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1.
To investigate useful biomarkers associated with proximal tubular injury, we assessed changes in levels of a focused set of biomarkers in urine and blood. Male rats administered a single dose or four doses of gentamicin (GM, 240 mg/kg/day) or a single dose of cisplatin (CDDP, 5 mg/kg) were euthanized on days 2 (the day after initial dosing) 5, or 12. At each time point, histopathological examination of the kidney and immunohistochemistry for biomarkers, kidney injury molecule-1 (Kim-1), lipocalin (NGAL), clusterin (CLU), cystatin C (CysC) and β2-microglobulin (β2M) were performed. Biomarker levels were measured in urine and blood. In both treatment groups, degenerated/necrotic proximal tubules and regenerated tubules were mainly observed on days 5 and 12, respectively. At the same time as these tubular injuries, urinary Kim-1, CysC and β2M levels were increased. Moreover, urinary levels of CysC and β2M in GM-treated animals and Kim-1 in CDDP-treated animals increased (on day 2) prior to tubular injury on day 5. This was considered to reflect the characteristics of drug toxicity. Although almost all of the biomarkers in blood were not sufficiently sensitive to detect proximal tubular injury, urinary and plasma β2M levels simultaneously increased. Therefore, in addition to urinary Kim-1, CysC and β2M levels, plasma β2M levels were also considered useful for detecting proximal tubular injury.  相似文献   

2.
Our investigation of the urine of grazing horses at the University of Kentucky shows that the mean pH level is about 7.9, and if their diet is supplemented with grain, it is about 7.4. There appears to be no significant effect of time of day or year on urine pH levels in horses. However, horses taken from pasture and supplemented with grain in a stalled environment show a slight decrease in urine pH. Additionally, we investigated the effects of storage on pH levels. Equine urine samples appear to be quite stable with regard to pH for 48h, but then show a marked increase. Urine pH can have a great effect on the urine concentration of some drugs and therefore, uncertainties can arise when data generated in grazing horses are compared or extrapolated to racing horses whose urine pH can be quite low. In an effort to simulate the drop in urine pH seen in some racing horses, we examined the effects of ammonium chloride, ascorbic acid, lactic acid and methionine on urine pH in research horses. Both oral and intravenous routes of administration were used. Although all agents tested showed varying degrees of efficacy, oral administration of ascorbic acid proved to be the safest and most effective agent to model the rapid acidification of urine seen in post race samples.  相似文献   

3.
The objective of this study was to describe the clinical findings, medical management, and outcomes of horses with sabulous cystitis, and to describe a high flow bladder lavage procedure in horses that are standing or under general anesthesia. The medical records of 13 horses diagnosed with sabulous cystitis via cystoscopy between 2013 and 2020 were reviewed. Geldings (92%) and Warmbloods (46%) were overrepresented. The most common presenting complaint was urinary incontinence (69%). Complete blood cell count, serum biochemistry profile and urine cytology results were non-specific. Six (46%) horses had various degrees of erosion, ulceration, and hemorrhage of the bladder mucosa. All horses were treated with bladder lavage either with standing sedation (n = 12) or general anesthesia (n = 2), as well as antimicrobials (54%), anti-inflammatory drugs (62%), bethanechol (15%), and phenazopyridine (15%). Most horses (85%) were discharged from the hospital, but only a small percentage (23%) was reported as having no urinary abnormalities on follow-up communication.Key clinical message:Copious bladder lavage with a high flow rate system could mitigate the acute clinical signs and improve the quality of life of horses with sabulous cystitis, but the prognosis for return to previous level of athletic performance and long-term survival is guarded.  相似文献   

