Pharmacokinetic and pharmacodynamic properties of pantoprazole in calves.

Introduction: Development of abomasal ulceration is a large concern, especially within calves; however, there is a paucity of research into the use of gastro protectants in ruminant species. Proton pump inhibitors, such as pantoprazole, are widely used in humans and companion animals. Their efficacy in ruminant species is undetermined. The objectives of this study were to 1) estimate the plasma pharmacokinetic parameters for pantoprazole in neonatal calves after three days of intravenous (IV) or subcutaneous (SC) administration, and 2) measure the effect pantoprazole had on abomasal pH over the treatment period. Methods: Pantoprazole was administered to 6 Holstein-Angus cross bull calves at a dose of 1 mg/kg (IV) or 2 mg/kg (SC), once a day (every 24 h) for three days. Plasma samples were collected over a 72 h period and analyzed via HPLC-UV for determining pantoprazole concentrations. Pharmacokinetic parameters were derived via non-compartmental analysis. Abomasal (n= 8) samples were collected via abomasal cannulas over a 12 h period, per calf per day. Abomasal pH was determined via a bench top pH analyzer. Results: Following Day 1 of IV administration, plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 199.9 mL/kg/h, 1.44 h, and 0.51 L/kg, respectively. On Day 3 of IV administration, the reported values were 192.9 mL/kg/h, 2.52 h, and 1.80 L/kg mL, respectively. Elimination half-life and volume of distribution (V/F) of pantoprazole following SC administration were estimated at 1.81 h and 0.55 L/kg, respectively, on Day 1; and 2.99 h and 2.82 L/kg, respectively, on Day 3. Discussion: The reported values for IV administration were similar to those previously reported in calves. SC administration appears to be well absorbed and tolerated. The sulfone metabolite was detectable for 36 h after the last administration for both routes. Abomasal pH was significantly higher than the pre-pantoprazole pH 4, 6, and 8 h after administration in both the IV and SC groups. Further studies of pantoprazole as a treatment/preventative for abomasal ulcers are warranted.

Pharmacokinetics of esomeprazole in goats (Capra aegagrus hircus) after intravenous and subcutaneous administration.

Background: Stressed and hospitalized goats are at risk of developing abomasal (gastric) ulceration, but there is a paucity of pharmacokinetic studies for proton pump inhibiting drugs, such as, esomeprazole in goats. Objectives: The objectives for this study were to estimate plasma pharmacokinetic parameters for esomeprazole in adult goats after intravenous (IV) and subcutaneous (SQ) administration. A secondary objective was to describe the plasma kinetics of the metabolite esomeprazole sulfone after IV and SC administration in goats. Materials and methods: Esomeprazole was administered to 5 adult goats in a crossover study at doses of 1 mg/kg IV or 2 mg/kg SC. Plasma samples were collected over 36 h and analyzed via reverse phase HPLC to determine concentrations of esomeprazole and esomeprazole sulfone. Pharmacokinetic parameters were derived via non-compartmental analysis. Results: Following IV administration, mean values for plasma clearance (Cl), elimination half-life [T1/2 (λz)], C0, and volume of distribution (V z ) of esomeprazole were estimated at 24.9 mL/min/kg, 6 min, 2.324 µg/mL, and 0.23 L/kg, respectively. After SC administration elimination half-life, maximum concentration (Cmax) and time to maximum concentration (Tmax) of esomeprazole were estimated at 29 min, 1.038 µg/mL, and 22 minutes respectively. Maximum concentrations of the sulfone metabolite were 32 and 18 ng/mL after IV and SC administration. Conclusion: Esomeprazole was rapidly eliminated from plasma after both IV and SC injection in goats. The elimination half-life in goats appears to be shorter than reported in dogs, as well as less than that reported for pantoprazole in goats. The sulfone metabolite was detected and also rapidly eliminated from the plasma after both IV and SC administration. Additional pharmacodynamic investigations are needed to determine the efficacy of esomeprazole on abomasal (gastric) acid suppression in goats and could include larger doses or additional routes of administration.

