.5 microM-500 microM) and flunixin (0.1 microM-50 microM), in suppressing cell movement induced by ZAP and FMLP were investigated. All four drugs exerted inhibitory effects on induced movement of both cell types in the Boyden chamber assay, usually in a concentration-dependent manner, although oxyphenbutazone action on PMN cells occurred only at the highest concentration tested. Significant inhibition of PMN and MN cell locomotion was produced by indomethacin, flunixin and oxyphenbutazone, and inhibition of PMN movement by phenylbutazone occurred in the agarose microdroplet assay. Flunixin was the most potent of the four drugs investigated in both assay systems. The findings may be of importance to the use of phenylbutazone and flunixin as NSAIDs in equine medicine, since the concentrations used were similar to concentrations of both drugs and the phenylbutazone metabolite oxyphenbutazone previously reported to occur in equine plasma and inflammatory exudate.     

Clinical pharmacology and therapeutic uses of non-steroidal anti-inflammatory drugs in the horse

Weak organic acids possessing anti-inflammatory, analgesic and antipyretic properties--commonly known as aspirin-like drugs--have been used in equine medicine for almost 100 years. These non-steroidal anti-inflammatory drugs (NSAIDs) may be classified chemically into two groups; the enolic acids such as phenylbutazone and carboxylic acids like flunixin, meclofenamate and naproxen. All NSAIDs have similar and possibly identical modes of action accounting for both their therapeutic and their toxic effects. They block some part of the cyclo-oxygenase enzyme pathway and thereby suppress the synthesis of several chemical mediators of inflammation, collectively known as eicosanoids. The available evidence indicates that some of the newer NSAIDs have a reasonable safety margin but further studies are required. The toxicity of phenylbutazone in the horse has been investigated very thoroughly in recent years and it has been shown to cause renotoxicity and, most significantly, ulceration of the gastrointestinal tract when relatively high doses are administered. Several factors may predispose towards phenylbutazone toxicity in the horse, including breed and age, but high dosage is considered to be particularly important. The absorption into, and fate within, the body of NSAIDs are considered and particular attention is drawn to the ways in which these pharmacokinetic properties relate to the drugs' toxicity and clinical efficacy. In reviewing current knowledge of the clinical pharmacology of this important group of drugs, it is hoped to provide the clinician with a rational, scientific basis for their safe and effective use in equine practice.     

非甾体抗炎药在猫临床疼痛管理中的应用

疼痛是猫常见且多发的问题,诱发原因很多。近几年,随着国内外兽医对宠物猫的慢性疼痛问题以及临床中疼痛管理日益重视,疼痛管理已成为临床兽医必须面对的重要课题之一。非甾体抗炎药因其解热、抗炎和镇痛的特性而逐渐被广泛应用于动物医学。国内有关非甾体类抗炎药在猫临床疼痛管理中的应用少见报道。主要就国外发表的一些关于猫长期使用非甾体抗炎药的相关文献进行综述,以期为非甾体抗炎药在猫临床疼痛管理中的进一步应用提供参考。     

Steroidal and non-steroidal anti-inflammatory drugs for wounds and traumatic inflammation

Abstract

Extract

Wounds of the skin and underlying tissues are common problems in both large and small animal practice, are frequently infected, and must therefore heal by granulation. This process is often impaired by movement, irritation, infection, necrosis, poor circulation, and even the inflammatory process itself. The latter, with its traditional cardinal signs, reflects the mobilization of the body's defences necessary for ultimate resolution. The as sociated pain, swelling, and interference with function may, however, have adverse effects. The clinician is thus faced with the need to maintain a delicate balance between adequate tissue defence, healthy granulation and repair on the one hand, and excessive or chronic inflammation, pain, swelling, impaired function, and circulation on the other. The therapeutic regimen, in addition to specific surgical procedures, should manipulate such target areas as etiologic factors, including those secondary to the initial insult, the mediators of inflammation, the non specific inflammatory process, and reparative processes. Such a regimen can well necessitate a “therapeutic cocktail”. During the last several years, work has been conducted on various anti-inflammatory (steroidal and non-steroidal) drugs, dimethyl sulphoxide (DMSO), and antihistamines(10) Jones, E. W. and Hamm, D. 1976. The Use of Naproxen in Horses. British Equine Journal (Pending),  [Google Scholar] (11) Kilian, J. G., Jones, E. W., Hamm, D., Riley, W. F. and Averkin, E. 1974. Proc. 20th Annual Mtg. Am. Assoc. of Equine Practitioners,  [Google Scholar]. This pharmacological polyglot, along with the complexity of inflammation, has created a need to clarify a confusing interaction and to justify the logic of utilizing such drugs either alone or in combination. It is in this context that controlled evaluations of parenteral and topical combinations of drugs in the horse, dog and cat have been conducted.     