4.
The simplest medication rule is a “no detectable level” rule. This rule is used in much of Europe and North America. The principal problem with this rule is that it is virtually impossible to give any guidance to horsemen as to when they should cease drug administration. Part of the reason for this is that the analyst can change the rule at will, simply by changing his detection method.A much more equitable rule is one that specifies a blood or urinary tolerance for a drug. When a tolerance is specified, changing the test method is of no significance, and guidelines can be given to horsemen to help them comply with the rule. The National Association of State Racing Chemists' tolerance for phenylbutazone is a classic example of such a rule.Both of these rules have the advantage that the event which defines the violation is objective and independently verfiable. In each case, the drug can be detected or quantitated by an independent analyst. Independent confirmation removes all doubt as to the scientific basis of the regulatory action.Time rules specify times prior to post during which drugs cannot be administered. While such rules read well and are easy to write, they are troublesome to enforce. This is because enforcement of a time rule depends not on a measured blood or urinary drug level, but rather on an analyst's opinion as to when the drug was administered. This opinion will always have a probability of error, which may be greater, for example, than the number of horses that the analyst tests per year. Under these circumstances, the horsemen's testimony may be correct, and the analyst's opinion incorrect, in a significant proportion of cases. No objective, independent check of the analyst's opinion is possible, and neither are contrary opinions independently verifiable. Such a regulatory process is unsatisfactory and may undermine the credibility of the analyst.Because of the technical difficulty and expense of medication control, the strategy of no control for some medications is an option which requires careful evaluation.  相似文献   

5.
The present study was undertaken to evaluate the diagnostic significance of various urinary variables to detect acute kidney injury (AKI) in Egyptian draft horses treated with phenylbutazone (PBZ) therapy. Medical records of 52 draft horses, with a history of musculoskeletal painful conditions and treated frequently with various daily doses of injectable PBZ, were reviewed. Of those 52 horses, 38 were enrolled in this study. AKI was tentatively diagnosed based on thorough history and clinical findings and in conjunction with multiple biochemical screening tests. Accordingly, diseased horses were categorized into two main groups; the first group included 14 horses with prerenal azotemia, whereas the second group included 24 horses with renal azotemia. Biochemically, urinary malondialdehyde, urinary gamma-glutamyl transferase/creatinine (Cr) ratio, urinary protein/Cr ratio, urinary glucose, urinary sodium, fractional excretion of sodium, and renal failure index were significantly higher (P < .05) in horses of group 2 than those of group 1. However, values of urinary Cr, urine/plasma Cr ratio, urinary urea, and urine/plasma urea ratio were significantly decreased (P < .05) in horses of group 2. Analysis of receiver operating characteristic curve showed high sensitivity and specificity of most tested urinary variables as well as their derived indices for detection of AKI in diseased horses. Our findings suggest that the examined urinary variables as well as their ratios are helpful in documenting AKI associated with PBZ nephrotoxicity in Egyptian draft horses; however, their interpretation should be done in the light of the specific clinical setting and in conjunction with a thorough clinical and physical examination.  相似文献   

6.
ABSTRACT

Aims: To compare urine urinary pH, blood pH and concentration of electrolytes in blood of healthy horses fed an anionic salt supplement to achieve diets with a dietary cation-anion difference (DCAD) of ?40 or 0?mEq/kg DM, with horses a fed a diet with a DCAD of 85?mEq/kg DM.

Methods: Eight healthy horses received each of three diets in a randomised crossover design. Diets consisted of grass hay and concentrate feed, with a varying amount of an anionic supplement to achieve a DCAD of 85 (control), 0 or ?40?mEq/kg DM. They were fed for 14 days each with a washout period of 7 days between. Urine pH was measured daily and blood samples were collected on Days 0, 7 and 14 of each study period for the measurement of pH and concentration of electrolytes.

Results: Four horses voluntarily consumed the anionic supplement with their feed, but four horses required oral supplement administration via dose syringe. During the study period mean urine pH was lower in horses fed diets with a DCAD of 0 (6.91; SD 0.04) and ?40 (6.83; SD 0.04) mEq/kg DM compared to the control diet (7.30; SD 0.04). Compared with horses fed the control diet, mean urine pH was lower in horses fed the 0 and ?40?mEq/kg DM diets on Days 1–12 and 14 (p?<?0.05) of the study period. On Day 13 it was only lower in horses fed the ?40?mEq/kg DM diet (p?<?0.01). Urine pH was similar for horses fed the 0 and ?40?mEq/kg DM diets (p?=?0.151). The DCAD of the diet had no effect on blood pH, ionised Ca or anion gap. Mean concentrations of bicarbonate in blood were affected by diet (p?=?0.049); they were lower when horses were fed the 0?mEq/kg diet relative to the control diet on Day 14.