Pharmacokinetics of Pantoprazole and Pantoprazole Sulfone in Goats After Intravenous Administration: A Preliminary Report.

Background: Ruminant species are at risk of developing abomasal ulceration, but there is a lack of pharmacokinetic data for anti-ulcer therapies, such as the proton pump inhibitor pantoprazole, in goats. Objective: The primary study objective was to estimate the plasma pharmacokinetic parameters for pantoprazole in adult goats after intravenous administration. A secondary objective was to describe the pharmacokinetic parameters for the metabolite, pantoprazole sulfone, in goats. Methods: Pantoprazole was administered intravenously to six adult goats at a dose of 1 mg/kg. Plasma samples were collected over 36h and analyzed via reverse phase high performance liquid chromatography for determination of pantoprazole and pantoprazole sulfone concentrations. Pharmacokinetic parameters were determined by non-compartmental analysis. Results: Plasma clearance, elimination half-life, and volume of distribution of pantoprazole were estimated at 0.345 mL/kg/min, 0.7 h, and 0.9 L/kg, respectively following IV administration. The maximum concentration, elimination half-life and area under the curve of pantoprazole sulfone were estimated at 0.1 µg/mL, 0.8 h, and 0.2 hr*µg/mL, respectively. The global extraction ratio was estimated 0.00795 ± 0.00138. All animals had normal physical examinations after conclusion of the study. Conclusion: The reported plasma clearance for pantoprazole is lower than reported for foals, calves, and alpacas. The elimination half-life appears to be < that reported for foals and calves. Future pharmacodynamic studies are necessary for determination of the efficacy of pantoprazole on acid suppression in goats.

Developing a measure to assess identity reconstruction in patients with multiple sclerosis.

PURPOSE/OBJECTIVE: To develop and test initial validation of a theory-driven quantitative measure of identity reconstruction in patients with multiple sclerosis (MS) based upon previous qualitative research. Research Method/Design: This study uses a cross-sectional survey design, in which 137 patients living with MS were recruited from an outpatient MS Center in the Southeastern U.S. Participants completed demographic items, Identity Reconstruction Assessment Scales (IRAS), Patient Determined Disease Steps, Medical Outcomes Study Measures of Patient Adherence, Chronic Disease Self-Efficacy Scale, Hospital Anxiety and Depression Scale, Leeds MS Quality of Life Questionnaire, MS-Related Stigma Scale, and Posttraumatic Growth Inventory-Short Form. RESULTS: The IRAS conformed to a 3-factor solution consisting of 23 items accounting for 42.6% of the variance. The 3 factors, labeled as "sustained identity" (α = .84), "reactionary identity" (α = .74), and "integrated identity" (α = .65), were not significantly correlated with each other, necessitating and allowing for independent scoring of the scales. Higher scores on "sustained identity" scale were associated with less anxiety, depression, perceived disability, and MS-related stigma, as well as with increased self-efficacy, treatment adherence, and quality of life. "Reactionary identity" scale was positively correlated with anxiety and MS-related stigma. "Integrated identity" was significantly associated with age and perceived disability. CONCLUSIONS/IMPLICATIONS: Identity reconstruction provides needed context for understanding adjustment to and living with MS. Examination of the IRAS within a larger sample and in other disease groups can provide additional construct validity evidence. (PsycINFO Database Record

Testing the health promotion model for adherence and quality of life in individuals with multiple sclerosis.

The nature of multiple sclerosis (MS) presents challenges to health-promoting behaviors (e.g. adherence) and quality of life. The Health Promotion Model (HPM) proposes that these outcomes are explained by individual characteristics (i.e. biological, social, psychological) and behavior-specific cognitions (e.g. self-efficacy). The current study sought to test the HPM in explaining self-reported adherence and MS quality of life among 121 MS patients receiving care in an MS clinic in the southeastern United States. Hierarchical regression models partially supported the HPM for adherence (R2 = .27) and more fully for quality of life (QoL) (R2 = .64). Depression and stigma were among the variables most strongly related to both adherence and QoL; contrary to HPM theory, self-efficacy was not significantly related to adherence but was to QoL. Thus, the HPM may help to guide strategies used to improve QoL among individuals living with MS; however, the model may need further refinement to be used with adherence.