The economic effects of trypanosomiasis in sheep and goats at a range research station in Kenya

Summary A study on the economic effects of naturally acquired trypanosomiasis in sheep and goats over a period of 35 weeks under range conditions in the Kiboko area of Kenya indicated that the financial loss from reduced weight gain and death amounted to 36·2 and 62·9 Kenya shillings per head for goats and sheep respectively. This was derived from the weight loss through death together with the reduced weight gain of the survivors compared with treated animals. The study also compared the efficacy of 3 drug regimes in goats and suggests that although quinapyramine (prophylactic) B.vet.C. provided the longest protective period, the weight increase of the stock under isometamidium chloride treatment was higher. The benefits of the drugs used are discussed.

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Los Efectos Economicos De La Tripanosomiasis En Ovejas Y Cabras En Kenya

Resumen Se llevó a cabo un estudio económico, sobre los efectos de la tripanosomiasis adquirida en forma natural, en ovejas y cabras en el área de Kiboko en Kenya. El estudio tuvo una duración de 35 semanas bajo condiciones de campo. Los resultados indicaron, que la pérdida monetaria debida a bajos aumentos de peso y muertes, tuvo un monto de 36.2 chelines (moneda de Kenya) por cabeza para cabras y ovejas respectivamente. Como parte del estudio, se comparó la eficacia de tres regímenes quimioprofilácticos y quimioterapéuticos en cabras. La quinapiramina (profiláctica) B vet C proporcionó el período más largo de protección, pero el incremento de peso de los animales bajo tratamiento con cloruro de isometamidio fue mayor. Se discuten los beneficios de las drogas usadas.

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Les Effets Economiques Des Trypanosomoses Chez Les Moutons Et Les Chevres Au Kenya

Résumé Une étude sur les incidences économiques des trypanosomoses naturellement acquises par des chèvres et des moutons entretenus sur des pâturages naturels pendant 35 semaines, dans le région de Kiboko au Kenya montrent que les pertes financières par perte de poids et mortalité atteignent respectivement 36,2 et 62,9 shillings kenyans par tête. L'étude a également porté sur l'efficacité relative de trois traitements médicamenteux chez les chèvres; il en résulte que bien que la quinapyramine (prophylactique) B et C donne une protection de plus longue durée l'augmentation de poids chez les animaux traités au chlorure d'isometamidium a été plus élevée.Les bénéfices résultent de l'utilisation de ces corps sont discutés.

     

The economic effects of trypanosomiasis in sheep and goats at a range research station in Kenya

A study on the economic effects of naturally acquired trypanosomiasis in sheep and goats over a period of 35 weeks under range conditions in the Kiboko area of Kenya indicated that the financial loss from reduced weight gain and death amounted to 36.2 and 62.9 Kenya shillings per head for goats and sheep respectively. This was derived from the weight loss through death together with the reduced weight gain of the survivors compared with treated animals. The study also compared the efficacy of 3 drug regimes in goats and suggests that although quinapyramine (prophylactic) B.vet.C. provided the longest protective period, the weight increase of the stock under isometamidium chloride treatment was higher. The benefits of the drugs used are discussed.     

Effect of steroidal and non-steroidal anti-inflammatory drugs on inflammatory markers in calves with experimentally-induced bronchopneumonia

The influence of treatment with steroidal (SAIDs) and non-steroidal (NSAIDs) anti-inflammatory drugs on inflammatory markers in thirty, 6-8 week old calves with induced bronchopneumonia was investigated. Animals received a single intravenous treatment with meloxicam (0.5 mg/kg body weight), flumethasone (0.05 mg/kg body weight) or sterile 0.9% NaCl (10 ml per animal). Body temperature, respiratory and heart rate, concentration of prostaglandins PGE2, PGF2alpha, thromboxane (TXB2), leukotriene (LTB4) and malonyldialdehyd (MDA) and proinflammatory cytokines i.e. tumor necrosis factor (TNFalpha) and interferon (INFalpha) were recorded in serum, bronchoalveolar lavage (BAL) and blood platelets (BP). A significant reduction of main inflammatory mediators PGE2, PGF2alpha,TXB2 and MDA after meloxicam treatment in calves with induced bronchopneumonia indicates a beneficial effect on the inflammatory processes. Contrary to effects observed by flumethasone, meloxicam induced an increase of LTB4 and INFalpha indicating that it is not immunosuppressive.     