Conclusions and clinical relevance: The anionic supplement reduced urine pH in horses fed diets with a DCAD of 0 or ?40?mEq/kg DM compared with 85?mEq/kg DM. However as urinary pH did not fall below pH 6.5, the pH below which calcium carbonate uroliths do not form, this reduction in urine pH is unlikely to be clinically significant. The supplement was variably palatable and showed minimal promise as an effective urinary acidifier at the doses administered in this study.  相似文献   

7.
Thirty healthy lameness-free horses were subjected to the Complete Freund's Adjuvant (CFA) (Sigma, St Louis, Mo) carpitis model, which was allowed to develop for 5 days. The horses were then stratified by model-induced deficit in lameness score, carpal flexion, stride length, and carpal circumference, and they were randomly assigned to 3 groups of 10 horses. The horses were treated with one of 3 treatments beginning on day 5: Group A (positive control) received PSGAG (Adequan, Luitpold Pharmaceuticals, Inc, Shirley, NY); Group B received a compounded solution of acetyl-d-glucosamine (Red Cross Drug, Blanchard, Okla); and Group C received a solution of chondroitin monosulfate (Chondroprotec, Neogen Corp, Lexington, Ky). All horses received the treatments by intramuscular injection every 4 days for 4 weeks and all doses were 500 mg/5 mL. On days 12, 19, 26, and 33, the primary outcome measures were taken for lameness score, carpal flexion, stride length, and carpal circumference. The study was blinded because the clinician evaluating the outcome measures was unaware of the treatment group assignments. The group means for percent recovery of model-induced deficits in these parameters was subjected to statistical analysis.PSGAG was significantly (P < .05) more effective in the recovery of model-induced deficits in all parameters than were chondroitin and glucosamine injectable solutions, and there was no significant difference between the 2 test drugs. In this test system, these 2 compounds, often sold as “generic” versions of PSGAG, were significantly less effective than PSGAG.  相似文献   

8.
REASONS FOR PERFORMING STUDY: Analysis of human hair for drug residues is being used increasingly as a diagnostic tool in the investigation of drug use and abuse. Hair analysis is complementary to urine/blood testing in that it can provide an extensive historical record of drug use, is noninvasive, impersonal and can facilitate retesting. However, the technique has not been studied in horses. HYPOTHESIS: That the systemic administration of drugs in horses could be identified by the detection of drug residues in hair. OBJECTIVE: To evaluate hair analysis as a potential retrospective diagnostic test for drug administration in horses by studying the deposition of systemically administered drugs in tail hair. METHODS: Tail hairs (n = 40-50) from 4 horses with known drug histories were washed, chopped into 3-5 mm fragments and extracted overnight, in 0.1 mol/l hydrochloric acid, prior to solid-phase extraction and analysis by high-performance liquid chromatography. Horse 1, a 3-year-old Thoroughbred colt (gastric ulcer), was treated for 14 days with omeprazole; Horse 2, a 3-year-old Thoroughbred colt (anaerobic infection), was treated for 5 days with metronidazole; Horse 3, an 8-year-old Thoroughbred gelding (sinusitis), was treated for 10 days with trimethoprim/sulphadiazine; and Horse 4, a 3-year-old Thoroughbred colt (respiratory infection), was treated for 5 days with procaine benzylpenicillin. RESULTS: Omeprazole was not detected in tail hair. Metronidazole was detected in tail hair at a concentration of 0.57 ng/mg, trimethoprim and sulphadiazine at concentrations of 9.14 and 2.26 ng/mg, respectively, and procaine at a concentration of 1.66 ng/mg. CONCLUSIONS: The data presented suggest that hair analysis may become a useable technique for the retrospective detection of drug administration in horses. POTENTIAL RELEVANCE: This technique could ultimately be used as part of a prepurchase veterinary examination to identify misuse of anti-inflammatory and sedative drugs, in an in-training testing programme to identify use of anabolic agents, or to provide evidence to support post race blood or urine test results. Clearly, more extensive research will be required to evaluate the effectiveness of the technique over a much broader range of drugs.  相似文献   

9.
Monitoring urine production, renal function, and drug concentration in plasma can be extremely valuable in the management of critically ill horses. Renal failure, either hemodynamically-mediated or nephrotoxic, is a very common problem in horses either at admission or during critical care treatment. Prompt treatment is required in order to prevent the renal failure from becoming a life-threatening problem. Drug monitoring is not only used to decrease the risk of nephrotoxic renal failure, but should be used to confirm that therapeutic blood levels of a drug are present. Monitoring therapeutic but less than toxic levels is particularly important in critically ill horses since the pharmacokinetics of many drugs is affected by the degree of illness.  相似文献   

