Cyclooxygenase (COX) inhibitors and the intestine

Nonsteroidal anti-inflammatory drugs (NSAIDs) have long been used for the treatment of pain and inflammation because of their inhibitory effects on cyclooxygenase (COX). For almost as long as NSAIDs have been in use, multiple adverse effects have been noted. Assessment of many of these adverse effects have been complicated because of the discovery of multiple splice variants of the cox gene, and a greater array of COX inhibitors, especially the COX-2 selective inhibitors have become available. Some of these adverse effects cannot be readily explained by the effect of these drugs on COX. This has sparked a new field of investigation into the COX-independent effects of the COX inhibitors. The major noncyclooxygenase targets of the COX inhibitors of particular relevance to inflammation and the gastrointestinal tract are phosphatidylinositol 3'-kinase Akt signaling, uncoupling of oxidative phosphorylation, PPARgamma, nuclear factor KB, mitogen activated protein kinases, and heat shock proteins.     

Mineral absorption in the black rhinoceros (Diceros bicornis) as compared with the domestic horse

To test whether mineral recommendations for horses are likely to guarantee adequate mineral provision for black rhinoceroses (Diceros bicornis), we investigated the apparent absorption (aA) of macro- and microminerals in eight black rhinoceroses from three zoological institutions in a total of 32 feeding trials with total faecal collection, with additional data from three unpublished studies (18 feeding trials). Feeds and faeces were analysed for Ca, P, Mg, Na, K, Fe, Mn, Cu, Zn and Co. The resulting aA coefficients, and the linear relationships of apparently absorbable dietary mineral content to total dietary mineral content [per 100 g dry matter (DM)], were compared with data for domestic horses. Rhinoceroses had significantly higher aA coefficients for Ca and Mg (because of a higher calculated 'true' absorption), and lower ones for Na and K (because of calculated higher endogenous faecal losses). High absorption efficiency for divalent cations is hypothesized to be an adaptation to a natural diet of particularly high Ca:P ratio (approximately 14:1); an effective removal of Ca from the ingesta guarantees sufficient P availability at the fermentation site in the hindgut. Higher faecal losses of Na and K are hypothesized to be linked to a higher faecal bulk per DM intake in black rhinoceroses as compared with horses because of a generally lower digestive efficiency. There were no relevant differences in the absorption patterns of microminerals. In particular, there were no discernable differences in Fe absorption within the rhinoceroses for diets with and without tannin supplementation. Several of the zoo diets assessed in this study were deficient in Cu, Mn or Zn, and most contained excessive levels of Fe when compared with horse requirements. The findings of this study indicate that differences in mineral absorption between occur even between species of similar digestive anatomy; that in particular, Ca absorption might vary between hindgut fermenters with Ca:P ratio in their natural diet; that Na might be a particularly limiting factor in the ecology of free-ranging rhinoceroses; that moderate doses of tannins do not seem to markedly influence mineral absorption; and that diets for captive animals should contain adequate, but not excessive mineral levels.     

A potentized homeopathic drug, Arsenicum Album 200, can ameliorate genotoxicity induced by repeated injections of arsenic trioxide in mice

Groundwater arsenic contamination has become a menacing global problem. No drug is available until now to combat chronic arsenic poisoning. To examine if a potentized homeopathic remedy, Arsenicum Album-200, can effectively combat chronic arsenic toxicity induced by repeated injections of Arsenic trioxide in mice, the following experimental design was adopted. Mice (Mus musculus) were injected subcutaneously with 0.016% arsenic trioxide at the rate of 1 ml/100 g body weight, at an interval of 7 days until they were killed at day 30, 60, 90 or 120 and were divided into three groups: (i) one receiving a daily dose of Arsenicum Album-200 through oral administration, (ii) one receiving the same dose of diluted succussed alcohol (Alcohol-200) and (iii) another receiving neither drug, nor succussed alcohol. The remedy or the placebo, as the case may be, was fed from the next day onwards after injection until the day before the next injection, and the cycle was repeated until the mice were killed. Two other control groups were also maintained: one receiving only normal diet, and the other receiving normal diet and succussed alcohol. Several toxicity assays, such as cytogenetical (chromosome aberrations, micronuclei, mitotic index, sperm head anomaly) and biochemical (acid and alkaline phosphatases, lipid peroxidation), were periodically made. Compared with controls, the drug fed mice showed reduced toxicity at statistically significant levels in respect of all the parameters studied, thereby indicating protective potentials of the homeopathic drug against chronic arsenic poisoning.     