Perceptions of caregiver distress, health behaviors, and provider health-promoting communication and their relationship to stress management in MS caregivers.

This study applied the Stress/Health Model to examine a novel approach for promoting stress management among 67 caregivers of persons with multiple sclerosis, who often face unique caregiving challenges. Hierarchical regressions indicated that caregiver distress (i.e., emotional burden) and engagement in other health-promoting activities (i.e., controlling alcohol use) were the best predictors of caregiver stress management. Communication with the MS care recipient's health provider about caregiver engagement in health-promoting activities was associated with caregiver stress management, but not significantly more so than explained by the other factors (i.e., caregiver distress and engagement in health-promoting behaviors). A more controlled study would be indicated to further explain how to encourage, within the medical setting, caregiver engagement in self-care activities.

Predictors of driving in individuals with relapsing-remitting multiple sclerosis.

BACKGROUND: We previously reported that performance on the Stroke Driver Screening Assessment (SDSA), a battery of four cognitive tests that takes less than 30 min to administer, predicted the driving performance of participants with multiple sclerosis (MS) on a road test with 86% accuracy, 80% sensitivity, and 88% specificity. OBJECTIVES: In this study, we further investigated if the addition of driving-related physical and visual tests and other previously identified cognitive predictors, including performance on the Useful Field of View test, will result in a better accuracy of predicting participants' on-road driving performance. METHODS: Forty-four individuals with relapsing-remitting MS (age = 46 ± 11 years, 37 females) and Expanded Disability Status Scale values between 1 and 7 were administered selected physical, visual and cognitive tests including the SDSA. The model that explained the highest variance of participants' performance on a standardized road test was identified using multiple regression analysis. A discriminant equation containing the tests included in the best model was used to predict pass or fail performance on the test. RESULTS: Performance on 12 cognitive and three visual tests were significantly associated with performance on the road test. Five of the tests together explained 59% of the variance and predicted the pass or fail outcome of the road test with 91% accuracy, 70% sensitivity, and 97% specificity. CONCLUSION: Participants' on-road performance was more accurately predicted by the model identified in this study than using only performance on the SDSA test battery. The five psychometric/off-road tests should be used as a screening battery, after which a follow-up road test should be conducted to finally decide the fitness to drive of individuals with relapsing-remitting MS. Future studies are needed to confirm and validate the findings in this study.

Myosin16b: The COOH-tail region directs localization to the nucleus and overexpression delays S-phase progression.

Rat Myo16a and Myo16b comprise the founding members of class XVI myosin and are characterized by an N-terminal ankyrin repeat domain thought to mediate an association with protein phosphatase 1 catalytic subunits 1alpha and 1gamma. Myo16b is the principal isoform and reveals predominant expression in developing neural tissue. Here, we use COS-7 cells as a model system to develop an understanding of Myo16b function. We find that Myo16b displays predominant localization in the nucleus of cells transitioning through interphase, but is not associated with processes of mitosis. Using a panel of EGFP-Myo16b-expression plasmids in transient transfection studies, we identified the COOH-terminal residues 1616-1912 as necessary and solely sufficient to target Myo16b to the nucleus. We show that the Myo16b-tail region directs localization to a nuclear compartment containing profilin and polymerized actin, which appears to form a three-dimensional meshwork through the depth of the nucleus. Further, we demonstrate that this compartment localizes within euchromatic regions of the genome and contains proliferating cell nuclear antigen (PCNA) and cyclin A, both markers of S-phase of the cell cycle. Cells transiently expressing Myo16b or Myo16b-tail region show limited incorporation of BrdU, delayed progression through S-phase of the cell cycle, and curtailed cellular proliferation.