C57BL/6J mouse superovulation: schedule and age optimization to increase oocyte yield and reduce animal use

Superovulation protocols have been described for different mouse strains, however the numbers of animals used are still high and still little information is known about hormone administration schedules and estrous cycle phases. In this study, we aimed to optimize a superovulation protocol by injecting 5 IU of pregnant mare serum gonadotropin followed by 5 IU of hCG 48 h later, using three different schedules related to the beginning of the dark cycle (3, 5 and 7 pm) in a light cycle of 7 am to 7 pm, with light on at 7 am. C57BL/6J mice at 3, 4 and 5 weeks of age were used and the estrous cycle phase for times of PMSG and hCG injections was also analyzed. Total oocyte number was counted in the morning after hCG injection. Hormones given at 3 weeks of age at 3 pm (59 ± 15 oocytes) and 7 pm (61 ± 10 oocytes) produced a significantly higher oocyte number compared with oocytes numbers collected from females at the same age at 5 pm (P = 0.0004 and <0.0001 respectively). Females at 4 and 5 weeks of age produced higher numbers of oocytes when superovulated at 7 pm. No statistical differences between females at different phases of the estrous cycle were found. These results showed that in C57BL/6J mice, hormones should be given at 3 or 7 pm for females at 3 weeks of age, however older females should be superovulated closer to the beginning of the dark cycle to reduce female mouse use and increase the numbers of oocytes produced per female.

ROLE OF THE PHARMACIST IN MANAGING HIGH BLOOD PRESSURE OF HYPERTENSIVE PATIENTS IN PRIMARY CARE UNITS

Objective: The aim of this study was to evaluate the influence of pharmaceutical care on the control of high blood pressure (BP) in hypertensive patients. Methods: The study included thirty hypertensive patients from primary or secondary healthcare located in the south of São Paulo, Brazil. Results: The majority of patients was aged over 60 years (68.75%), non-smokers (90%), non-alcoholics (93.33%), did not practice physical activities (93.33%), and presented comorbidities and polypharmacy. The most common drug-related problems were drug-drug interactions, missed doses, incorrect frequency or time of administration, incorrect patient administration technique, and self-medication. The interventions used during the pharmaceutical consultations (PC) were based on the organization of medicines with tools such as a pillbox organizer (84.38%). A significant improvement in BP control (p<0.05) was observed when comparing BP measurements before and after the PC; however, the number of PCs did not influence the BP reduction. Conclusion: Patient guidance and a simple intervention favor better patient understanding of medication administration schedules.

Timing of assessments for PRO measures in advanced RCC clinical trials.

e19101 Background: Efficient and thoughtful collection of PROs in randomized cancer trials is necessary, especially when comparing drugs with differing administration schedules. Assessment timing for PROs can dramatically influence results. We sought to better understand how different assessment schedules affect interpretation of toxicity using PRO data. Methods: We reviewed 3 randomized trials in advanced/metastatic RCC with a control arm of sunitinib administered 4 weeks on/2 weeks off. All 3 trials used FACT Kidney Symptom Index (FKSI-19 or -DRS) and one also used EORTC QLQ-C30. For each trial, we chose patient-reported diarrhea and bone pain due to their strong association with the therapeutic intervention and the disease, respectively. Results: For the first 12 weeks, all trials had PRO assessments at baseline but had differing schedules thereafter. PRO assessment in Trial 1 was every 3 weeks; Trial 2: week 6 and week 12; Trial 3: every 3 weeks on the investigational arm and at weeks 4, 6, 10 and 12 on the sunitinib arm. Notably, all assessments for Trial 2 were after 2-week sunitinib washout while Trials 1 and 3 had assessments before and after washout. The table shows the percentage of patients who experienced any worsening from baseline in diarrhea and bone pain in the first 2 assessments. In each trial, more patients had worsening following periods of treatment versus washout on the sunitinib arm, with no such fluctuation on the non-sunitinib arms. The pattern was more apparent for diarrhea (treatment-related) than for bone pain (disease-related). Conclusions: Patients’ recall of symptoms may vary depending on the timing of PRO assessments in relation to drug administration and may be more prominent with respect to treatment-related symptoms, as disease-related symptoms are less impacted by drug toxicity and washout. Clinical protocols should carefully consider PRO assessment timing in relation to drug administration to improve interpretation of toxicity. Higher fidelity PRO data can be obtained with weekly collection of symptoms during the first few months of cancer clinical trials. [Table: see text]

Tolerability and surrogate efficacy parameters of a polymerized depot mixture pollen extracts without dilutional effect

Aim: To evaluate tolerability of subcutaneous immunotherapy, in a polymerized mixture ( Olea europaea/ Phleum pratense) depot presentation. Patients & methods: A total of 47 poly-allergic patients received: an abbreviated schedule with three injections at weekly intervals or a cluster schedule with two administrations in 1 day. Both treatments continued with 3 monthly maintenance administrations. Results: Two systemic reactions, (4.3%). One grade 0 and one grade I. No local reactions. Immunoglobulin levels, increased significantly at final visit versus baseline in sIgG and sIgG4; in both schedules and allergens, no significant changes in specific immunoglobulin E levels were detected. Cutaneous reactivity at final visit decreased significantly. Conclusion: Both administration schedules with polymerized mixture of O. europaea/ P. pratense, presented an excellent tolerability profile and induced preliminary efficacy changes.