Factors influencing the relationship between the dose of amlodipine required for blood pressure control and change in blood pressure in hypertensive cats

BACKGROUND: Hypertension is a common problem in elderly cats. In most cats, systolic blood pressure (SBP) of <160 mmHg is achieved in response to amlodipine besylate at either 0.625 or 1.25 mg q24h. The individual cat factors determining dose requirement dose have not been explored. AIMS: To determine whether individual cat factors influence the dose of amlodipine required to achieve adequate blood pressure control and to determine whether factors other than the prescribed dose of drug alter the achieved plasma amlodipine concentrations. METHODS: Fifty‐nine hypertensive cats that required 0.625 mg (A) and 41 cats that required 1.25 mg (B) amlodipine to reach a target SBP of <160 mmHg were identified, and plasma amlodipine concentrations were determined. Comparisons were made between groups, and multivariable linear regression models were performed to investigate predictors of antihypertensive response. RESULTS: Cats that required a greater dose of amlodipine had significantly higher SBP at diagnosis of hypertension (A: (median [25th, 75th percentile]) 182 [175,192] mmHg; B: 207 [194,217] mmHg, P < .001), but comparable blood pressure was achieved after treatment. Plasma amlodipine concentrations were directly related to the dose of amlodipine administered. At diagnosis, cats in group B had significantly lower plasma potassium concentration (A: 4.1 [3.8,4.5]; B: 3.8 [3.6,4.2] mEq/L, P < .01). Weight did not differ between groups. The decrease in SBP was directly and independently associated with the SBP at diagnosis and the plasma amlodipine concentration. CONCLUSIONS AND CLINICAL IMPORTANCE: Cats with higher blood pressure at diagnosis might require a greater dose of amlodipine to control their blood pressure adequately. Differences in amlodipine pharmacokinetics between cats do not seem to play a role in the antihypertensive response

Effect of Cyclooxygenase(COX)-1 and COX-2 inhibition on furosemide-induced renal responses and isoform immunolocalization in the healthy cat kidney

BACKGROUND: The role of cyclooxygenase(COX)-1 and COX-2 in the saluretic and renin-angiotensin responses to loop diuretics in the cat is unknown. We propose in vivo characterisation of isoform roles in a furosemide model by administering non-steroidal anti-inflammatory drugs (NSAIDs) with differing selectivity profiles: robenacoxib (COX-2 selective) and ketoprofen (COX-1 selective). RESULTS: In this four period crossover study, we compared the effect of four treatments: placebo, robenacoxib once or twice daily and ketoprofen once daily concomitantly with furosemide in seven healthy cats. For each period, urine and blood samples were collected at baseline and within 48 h of treatment starting. Plasma renin activity (PRA), plasma and urinary aldosterone concentrations, glomerular filtration rate (GFR) and 24 h urinary volumes, electrolytes and eicosanoids (PGE(2), 6-keto-PGF1(α,) TxB(2)), renal injury biomarker excretions [N-acetyl-beta-D-glucosaminidase (NAG) and Gamma-Glutamyltransferase] were measured. Urine volume (24 h) and urinary sodium, chloride and calcium excretions increased from baseline with all treatments. Plasma creatinine increased with all treatments except placebo, whereas GFR was significantly decreased from baseline only with ketoprofen. PRA increased significantly with placebo and once daily robenacoxib and the increase was significantly higher with placebo compared to ketoprofen (10.5 ± 4.4 vs 4.9 ± 5.0 ng ml(−1) h(−1)). Urinary aldosterone excretion increased with all treatments but this increase was inhibited by 75 % with ketoprofen and 65 % with once daily robenacoxib compared to placebo. Urinary PGE(2) excretion decreased with all treatments and excretion was significantly lower with ketoprofen compared to placebo. Urinary TxB(2) excretion was significantly increased from baseline only with placebo. NAG increased from baseline with all treatments. Immunohistochemistry on post-mortem renal specimens, obtained from a different group of cats that died naturally of non-renal causes, suggested constitutive COX-1 and COX-2 co-localization in many renal structures including the macula densa (MD). CONCLUSIONS: These data suggest that both COX-1 and COX-2 could generate the signal from the MD to the renin secreting cells in cats exposed to furosemide. Co-localization of COX isoenzymes in MD cells supports the functional data reported here. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s12917-015-0598-z) contains supplementary material, which is available to authorized users

Perceptions of Social Mobility: Development of a New Psychosocial Indicator Associated with Adolescent Risk Behaviors

Social class gradients have been explored in adults and children, but not extensively during adolescence. The first objective of this study was to examine the association between adolescent risk behaviors and a new indicator of adolescent relative social position, adolescent “perceived social mobility.” Second, it investigated potential underlying demographic, socioeconomic, and psychosocial determinants of this indicator. Data were taken from the 2004 urban adolescent module of Oportunidades, a cross-sectional study of Mexican adolescents living in poverty. Perceived social mobility was calculated for each subject by taking the difference between their rankings on two 10-rung ladder scales that measured (1) projected future social status and (2) current subjective social status within Mexican society. Adolescents with higher perceived social mobility were significantly less likely to report alcohol consumption, drinking with repercussions, compensated sex, police detainment, physical fighting, consumption of junk food or soda, or watching ≥4 h of television during the last viewing. They were significantly more likely to report exercising during the past week and using a condom during last sexual intercourse. These associations remained significant with the inclusion of covariates, including parental education and household expenditures. Multiple logistic regression analyses show higher perceived social mobility to be associated with staying in school longer and having higher perceived control. The present study provides evidence for the usefulness of perceived social mobility as an indicator for understanding the social gradient in health during adolescence. This research suggests the possibility of implementing policies and interventions that provide adolescents with real reasons to be hopeful about their trajectories

