Renal replacement therapy in healthy adult horses.

BACKGROUND: Renal replacement therapy (RRT) has been implemented extensively in people to facilitate recovery from acute renal failure (ARF). RRT has not been explored in horses, but might provide a further treatment option in horses with ARF. OBJECTIVE: To investigate efficacy and safety of RRT in horses. ANIMALS: Five healthy adult horses. METHODS: A prospective study was performed on horses restrained in stocks and intravenously connected to a commercial RRT machine to allow continuous venovenous hemodiafiltration to be performed for 6 hours. The RRT machine was set at the following flow rates: blood flow rate 250 mL/min; dialysate rate 3,000 mL/h; prefilter replacement pump 3,000 mL/h; and postfilter replacement pump rate 2,000 mL/h. Balanced electrolyte solution was used as dialysate and replacement fluid. Heart rate, respiratory rate, body temperature, direct arterial blood pressure, urine output, and various clinicopathologic parameters were measured over the study period. RESULTS: Renal replacement therapy was successfully performed in horses, resulting in a mean creatinine clearance of 0.127 mL/kg/min (68.9 mL/min) and urea reduction ratio of 24%. No adverse effects were detected although a significant decrease in rectal temperature was observed (P ≤ .007). A significant increase in serum phosphorus (P ≤ .001) and decrease in BUN (P < .001) were also noted. A significant prolongation of prothrombin (P < .01) and partial thromboplastin time (P < .0001) were observed along with a decrease in platelet count (P ≤ .04). CONCLUSIONS AND CLINICAL IMPORTANCE: Renal replacement therapy can safely and effectively be used in adult horses.

Effect of direct injection of melanin-concentrating hormone into the paraventricular nucleus: further evidence for a stimulatory role in the adrenal axis via SLC-1.

Melanin-concentrating hormone (MCH) is implicated in the control of a number of hormonal axes including the hypothalamic-pituitary adrenal (HPA) axis. Previous studies have shown that there is evidence for both a stimulatory and an inhibitory action on the HPA axis; therefore, we attempted to further characterize the effects of MCH on this axis. Intracerebroventricular injection of MCH increased circulating adrenocorticotropic hormone (ACTH) at 10 min post injection. Injection of MCH directly into the paraventricular nucleus (PVN) was found to increase both circulating ACTH and corticosterone 10 min after injection. Additionally, MCH was found to increase corticotropin-releasing factor (CRF) release from hypothalamic explants, and this effect was abolished by the specific SLC-1 antagonist SB-568849. Neuropeptide EI, a peptide from the same precursor as MCH was also found to increase CRF release from explants. These results suggest that MCH has a stimulatory role in the HPA axis via SLC-1, and that MCH exerts its effects predominantly through the PVN CRF neuronal populations

Anti-infective research.

The biennial International Congress of Chemotherapy was hosted jointly by the British Society for Antimicrobial Chemotherapy and the International Society of Chemotherapy. This report covers, in the main, the plenary lectures as well as some sessions relating to anti-infective research.

Society for Anti-infective Pharmacology--Ninth International Symposium. 3-4 July 1999, Birmingham, UK.

This meeting, organized as a 'self-contained' pre-symposium to the 21st International Congress of Chemotherapy, was introduced by Paul Tulkens (Université Catholique de Louvain, Brussels, Belgium), the outgoing president of the society, who reviewed the progress of pharmacodynamics (PD) and pharmacokinetics (PK) in anti-infective research over the past ten years. It was noted that, hitherto, the factors driving therapeutic regimens have been largely 'irrational' with a concentration on achieving the lowest dosage, PK being used principally to establish drug presence and PD considerations largely 'terra incognita'. In contrast, through recent PK/PD studies, we now know that the dose effect of different classes of anti-infectives varies widely, with some showing time-dependence, some a post-antibiotic effect and some co-operating with host defenses. By integrating these factors, we should be in a better position to predict the success or failure of potential new antibiotics at an earlier stage. The focus of the meeting was, therefore, the use of PD and PK to accelerate drug discovery, development and registration. Two particular factors were stressed: the need to establish dosing regimens which avoided or minimized the development of resistance and the role of PD/PK in the discovery process for novel classes of antibiotics that are emerging from genomic programs. The conference was attended by approximately 50 participants, from academia and industry, with representatives from several regulatory authorities also present.