Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach

Citation: Lin, Z. M., Cuneo, M., Rowe, J. D., Li, M. J., Tell, L. A., Allison, S., . . . Gehring, R. (2016). Estimation of tulathromycin depletion in plasma and milk after subcutaneous injection in lactating goats using a nonlinear mixed-effects pharmacokinetic modeling approach. Bmc Veterinary Research, 12, 10. https://doi.org/10.1186/s12917-016-0884-4Background: Extra-label use of tulathromycin in lactating goats is common and may cause violative residues in milk. The objective of this study was to develop a nonlinear mixed-effects pharmacokinetic (NLME-PK) model to estimate tulathromycin depletion in plasma and milk of lactating goats. Eight lactating goats received two subcutaneous injections of 2.5 mg/kg tulathromycin 7 days apart; blood and milk samples were analyzed for concentrations of tulathromycin and the common fragment of tulathromycin (i.e., the marker residue CP-60,300), respectively, using liquid chromatography mass spectrometry. Based on these new data and related literature data, a NLME-PK compartmental model with first-order absorption and elimination was used to model plasma concentrations and cumulative excreted amount in milk. Monte Carlo simulations with 100 replicates were performed to predict the time when the upper limit of the 95% confidence interval of milk concentrations was below the tolerance. Results: All animals were healthy throughout the study with normal appetite and milk production levels, and with mild-moderate injection-site reactions that diminished by the end of the study. The measured data showed that milk concentrations of the marker residue of tulathromycin were below the limit of detection (LOD = 1.8 ng/ml) 39 days after the second injection. A 2-compartment model with milk as an excretory compartment best described tulathromycin plasma and CP-60,300 milk pharmacokinetic data. The model-predicted data correlated with the measured data very well. The NLME-PK model estimated that tulathromycin plasma concentrations were below LOD (1.2 ng/ml) 43 days after a single injection, and 62 days after the second injection with a 95% confidence. These estimated times are much longer than the current meat withdrawal time recommendation of 18 days for tulathromycin in non-lactating cattle. Conclusions: The results suggest that twice subcutaneous injections of 2.5 mg/kg tulathromycin are a clinically safe extra-label alternative approach for treating pulmonary infections in lactating goats, but a prolonged withdrawal time of at least 39 days after the second injection should be considered to prevent violative residues in milk and any dairy goat being used for meat should have an extended meat withdrawal time

Awareness and perceptions of electroconvulsive therapy among psychiatric patients: a cross-sectional survey from teaching hospitals in Karachi, Pakistan

<p>Abstract</p> <p>Background</p> <p>Electroconvulsive therapy (ECT) is shown to be effective in many psychiatric illnesses, but its distorted projection by the Pakistani media and its unregulated use by many physicians across the country have adversely affected its acceptability. Given this situation we aimed to assess the awareness and perceptions regarding ECT as a treatment modality among the psychiatric patients.</p> <p>Methods</p> <p>This was a questionnaire based cross-sectional study carried out at 2 tertiary care hospitals in Karachi, Pakistan.</p> <p>Results</p> <p>We interviewed 190 patients of which 140 were aware of ECT. The study showed that the level of education had a significant impact on the awareness of ECT (p = 0.009). The most common source of awareness was electronic and print media (38%), followed by relatives (24%) and doctors (23%). Physical injuries (42%) and neurological (12%) and cognitive disturbances (11%) were the commonly feared side effects. The most popular belief about ECT was that it was a treatment of last resort (56%). Thirty-nine percent thought that ECT could lead to severe mental and physical illness and 37% considered it inhumane. Patients' willingness to receive ECT was dependant on whether or not they were convinced of its safety (p = 0.001) and efficacy (p = 0.0001).</p> <p>Conclusion</p> <p>We identified a serious lack of dissemination of information regarding ECT by the psychiatrists and the mental health care providers. This may be the result of an inadequate postgraduate training in Pakistan or just a lack of concern about the mentally ill patients. The media seemed to be the major source of information for our patients. We also saw the prevalence of a variety of myths regarding ECT in our society, which we feel may be responsible for the patients' adverse attitudes. Given the widespread applicability of ECT there is a dire need to dispel these misconceptions and improve its acceptability.</p

