HEAT hydrochloride

Multicenter phase II trial of the heat shock protein 90 inhibitor, retaspimycin hydrochloride (IPI-504), in patients with castration-resistant prostate cancer.[Pubmed:21762967]

Urology. 2011 Sep;78(3):626-30.

OBJECTIVE: To evaluate clinical activity and safety of retaspimycin hydrochloride (IPI-504) in patients with castration-resistant prostate cancer (CRPC). METHODS: A single-arm trial was conducted in 2 cohorts: group 1, chemotherapy naive; group 2, docetaxel-treated. IPI-504 was administered intravenously at 400 mg/m2 on days 1, 4, 8, and 11 of a 21-day cycle. Trial expansion was planned if >/=1 prostate-specific antigen (PSA) or radiographic response was noted per cohort. Pharmacokinetic samples were collected after the first dose; safety was assessed throughout. RESULTS: A total of 19 patients were enrolled (4 in group 1; 15 in group 2), with a median age of 66 years (range 49-78). Group 2 had received a median of 2 previous chemotherapy regimens. All group 2 patients had bone metastases; 66% had measurable soft tissue or visceral metastases. One group 1 patient remained on-trial for 9 cycles; his PSA level declined 48% from baseline. No PSA response was observed in the other patients. Adverse events reported in >25% of the study population included nausea (47%), diarrhea (42%), fatigue (32%), anorexia (26%), and arthralgia (26%). Two patients in group 2 died on-trial, involving study drug-related events of hepatic failure and ketoacidosis, respectively. CONCLUSION: Heat shock protein 90 inhibition with IPI-504 administered as a single agent had a minimal effect on the PSA level or tumor burden and was associated with unacceptable toxicity in several patients. Therefore, additional evaluation in CRPC patients is not warranted. IPI-504 is being investigated at less-intensive doses and schedules in other tumor types.

Effects of feeding dry-rolled corn-based diets with and without wet distillers grains with solubles and zilpaterol hydrochloride on performance, carcass characteristics, and heat stress in finishing beef steers.[Pubmed:25023799]

J Anim Sci. 2014 Sep;92(9):4023-33.

Zilpaterol hydrochloride (ZH) has been approved for use since 2006; however, there is no research on any interactions between ZH and coproducts. Additionally, there is no published information on the potential effects of ZH on heat stress in feedlot cattle. Therefore, an experiment was conducted to determine the effects of feeding dry-rolled corn (DRC)-based diets with and without wet distillers grains with solubles (WDGS) and ZH on performance, carcass characteristics, and heat stress in feedlot cattle. Four hundred thirty-eight steers were used in a randomized complete block design with a 2 x 2 factorial arrangement of treatments in 16 pens with 26 to 28 steers in each pen. Factors consisted of inclusion of 0 or 30% (on a DM basis) WDGS and inclusion of ZH at 0 or 84 mg/steer daily for 21 d at the end of the finishing period. Therefore, cattle were blocked by BW and randomly assigned to 1 of the resulting 4 treatment combinations: 1) DRC-based diet with 0% WDGS and 84 mg/steer ZH, 2) DRC-based diet with 0% WDGS and no ZH, 3) DRC-based diet with 30% WDGS and 84 mg/steer of ZH, and 4) DRC-based diet with 30% WDGS and no ZH. Final live BW, carcass-adjusted BW, ADG, and G:F were greater for cattle fed ZH than non-ZH-fed cattle (P < 0.01). Additionally, cattle fed ZH consumed 7.4% less DM than cattle not fed ZH (P < 0.01). Cattle fed ZH for 21 d also had a 2.9% greater HCW (P < 0.01), a 1.1% greater dressing percentage (P < 0.01), 7.3% greater LM area (P < 0.01), and an 8.4% improvement in yield grade (P < 0.01) than cattle not fed ZH. For the main effect of WDGS inclusion, ADG was greater for cattle fed 0 vs. 30% WDGS (P = 0.04) and G:F also tended to be greater for cattle fed 0 vs. 30% WDGS (P = 0.07) for the 21-d ZH feeding period. However, when evaluated over the entire experiment, cattle fed 30 vs. 0% WDGS had a greater ADG and G:F (P < 0.01). Furthermore, cattle fed 30 vs. 0% WDGS had a greater dressing percentage and tended to have a greater amount of 12th rib fat (P < 0.07). Heat stress measurements were collected during the time cattle were fed ZH, from May 31 to July 12, 2013. The slopes for change in respiration rate and panting score per day were positive but were not different across dietary treatments (P > 0.71); in addition, the slopes for change in respiration rate and panting score when accounting for environmental conditions were positive but were not different across dietary treatments (P > 0.32).