10.
Four mares and four geldings of Quarter Horse and Thoroughbred breeding were used in two simultaneous 4x4 Latin square experiments to study the effects of dietary cation-anion balance (DCAB), defined as meq ((Na+K)-C1)/kg dry matter, on urinary pH and mineral excretion in exercised horses. Diets consisted of a pelleted concentrate of corn, soybean meal and cottonseed hulls fed with bermudagrass hay. Treatments with DCAB of +5 (Low, L), +107 (Medium Low, ML), +201 (Medium High, MH) and +327 (High, H), meq ((Na+K)-Cl)/kg dry matter were formed by supplementing diet L with calcium chloride and ammonium chloride, diet ML with calcium chloride and diet H with sodium bicarbonate and potassium citrate (Table 1). Diet MH was not supplemented and served as the control treatment. Horses were conditioned aerobically for 6 weeks using long, slow, distance (LSD) workouts. During the experimental periods, horses were subjected to a combined exercise regimen alternating LSD with an interval-training protocol 6 days/week. There was a significant (P<.01) treatment effect on urine pH; least squares means for L, ML, MH and H were 6.73, 7.17, 7.38, and 7.92. Horses consuming diet L excreted more calcium in the urine (P<.05) than those consuming MH or H. Least squares means for daily urine calcium excretion tended to be linear across treatments and ranged from 19.66 g/day for diet L to 9.12 g/day for diet H. Urinary chloride excretion was higher (P<.05) for L than for MH or H. Horses fed diet H excreted more sodium (P<.05) in urine than horses fed the other diets. Lowering DCAB, increases urinary calcium loss; depending on the level of calcium intake, this could lead to negative calcium balance in exercising horses.  相似文献   

11.
Urinary concentrations of gamma glutamyl transferase (GGT), alkaline phosphatase (AP), aspartate aminotransferase (AsAT), and alanine aminotransferase (AAT) were measured in 32 healthy horses (16 geldings and 16 females) at the same time on 2 consecutive days. The subjects were divided into 4 ages groups, each comprising 8 horses (4 of each sex). In 10 of the geldings, urine was collected continuously for 72 hours, with catheterized samples being obtained at 0800, 1400 and 2000 hours, and an aliquot of the pooled urine being taken every 24 hours. Urinary enzyme activity was found to be unrelated to serum concentrations of the same enzymes. There was no diurnal variation in the activity of the urinary enzymes. Neither the sex of the horses nor their age influenced urinary enzyme activity regardless of whether it was expressed in absolute terms or in reference to creatinine excretion Normal values of GGT and AP were determined to be 3.3 +/- 3.0 IU/L, (2.5 +/- 3.4 IU/g Cr); and 10.2 +/- 4.0 IU/L (6.7 +/- 3.9 IU/g Cr) respectively. Neither AAT or AsAT were present in detectable levels. The mean urine creatinine concentration of all horses was 1.56 +/- 0.42 g/L with no significant age or sex variation being evident.  相似文献   

12.
All horses diagnosed with duodenitis/proximal jejunitis (DPJ) at the Texas Veterinary Medican Center between January 1, 1987 and July 1, 1993 were included in a retrospective study to evaluate the therapeutic and prognostic value of bethanechol and metoclopramide as gastrointestinal prokinetic drugs in horses with DPJ treated at our clinic, and to compare the clinical outcome of horses with DPJ treated with these drugs and those with DPJ that were not treated. During the study period, 70 horses diagnosed with DPJ were admitted to the clinic. Of these 70 horses, 18(25.7%) were treated with bethanechol, metoclopramide, or both; 13 of the 18 treated horses received more than one dose of either drug. No adverse effects of treatment with these drugs were noted. A precise therapeutic plan and clinical benefit of bethanechol, metoclopramide, or both coul not be determined from this retrospective study. The use of these gastrointestinal prokinetic drugs in horses with DPJ appeared to have prognostic value. Horses that did not respond to treatment with these gastrointestinal prokinetic drugs within 24 hours were not discharged alive.  相似文献   