Control over phase separation and nucleation using a laser-tweezing potential

Control over the nucleation of new phases is highly desirable but elusive. Even though there is a long history of crystallization engineering by varying physicochemical parameters, controlling which polymorph crystallizes or whether a molecule crystallizes or forms an amorphous precipitate is still a poorly understood practice. Although there are now numerous examples of control using laser-induced nucleation, the absence of physical understanding is preventing progress. Here we show that the proximity of a liquid–liquid critical point or the corresponding binodal line can be used by a laser-tweezing potential to induce concentration gradients. A simple theoretical model shows that the stored electromagnetic energy of the laser beam produces a free-energy potential that forces phase separation or triggers the nucleation of a new phase. Experiments in a liquid mixture using a low-power laser diode confirm the effect. Phase separation and nucleation using a laser-tweezing potential explains the physics behind non-photochemical laser-induced nucleation and suggests new ways of manipulating matter

Weak localization effect on thermomagnetic phenomena

The quantum transport equation (QTE) is extended to study weak localization (WL) effects on galvanomagnetic and thermomagnetic phenomena. QTE has many advantages over the linear response method (LRM): (i) particle-hole asymmetry which is necessary for the Hall effect is taken into account by the nonequilibrium distribution function, while LRM requires expansion near the Fermi surface, (ii) when calculating response to the temperature gradient, the problem of WL correction to the heat current operator is avoided, (iii) magnetic field is directly introduced to QTE, while the LRM deals with the vector potential and and special attention should be paid to maintain gauge invariance, e.g. when calculating the Nernst effect the heat current operator should be modified to include the external magnetic field. We reproduce in a very compact form known results for the conductivity, the Hall and the thermoelectric effects and then we study our main problem, WL correction to the Nernst coefficient (transverse thermopower).Comment: 20 pages 2 figure

Phonon drag thermopower and weak localization

Previous experimental work on a two-dimensional (2D) electron gas in a Si-on-sapphire device led to the conclusion that both conductivity and phonon drag thermopower $S^g$ are affected to the same relative extent by weak localization. The present paper presents further experimental and theoretical results on these transport coefficients for two very low mobility 2D electron gases in $\delta-$doped GaAs/Ga$_x$Al$_{1-x}$As quantum wells. The experiments were carried out in the temperature range 3-7K where phonon drag dominates the thermopower and, contrary to the previous work, the changes observed in the thermopower due to weak localization were found to be an order of magnitude less than those in the conductivity. A theoretical framework for phonon drag thermopower in 2D and 3D semiconductors is presented which accounts for this insensitivity of $S^g$ to weak localization. It also provides transparent physical explanations of many previous experimental and theoretical results.Comment: 19 page Revtex file, 3 Postscript figur

Programming language specification and implementation

The specification of a programming language is a special case of the specification of software in general. This paper discusses the relation between semantics and implementation, or specification and program, using two very different languages for illustration. First, we consider small fragments of a specification of preliminary Ada, and show that what was considered a specification in VDM in 1980 now looks much like an implementation in a functional language. Also, we discuss how a formal specification may be valuable even though seen from a purely formal point of view it is flawed. Second, we consider the simple language of spreadsheet formulas and give a complete specification. We show that nondeterminism in the specification may reflect run-time nondeterminism, but also underspecification, that is, implementation-time design choices. Although specification nondeterminism may appear at different binding-times there is no conventional way to distinguish these. We also consider a cost semantics and find that the specification may need to contain some “artificial” nondeterminism for underspecification

Characterisation of feline renal cortical fibroblast cultures and their transcriptional response to transforming growth factor beta 1

Chronic kidney disease (CKD) is common in geriatric cats, and the most prevalent pathology is chronic tubulointerstitial inflammation and fibrosis. The cell type predominantly responsible for the production of extra-cellular matrix in renal fibrosis is the myofibroblast, and fibroblast to myofibroblast differentiation is probably a crucial event. The cytokine TGF-β1 is reportedly the most important regulator of myofibroblastic differentiation in other species. The aim of this study was to isolate and characterise renal fibroblasts from cadaverous kidney tissue of cats with and without CKD, and to investigate the transcriptional response to TGF-β1

Flattening of Single-Particle Spectra in Strongly Correlated Electron Systems and the Violation of the Wiedemann-Franz Law

The renormalization of the Wiedemann-Franz (WF) ratio in strongly correlated electron systems is analyzed within the Landau quasiparticle picture. We demonstrate that the WF law is violated: (i) at the quantum critical point, where the effective mass diverges, and (ii) beyond a point of fermion condensation, where the single-particle spectrum $\epsilon(p)$ becomes flat. Results of the analysis are compared with available experimental data.Comment: 6 pages, 5 figures, added reference