Pituitary Apoplexy After a Single Dose of Long-Acting Octreotide

Pituitary apoplexy (PA) is a rare and potentially life-threatening syndrome resulting from an acute infarction or hemorrhage of the pituitary gland. Although the pathogenesis is not fully understood, some predisposing factors such as pituitary stimulation tests, diabetes mellitus, anticoagulant or antiplatelet aggregation therapy, head trauma, and high blood pressure may play a role in its pathophysiology. Octreotide is the mainstay of medical treatment for acromegaly. The majority of reported complications of octreotide therapy are gastrointestinal. We report the case of a 51-year-old acromegalic woman who developed pituitary apoplexy within the context of high blood pressure and a single dose of long-acting octreotide. Our data suggest that the combination of hypertension and octreotide therapy enhances the risk of pituitary apoplexy.

Pharmacokinetics of a new long acting endectocide formulation containing 2.25% ivermectin and 1.25% abamectin in cattle

The objective of this study was to determine the kinetic parameters of a new formulation that contained 2.25% ivermectin combined with 1.25% abamectin in bovine plasma. The results for 2.25% ivermectin: C-max (37.11 ng/mL +/- 7.42), T-max (16 days +/- 5.29), T-1/2 (44.62 days +/- 53.89), AUC (928.2 ng.day/mL +/- 153.83) and MRT (36.73 days +/- 33.64), and for 1.25% abamectin: C-max (28.70 ng/mL +/- 9.54), T-max (14 days +/- 4.04), T-1/2 (15.40 days +/- 11.43), AUC (618.05 ng.day/mL +/- 80.27) and MRT (20.79 days +/- 8.43) suggest that this combination of 2.25% ivermectin + 1.25% abamectin possesses properties that give this pharmaceutical formula a longer activity time than two of the commercial products tested (1% ivermectin and 1% abamectin), and showed similarity to 3.15% ivermectin.

Corpus Luteum Development and Function after Supplementation of Long-Acting Progesterone During the Early Luteal Phase in Beef Cattle

Contents: Strategic supplementation of P4 may be used to increase conception rates in cattle, but timing of supplementation in relation to ovulation, mass of supplementary P4 and formulation of the P4-containing supplement has not been determined for beef cattle. Effects of supplementation of long-acting progesterone (P4) on Days 2 or 3 post-ovulation on development, function and regression of corpus luteum (CL) were studied in beef cattle. Cows were synchronized with an oestradiol/P4-based protocol and treated with 150 or 300 mg of long-acting P4 on Day 2 or 3 post-ovulation (6-7 cows/group). Colour-doppler ultrasound scanning and blood sample collection were performed from Day 2-21.5. Plasma P4 concentrations were greater (p < 0.05) from Day 2.5-5.5 in the Day 2-treated groups and from Day 3.5-5.5 in the Day 3-treated cows than in the control group. CL area and blood flow during Day 2-8.5 did not differ (p > 0.05) among groups, suggesting no effect of P4 treatment on luteal development. The frequency of cows that began luteolysis before Day 15 was greater (p < 0.04) in cows treated with 300 mg than in the controls, but there were no differences between non-treated and 150 mg-treated cows. The interval from pre-treatment ovulation to functional and structural luteolysis was shorter (p < 0.01) in the combined P4-treated groups than in the control cows. In conclusion, was showed for the first time that long-acting P4 supplementation on Day 2 or 3 post-ovulation increases P4 concentrations for ≥3 day, has no effect on luteal development, but anticipates the beginning of luteolysis in beef cattle. © 2013 Blackwell Verlag GmbH.

Medroxyprogesterone acetate or long-acting progesterone in the biostimulation of lambs

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Prolonged amelioration of acute lung allograft rejection by overexpression of human interleukin-10 under control of a long acting ubiquitin C promoter in rats

BACKGROUND: The prolonged effect of electroporation-mediated human interleukin-10 (hIL-10) overexpression in skeletal muscle under the control of the constitutional polyubiquitin C promoter (pUb hIL-10) on rat lung allograft rejection was evaluated. METHODS: Left lung allotransplantation was performed from Brown-Norway to Fischer-F344 rats. Either 2.5 mug pCIK hIL-10 (hIL-10/cytomegalovirus early promoter enhancer) alone (Group I/sacrifice Day 5 and II/sacrifice Day 10) or in combination with 2.5 mug pUb hIL-10 (hIL-10/UbC promoter; Group III/sacrifice Day 10) were injected into the tibialis anterior muscle of the recipient, followed by electroporation 24 hours before transplantation. Animals in Control Groups IV and V without gene transfer were euthanized on Day 5 and 10, respectively. All animals received a daily non-therapeutic dose of cyclosporine A (2.5 mg/kg). RESULTS: In Control Group IV, complete rejection (median A3B3) was noted on Day 5 with a Pao(2) of 43 +/- 9 mm Hg. In recipients of Control Group V, measurement of gas exchange on Day 10 and rejection grading was impossible because of complete destruction of the allograft. Group I animals on Day 5 (233 +/- 123 mm Hg; p = 0.02 vs Group IV) and Group II animals on Day 10 (150 +/- 139 mm Hg; p = 0.15 vs Group IV) demonstrated improved graft function. Graft function in Group III was further improved on Day 10 (299 +/- 123 mm Hg; p = 0.002 vs Group IV; p = 0.05 vs Group II; p = 0.36 vs Group I). Rejection was significantly reduced in Group III (median, A2B2) compared with Group II (median, A4B3; p < 0.05). CONCLUSIONS: Interleukin-10 overexpression under control of the constitutive ubiquitin C promoter ameliorates acute rejection and preserves lung graft function for a prolonged time.