13.
Embryonic death plays an important role in infertility in mares, and most of embryonic mortality occurs at an early stage (before day 40) of pregnancy. Previous investigations focused on B-mode sonographic images to determine abnormal pregnancy; however, no study has provided a quantitative and objective method to diagnose embryonic death. Here we developed a new index, “Uterine Index,” using color Doppler sonography to describe alterations of uterine blood flow in physiological and pathological gestations during early gestation. Six Trotter mares were used in this study. The pregnancies were interrupted with a prostaglandin F2α (PGF2α) analog (tiaprost) at days 25, 30, and 40. Three gestations were investigated in each stage. After the PGF2α administration, these mares were examined every 8 hours until the embryonic vesicles were not visible on ultrasound. In the control group, three pregnancies were examined daily from days 12 to 60. The embryo size was measured in B-mode sonography, and the blood flow in uterine arteries was examined in Doppler ultrasound. The resistance index (RI) and uterine index (UI) were calculated. In the control group, the RI values of uterine artery were lower in pregnant side compared with that of the non-pregnant side from day 15 on, and the difference became greater as the pregnancy advanced (P < .05). The UI was close to 0 before week 3 and increased to approximately 10 after week 4. In the PGF2α-treated group, the UI values reduced from pregnancy level to approximately 0. As early as 32 hours before embryonic death, we observed a significant difference of UI values between control and treated mares. On the contrary, the embryo size of treated mares was not different from that of normal mares. Through the analysis of all recorded UI values, we suggest that the UI values 10 and 5 are good values for distinguishing normal pregnancy (UI >10) from embryonic death (UI < 5). If the UI values are located between 10 and 5, a reexamination at intervals of 1 to 3 days is recommended. Our findings demonstrate that the UI is a useful method to diagnose and predict embryonic death in mares by providing reliable and objective information.  相似文献   

14.
An investigation was undertaken to demonstrate whether therapeutic treatment with ACTH raises hydrocortisone (cortisol) levels in horse urine above the limit (1000 ng/ml) established by the International Conference of Racing Authorities with the aim of controlling the abuse of cortisol and ACTH in equine sports. ACTH (200 iu) was administered i.m. to 3 Thoroughbred horses; urine and blood samples were collected at intervals afterwards and analysed by an immunoenzymatic system (ELISA) and HPLC-MS. To ascertain post exercise cortisol levels in untreated horses, 101 urine and 103 serum samples were taken from horses immediately after racing and analysed by ELISA. The peak urine level of cortisol, detected 8 h after ACTH administration, was around 600 ng/ml using either ELISA or HPLC-MS. The peak serum cortisol concentration was found to be around 250 ng/ml by ELISA, but consistently less by HPLC-MS. Mean cortisol levels in post race horses were 135.1+/-72.1 ng/ml in urine and 90.1+/-41.7 ng/ml in serum. High levels of the metabolite 20beta-dihydrocortisol in urine and the cortisol precursor 11beta-desoxycortisol in serum were found. The latter showed high cross-reactivity with cortisol on ELISA. In our experiment, treatment with ACTH 200 iu i.m. did not raise urinary cortisol levels above the 1000 ng/ml threshold proposed by the ICRA.  相似文献   

15.
Postrace urine samples from thoroughbred horses were examined to compare osmolality and specific gravity between horses treated with furosemide and those not treated. Samples were assigned to groups in relation to reported medication (furosemide) status, race finish position, and distance of race. Urine osmolality was significantly (P <.05) lower in samples from horses treated with furosemide when compared with untreated horses. Specific gravity determinations are less precise at measuring urine osmolality at lower levels (1.01 g/ml or less). The measurement of osmolality is a superior method for determining the urine solute concentration and facilitating the regulation of furosemide.  相似文献   