Neuronal vacuolation, myelopathy and laryngeal neuropathy in a mixed-breed dog

A bilateral and symmetrical neuronal vacuolation associated with spinal cord white matter degeneration and laryngeal neuropathy was observed in a 12-week-old male mixed-breed dog with a history of progressive pelvic limbs ataxia. On clinical examination, signs included inspiratory stridor, spinal ataxia, tetraparesis, and proprioceptive deficits more severe in the pelvic limbs. Examination of the larynx showed bilateral laryngeal paralysis and electromyography revealed fibrillation potentials restricted to the intrinsic laryngeal muscles. Clinical and pathological findings resembled the syndrome of neuronal vacuolation and spinocerebellar degeneration described in Rottweiler dogs. This is the first report of a similar disorder in a dog different from Rottweiler.     

The reproductive performance of dairy cows with anovulatory anoestrus that were injected with either gonadotrophin-releasing hormone or oestradiol benzoate as part of a re-treatment process after insemination

This experiment compared the reproductive performance of synchronised anoestrous dairy cows that were treated initially with a combination of progesterone and oestradiol benzoate and then with either gonadotrophin-releasing hormone (GnRH) or oestradiol benzoate to resynchronise returns to service. It was hypothesised that injecting anoestrous dairy cows with GnRH 12-15 days after insemination and coinciding with the time of insertion of a controlled intravaginal progesterone-releasing (CIDR) device would increase conception rates to the preceding 1st insemination compared with oestradiol benzoate treated cows; both GnRH and oestradiol benzoate would resynchronising the returns to service of those cows that did not conceive to the preceding insemination. Groups of cows in 11 herds were presented for a veterinary examination after they had not been seen in oestrus postpartum. Those cows diagnosed with anovulatory anoestrus (n = 1112) by manual rectal palpation and/or ultrasonography were enrolled in the trial. Each enrolled cow was injected with 2 mg oestradiol benzoate i.m. on Day -10, (where Day 0 was the 1st day of the planned insemination) concurrently with vaginal insertion of a CIDR device. The device inserted was withdrawn on Day -2 and then each cow injected i.m. with 1 mg of oestradiol benzoate on Day -1 unless it was in oestrus. Observation for oestrus preceded each insemination. Every cow that had been inseminated on Days -1,0,1 or 2 was presented for treatment for resynchrony on Day 14 (n = 891). They were divided into 2 groups; those with an even number were each injected i.m. with 250 microg of a GnRH agonist (Treatment group n = 477); each of the cows with an odd number injected i.m. with 1 mg of oestradiol benzoate (control group, n = 414). Each GnRH or oestradiol benzoate injection preceded reinsertion of a CIDR device previously inserted from Days -10 to -2. It was withdrawn on Day 22, 24 hours before injecting 1 mg oestradiol benzoate. Cows observed in oestrus were submitted for a 2nd insemination. Every enrolled cow still present in the herd was pregnancy tested by palpation of uterine contents per rectum about 6 weeks later and again at the end of a herd's seasonal breeding programme. The alternative use of GnRH instead of oestradiol benzoate did not affect the percentage of cows conceiving within 3 days of the mating start date (MSD) (35.6 % vs 35.3 %, P = 0.90), resubmission rates for a 2nd insemination among cows not pregnant to the 1st insemination (81.6 % vs 83.5 %, P = 0.41), 6-week pregnancy rate (59.3 % vs 60.6 %, P = 0.65), 21-weekpregnancy rate (86.6 vs 85.0, P = 0.36), mean interval from MSD to conception (32.5 +/- 1.8 days vs 29.9 +/- 1.8 days, P = 0.26) or conception rate of cows reinseminated by Day 28 (43.3 % vs 38.8 %, P = 0.39). When GnRH was compared with oestradiol benzoate, it did not increase conception rates to the 1st service; it was as effective as oestradiol benzoate in synchronising returns to service in previously treated anoestrous cows that did not conceive to the 1st service. Its use affected neither conception rates to the preceding 1st inseminations nor to the following 2nd inseminations.     