Effects of zilpaterol hydrochloride and soybean oil supplementation on feedlot performance and carcass characteristics of hair-breed ram lambs under heat stress conditions.[Pubmed:24496845]

J Anim Sci. 2014 Mar;92(3):1184-92.

Forty Dorper x Pelibuey ram lambs initially weighing 31.7 +/- 2.30 kg were stratified by BW and randomly assigned to treatments under a completely randomized design with a 2 x 2 factorial arrangement of treatments to evaluate effects of zilpaterol hydrochloride (ZH; 0 or 10 mg/lamb daily) and soybean oil (SBO; 0 or 6%) on feedlot performance, carcass characteristics, and wholesale cut yield of ram lambs under heat stress conditions. After a 34-d feeding period, all lambs were harvested. Climatic conditions were of moderate heat stress (average temperature 35.7 degrees C) for lambs during the study. Interactions ZH x SBO were not observed (P >/= 0.11) for any of the variables evaluated. During the first 17 d of experiment, ZH increased (P /= 0.06) by ZH supplementation. Leg yield (P = 0.01) and plain loin (P = 0.04) decreased with ZH and yields of other wholesale cuts were not affected (P >/= 0.10) by ZH. Feedlot performance (P >/= 0.20) and wholesale cut yield (P >/= 0.21) were not affected by SBO. Additionally, dressing percentage decreased (P < 0.01) with SBO while other carcass characteristics (P >/= 0.12) were not affected by SBO. In conclusion, inclusion of both ZH and SBO in feedlot finishing diets did not improve feedlot performance, carcass characteristics, or wholesale cut yield of hair-breed ram lambs under moderate heat stress. Feedlot performance responded only to ZH and only during the first 17 d of the feeding period. In addition, some carcass characteristics of economic importance, such as dressing, LM area, and leg yield, were improved by ZH.

Effects of shade and feeding zilpaterol hydrochloride to finishing steers on performance, carcass quality, heat stress, mobility, and body temperature.[Pubmed:26641190]

J Anim Sci. 2015 Dec;93(12):5801-11.

Steers ( = 480; 22% with black hides and 78% with red hides) were used to study the effects of shade and feeding zilpaterol hydrochloride (ZH) on performance, carcass quality, heat stress, mobility, and body temperature (BT). A randomized block design with a 2 x 2 factorial treatment arrangement was used with 4 replicates per treatment. Factors included housing type (open or shaded pens) and the feeding of ZH (0 or 8.33 mg/kg DM) the last 21 d on feed with a 3-d withdrawal. Cattle were blocked by BW into a heavy or light block and randomly assigned to pen within each block. Rumen boluses to record BT were inserted before ZH feeding. Respiration rate and panting scores were recorded daily during the ZH feeding period. Mobility scores were collected at various time points from before ZH feeding through harvest. Interactions between ZH and housing type were not significant ( > 0.26) for animal performance, carcass characteristics, and respiration or panting score. No differences ( > 0.44) were observed for DMI, ADG, or G:F on a live basis due to ZH; however, cattle fed in open pens tended ( = 0.08) to have a greater ADG than cattle in shaded pens. Cattle fed ZH had 14 kg heavier carcasses with larger LM area ( < 0.01) than control cattle. Respiration rates for cattle fed ZH were greater ( = 0.05) with no differences ( = 0.88) due to housing. Time affected ( < 0.01) mobility scores, with observations on the morning of harvest at the abattoir being the worst for all groups of cattle. An interaction ( < 0.01) was observed between ZH and housing type for BT. Cattle fed ZH, in both shaded and open pens, had lower ( < 0.05) average, maximum, and area under the curve BT than control cattle fed in the same housing type. However, the observed reduction in BT due to ZH was greater for cattle fed ZH in open pens than for cattle fed ZH in shaded pens. From these results, we conclude that ZH improved HCW with little impact on heat stress or mobility, suggesting that animal welfare was not affected by feeding ZH for 21 d at the end of the feeding period.