16.
Disseminated intravascular coagulation (DIC) secondary to colic was diagnosed in 23 horses. Each horse was categorized retrospectively as to the cause of the colic based on surgical and/or necropsy findings: group 1 consisted of 14 horses with compromised intestine that required resection and anastomosis; group 2 consisted of 3 horses with nonstrangulating intestinal displacement and/or impactions; and group 3 consisted of 6 horses with colic associated with enteritis and/or colitis. Horses were considered to be affected with DIC if at least three of five hemostatic parameters were significantly abnormal: decreased antithrombin III (AT III) values, increased level of fibrin degradation products (FDP), thrombocytopenia, prolonged activated partial thromboplastin time, and prolonged prothrombin time. The most consistent hemostatic abnormalities were decreased AT III activity, increased FDP titers, and thrombocytopenia. Clotting times were more variable and did not always correlate with the presence of excessive hemorrhage. Excessive hemorrhage was present during surgery in seven horses and occurred within 1 to 12 hours after surgery in nine other horses. In addition to treatment of the primary disease, 19 horses received treatment for DIC consisting of heparin and/or plasma or fresh whole blood transfusions. Heparin alone was used in 12 horses. Heparin, in addition to fresh whole blood transfusions or fresh plasma, was administered to four horses. Three horses were treated with plasma alone. Four other horses were not treated specifically for the DIC. Eight horses (34%) survived the acute coagulopathy. Although a greater proportion of the surviving horses received heparin therapy (87.5%; 7/8) than did those that died (60%; 9/15), the difference was not statistically significant (P = 0.345).(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Background: Little information is available about experimental induction of leptospirosis in horses. Objectives: Determine serologic, hematologic responses of horses to Leptospira interrogans serovar Kennewicki infection. Animals: Four adult horses seronegative for leptospirosis. Methods: Experimental and observational study. Horses were challenged with an equine isolate of L. interrogans serovar Kennewicki at 2 different doses and different inoculation sites. After challenge, the horses were monitored for 60 days. Blood, urine, and aqueous humor samples were collected at intervals until euthanasia 60 days after infection. Results: Pyrexia (39.3–40°C) occurred as early as 1 day after challenge with 10 × 108Leptospira divided equally between topical ocular and intraperitoneal injection in 2 horses. Leptospires were recovered from the blood and urine but not from the aqueous humor of the 2 febrile horses. The sera of all 4 challenged horses developed microscopic agglutination test antibody after challenge and remained relatively constant for 21 days. Titer to cross‐reacting strains declined earlier than titer to the challenge strain. Conclusions: Clinical disease in experimentally infected horses can be mild or inapparent in Leptospira infected horses. Repeated serologic testing can allow recognition of the infecting serovar. In febrile horses, Leptospira can be isolated from blood while isolation from the urine can occur after fever has subsided.  相似文献   

18.
A gas chromatographic screening procedure for the non-steroidal anti-inflammatory group of drugs is described. The method invovles on-column methylation of the carboxylic acid group using trimethylanilinium hydroxide as the methylating reagent. Fifteen such drugs were studied. Eight of these were detected in urine collected from horses that had received these compounds orally and for these drugs, rates of urinary excretion are recorded. Seven other members of this group of drugs were shown to be detectable by this procedure but in these cases the drug was added to urine and not administered to the horse.  相似文献   

19.
This study investigated whether a single intra‐articular administration (IA) of dexamethasone (DEX) in horses at therapeutic dosage could exert a systemic effect by influencing the hypothalamic‐pituitary‐adrenal axis activity as a consequence of (limited) absorption and systemic distribution. The results indicated that DEX was detectable in urine collected 12–48 h after IA administration and that injection was accompanied by a reduced urine excretion of cortisol, 6β‐hydroxycortisol (6βOHF) and two other metabolites of cortisol lasting up to 48 h post‐DEX administration. The systemic effects in horses treated with DEX by IA route are similar to those that typically occur with short‐term treatment including the reduction in urinary cortisol concentration.  相似文献   

20.
An outbreak of neurologic disease associated with serologic evidence of equine herpesvirus type 1 (EHV-1) infection occurred in a herd of 46 riding school horses. Ataxia and paresis were observed in 14 geldings and 5 barren mares. Eight affected horses had distal limb edema, 1 horse had a head tilt, and 3 others had urinary incontinence. Other clinical signs included fever, depression, and inappetance in 30 horses. Seven horses with neurologic signs were treated with acyclovir. Serum neutralizing antibody titers against EHV-1 increased 4-fold between acute and convalescent samples or exceeded 1: 256 in 19 of 44 horses, confirming recent infection. A significantly greater proportion of horses that seroconverted were mares ( P = .014). Of the 19 horses exhibiting ataxia and paresis, 17 made a complete recovery, 1 made a partial recovery, and 1 was euthanized.  相似文献   

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