Effects of non-steroidal anti-inflammatory drugs on the hyperalgesia to noxious mechanical stimulation induced by the application of a tourniquet to a forelimb of sheep

A tourniquet was used in conjunction with a mechanical threshold testing device to investigate the suitability of the technique for the investigation of analgesic drugs in sheep. The changes to the mechanical thresholds to noxious stimulation during and after the inflation of a pneumatic tourniquet on a limb were recorded, and the influence of pre-treatment with two non-steroidal anti-inflammatory drugs was studied. Fentanyl, an opioid agonist with known analgesic properties in sheep, was used as a positive control. The tourniquet significantly reduced the mechanical thresholds on the ipsi- but not the contralateral limb. Pretreatment with either flunixin meglumine or carprofen attenuated the development of mechanical hyperalgesia, and fentanyl initially caused a significant anti-nociceptive effect. The time to aversion was not significantly different between the treatments. These results suggest that hyperalgesia induced by a tourniquet may be a useful technique for the investigation of the anti-nociceptive effects of analgesic drugs in sheep.     

Modulatory effects of non-steroidal anti-inflammatory drugs on the luminol and lucigenin amplified chemiluminescence of equine neutrophils

The purpose of this study was to explore the potential modulation of equine neutrophil oxidative burst by a series of classical NSAIDs which was subsequently monitored by the luminol or lucigenin-enhanced chemiluminescence (CL) technique. A significant dose-dependent inhibition of the luminol CL was observed with the majority of investigated drugs. This inhibition was very significant for phenylbutazone and Indomethacin; while for aspirin, a higher concentration is required. The action of Ketoprofen was significant during the first 5 min and only when the concentration was above 1 mM. Indomethacin and acetylsalicylic acid result in an inhibition dose-dependent of luminol CL. On the other hand, the phenylbutazone showed an inhibiting effect when used either luminol or lucigenin though luminol is slightly better. When the ketoprofen is considered, an inhibiting effect of luminal CL was observed but less significant than the other NSAIDs investigated. The flunixin meglumine enhances strongly the CL.     

The interaction between orally administered non-steroidal anti-inflammatory drugs and prednisolone in healthy dogs

The interaction between oral non-steroidal anti-inflammatory drugs (NSAIDs) and prednisolone administered concurrently for 30 days was studied in 18 healthy dogs divided into 3 groups of 6 dogs each: a drug-free negative control group (NC group) given 2 gelatin capsules; a group given meloxicam (0.1 mg/kg) and prednisolone (0.5 mg/kg) (MP group); and a group given a reduced dosage of ketoprofen (0.25 mg/kg, p.o.) and prednisolone (0.5 mg/kg, p.o.) (KP group). The dogs were periodically monitored by physical examinations, blood analyses, endoscopic examinations, fecal occult blood tests, renal function tests [effective renal plasma flow (ERPF) and glomerular filtration rate (GFR)], urinalyses [urinary sediments, and urinary micro-albumin to creatinine ratio (UAlb/Cre)], urinary enzyme indices, and haemostatic function tests [buccal mucosa bleeding time (BMBT), cuticle bleeding time (CBT)]. Significant changes were observed in the KP group, including a decrease of ERPF and GFR, an increased UAlb/Cre ratio, prolonged BMBT and CBT, as well as the presence of more severe grades of endoscopic lesions and fecal occult blood. In both the MP and KP groups, abnormal enzymuria with exfoliation of renal tubular epithelial cells in the urine was found. However, no significant changes in any of the other tests were observed in the MP group compared with the NC group. These findings suggest that the combination of NSAIDs, even selective COX-2 inhibitors, with prednisolone may be contraindicated due to the potential for serious adverse effects on the kidneys, the platelets, and the gastrointestinal tract.     

Pharmacology and therapeutics of non-steroidal anti-inflammatory drugs in the dog and cat: 2 Individual agents

The general pharmacology of the non-steroidal anti-inflammatory drugs (NSAIDs) used in dogs and cats has been described in part 1 of this review (Lees and others 1991). This paper outlines the properties of the individual agents as they are used in small animal practice. The NSAIDs which have been used extensively in small animals include the older agents such as Aspirin, cinchophen and phenylbutazone. These agents have previously been used empirically by extrapolation of dosages from other species and by clinical experience. Studies are now available which provide a scientific rationale for the dosage rate recommended. A number of new drugs have recently been licensed for use in the dog or may be licensed in the near future. These include flunixin, carprofen and tolfenamic acid and the data generated from these products provides very useful information for formulating I effective dosage regimens. There are also some NSAIDs such as piroxicam which have been investigated in the dog because they have particular properties which may be of use in common clinical conditions and others, such as Paracetamol and Ibuprofen, which are readily available to the public and which owners may administer to dogs or cats at toxic doses.