Activities of ertapenem, a new long-acting carbapenem, against penicillin-sensitive or -resistant pneumococci in experimental meningitis

The penetration of ertapenem, a new carbapenem with a long half-life, reached 7.1 and 2.4% into inflamed and noninflamed meninges, respectively. Ertapenem had excellent antibacterial activity in the treatment of experimental meningitis due to penicillin-sensitive and -resistant pneumococci, leading to a decrease of 0.69 +/- 0.17 and 0.59 +/- 0.22 log(10) CFU/ml x h, respectively, in the viable cell counts in the cerebrospinal fluid. The efficacy of ertapenem was comparable to that of standard regimens (ceftriaxone monotherapy against the penicillin-sensitive strain and ceftriaxone combined with vancomycin against the penicillin-resistant strain). In vitro, ertapenem in concentrations above the MIC was highly bactericidal against both strains. Even against a penicillin- and quinolone-resistant mutant, ertapenem had similar bactericidal activity in vitro.

Narcotic antagonists, the search for long-acting preparations /

Mode of access: Internet.

Plasma concentrations of tafenoquine, a new long-acting antimalarial agent, in Thai soldiers receiving monthly prophylaxis

We measured plasma tafenoquine concentrations in Thai soldiers given a monthly regimen of tafenoquine to determine whether these concentrations adequately suppressed malarial infections on the Thai- Cambodian border. After receiving a treatment course of artesunate and doxycycline, 104 male soldiers were administered a loading dose of tafenoquine ( 400 mg daily for 3 days), followed by tafenoquine monthly ( 400 mg every 4 weeks) for 5 months. Consecutive monthly mean ( +/- standard deviation) trough plasma tafenoquine concentrations were 223 +/- 41, 127 +/- 29, 157 +/- 51. 120 +/- 24, and 88 +/- ng/ mL. Only 1 soldier developed malaria during the study. At the time of malaria diagnosis, his plasma tafenoquine concentration was 40 ng/ mL, which was similar to 3- fold lower than the trough concentrations of the other soldiers. Although low tafenoquine concentrations appear to be uncommon, additional investigations are needed to determine the relationship between plasma tafenoquine concentrations and suppression of malaria.

Efficacy and safety of second-generation antipsychotic long-acting injections (SGA LAIs) in maintenance treatment of bipolar disorder:protocol for a systematic review and meta-analysis

INTRODUCTION: Bipolar disorder requires long-term treatment but non-adherence is a common problem. Antipsychotic long-acting injections (LAIs) have been suggested to improve adherence but none are licensed in the UK for bipolar. However, the use of second-generation antipsychotics (SGA) LAIs in bipolar is not uncommon albeit there is a lack of systematic review in this area. This study aims to systematically review safety and efficacy of SGA LAIs in the maintenance treatment of bipolar disorder. METHODS AND ANALYSIS: The protocol is based on Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and will include only randomised controlled trials comparing SGA LAIs in bipolar. PubMed, EMBASE, CINAHL, Cochrane Library (CENTRAL), PsychINFO, LiLACS, http://www.clinicaltrials.gov will be searched, with no language restriction, from 2000 to January 2016 as first SGA LAIs came to the market after 2000. Manufacturers of SGA LAIs will also be contacted. Primary efficacy outcome is relapse rate or delayed time to relapse or reduction in hospitalisation and primary safety outcomes are drop-out rates, all-cause discontinuation and discontinuation due to adverse events. Qualitative reporting of evidence will be based on 21 items listed on standards for reporting qualitative research (SRQR) focusing on study quality (assessed using the Jadad score, allocation concealment and data analysis), risk of bias and effect size. Publication bias will be assessed using funnel plots. If sufficient data are available meta-analysis will be performed with primary effect size as relative risk presented with 95% CI. Sensitivity analysis, conditional on number of studies and sample size, will be carried out on manic versus depressive symptoms and monotherapy versus adjunctive therapy.

GIP(Lys16PAL) and GIP(LyS37PAL):novel long-acting acylated analogues of glucose-dependent insulinotropic polypeptide with improved antidiabetic potentia

Glucose-dependent insulinotropic polypeptide (GIP) is a physiological insulin releasing peptide. We have developed two novel fatty acid derivatized GIP analogues, which bind to serum albumin and demonstrate enhanced duration of action in vivo. GIP(Lys16PAL) and GIP(Lys37PAL) were resistant to dipeptidyl peptidase IV (DPP IV) degradation. In vitro studies demonstrated that GIP analogues retained their ability to activate the GIP receptor through production of cAMP and to stimulate insulin secretion. Intraperitoneal administration of GIP analogues to obese diabetic (ob/ob) mice significantly decreased the glycemic excursion and elicited increased and prolonged insulin responses compared to native GIP. A protracted glucose-lowering effect was observed 24 h following GIP(Lys37PAL) administration. Once a day injection for 14 days decreased nonfasting glucose, improved glucose tolerance, and enhanced the insulin response to glucose. These data demonstrate that fatty acid derivatized GIP peptides represent a novel class of long-acting stable GIP analogues for therapy of type 2 diabetes. © 2006 American Chemical Society.

Long-Acting b-Agonist in Combination or Separate Inhaler as Step-Up Therapy for Children with Uncontrolled Asthma Receiving Inhaled Corticosteroids

Acknowledgments The authors thank Prof. Stanley Szefler for his comments on the paper and Lisa Law for help with editing