Copper induces Cu-ATPase ATP7A mRNA in a fish cell line, SAF1

Copper transporting ATPase, ATP7A, is an ATP dependent copper pump present in all vertebrates, critical for the maintenance of intracellular and whole body copper homeostasis. Effects of copper treatment on ATP7A gene expression in fibroblast cells (SAF1) of the sea bream (Sparus aurata) were investigated by qRT-PCR and by a medium density microarray from a closely related species, striped sea bream (Lithognathus mormyrus). To discriminate between the effects of Cu and other metals, SAF1 cells were exposed to sub-toxic levels of Cu, Zn and Cd. Expression of Cu homeostasis genes copper transporter 1 (CTR1), Cu ATPase (ATP7A), Cu chaperone (ATOX1) and metallothionein (MT) together with the oxidative stress markers glutathione reductase (GR) and Cu/Zn superoxide dismutase (CuZn/SOD) were measured 0, 4 and 24 hours post-exposure by qRT-PCR. Microarray was conducted on samples from 4 hours post Cu exposure. Cu, Zn and Cd increased MT and GR mRNA levels, while only Cu increased ATP7A mRNA levels. Microarray results confirmed the effects of Cu on ATP7A and MT and in addition showed changes in the expression of genes involved in protein transport and secretion. Results suggest that ATP7A may be regulated at the transcriptional level directly by Cu and by a mechanism that is different from that exerteted by metals on MT genes

Periodontal disease and some adverse perinatal outcomes in a cohort of low risk pregnant women

Objective: To evaluate the association of periodontal disease (PD) in pregnancy with some adverse perinatal outcomes. Method: This cohort study included 327 pregnant women divided in groups with or without PD. Indexes of plaque and gingival bleeding on probing, probing pocket depth, clinical attachment level and gingival recession were evaluated at one periodontal examination below 32 weeks of gestation. The rates of preterm birth (PTB), low birth weight (LBW), small for gestational age (SGA) neonates and prelabor rupture of membranes (PROM) were evaluated using Risk Ratios (95%CI) and Population Attributable Risk Fractions. Results: PD was associated with a higher risk of PTB (RRadj. 3.47 95% CI 1.62-7.43), LBW (RRadj. 2.93 95% CI 1.36-6.34) and PROM (RRadj. 2.48 95% CI 1.35-4.56), but not with SGA neonates (RR 2.38 95% CI 0.93 - 6.10). Conclusions: PD was a risk factor for PT, LBW and PROM among Brazilian low risk pregnant women

Campylobacter pinnipediorum subsp. caledonicus and C. pinnipediorum subsp. pinnipediorum recovered from abscesses in pinnipeds

Campylobacter pinnipediorum was described recently for isolates recovered from pinnipeds. The novel species was further split into 2 subspecies based on host and geography, with C. pinnipediorum subsp. pinnipediorum recovered from otariid seals in California (USA) and C. pinnipediorum subsp. caledonicus recovered from phocid seals in Scotland. We report details of the infections of 7 pinnipeds from which C. pinnipediorum was isolated: C. pinnipediorum subsp. caledonicus was isolated from 2 harbour seals Phoca vitulina and a single grey seal Halichoerus grypus, and C. pinnipediorum subsp. pinnipediorum was isolated from California sea lions Zalophus californianus. Six of the isolates were recovered from samples collected at post-mortem investigation. In 2 of the Scottish seals and in 3 of the California seals, C. pinnipediorum was the sole bacterial isolate recovered from abscesses present and suggests they may have resulted from conspecific or intraspecific bite wounds