ACTH stimulation test in the captive cheetah (Acinonyx jubatus)

Serum cortisol response was assessed in 8 captive cheetahs, of varying ages, after the intravenous administration of 500 microg of tetracosactide (Synacthen Depot, Novartis, Kempton Park) while maintained under general anaesthesia. In addition, 8 cheetahs were anaesthetised and given an equal volume of saline in order to establish baseline cortisol concentrations at similar stages of anaesthesia. A significant difference in the median cortisol concentration measured over time was found following ACTH administration in the ACTH group (P < 0.001). There was no difference between the median cortisol concentrations in the ACTH group at time-points 120, 150 and 180 min after ACTH stimulation (P = 0.867). Thus it appears appropriate to collect serum 120 to 180 min after tetracosactide administration to assess maximal stimulation of the adrenal in the cheetah. No statistically significant rise was seen in the anaesthetised control group following the injection of saline (P = 0.238).     

Repellent effects of the essential oil of Lavendula angustifolia against adults of Hyalomma marginatum rufipes

The repellent effects of the essential oil of Lavendula angustifolia on adults of Hyalomma marginatum rufipes was studied at concentrations of 5, 10 and 20% v/v. A suitable tick climbing bioassay based on the questing behaviour of ticks was used to test for repellency. High percentage repellency (range 70-100) was shown at all concentrations of the essential oil of L. angustifolia, although at 5% v/v it only persisted for the first 40 minutes compared with 120 minutes at other concentrations (10 and 20% v/v). The repellent strength of L. angustifolia compared well (P > 0.05) with that of DEET (N,N-diethyl-m-toluamide), a commercial reference repellent, for the 2-hour period of the study.     

Urinary catecholamine and metanephrine to creatinine ratios in healthy dogs at home and in a hospital environment and in 2 dogs with pheochromocytoma

BACKGROUND: Measurement of high concentrations of urine catecholamines and metanephrines is useful in diagnosing pheochromocytoma in humans. Stress increases catecholamine excretion in urine. HYPOTHESIS: Stress of a hospital visit increases urinary catecholamine and metanephrine excretion in dogs. ANIMALS: Fourteen clinically normal dogs, 2 dogs with pheochromocytoma. METHODS: Voided urine samples were collected by the owners 7 days before (t-7), during the hospital visit immediately after diagnostic procedures (t0), as well as 1 (t1) and 7 days (t7) after the hospital visit. Urine catecholamine and metanephrine concentrations were measured using high-pressure liquid chromatography and expressed as ratios to urine creatinine concentration. RESULTS: In client-owned dogs epinephrine and norepinephrine ratios at t0 were significantly higher compared with ratios at t7. Metanephrine and normetanephrine ratios at t-7, t0, and t1 did not differ significantly from each other; however, at t7 they were significantly lower compared to values at t-7. In staff-owned dogs no significant differences were detected among the different collecting time points for any variable. Metanephrine and normetanephrine ratios were significantly higher in client-owned dogs compared to staff-owned dogs at t-7, t0, and t1 but not at t7. CONCLUSIONS AND CLINICAL IMPORTANCE: Stress associated with a hospital visit and with the sampling procedure causes increases in urine catecholamine and metanephrine excretion. Urine collection for the diagnosis of pheochromocytoma probably should take place at home after adaptation to the sampling procedure.     

Serum C-reactive protein concentration as an indicator of remission status in dogs with multicentric lymphoma

BACKGROUND: The acute-phase protein C-reactive protein (CRP) is used as a diagnostic and prognostic marker in humans with various neoplasias, including non-Hodgkin's lymphoma. OBJECTIVE: To evaluate if CRP could be used to detect different remission states in dogs with lymphoma. ANIMALS: Twenty-two dogs with untreated multicentric lymphoma. METHODS: Prospective observational study. Blood samples were collected at the time of diagnosis, before each chemotherapy session, and at follow-up visits, resulting in 287 serum samples. RESULTS: Before therapy, a statistically significant majority of the dogs (P = .0019) had CRP concentrations above the reference range (68%, 15/22). After achieving complete remission 90% (18/20) of the dogs had CRP concentrations within the reference range, and the difference in values before and after treatment was statistically significant (P < .001). CRP concentrations of dogs in complete remission (median, 1.91; range, 0.2-103) were significantly different (P = .031) from those of dogs with partial remission (median, 2.48; range, 0-89), stable disease (median, 1.77; range, 1.03-42.65), or progressive disease (median, 8.7; range, 0-82.5). There was profound variation of CRP measurements within each dog. CONCLUSIONS: CRP is useful in determining complete remission status after treatment with cytotoxic drugs. However, the individual variation between dogs means CRP concentration is not sufficiently different in other remission states to permit its use in monitoring progression of the disease. Greater reliability in determining remission status might be achieved by combining CRP concentration with other serum markers.