Efficacy and safety of travoprost 0.004%/timolol 0.5% fixed combination as transition therapy in patients previously on prostaglandin analog monotherapy

Purpose: To assess the safety and efficacy of transitioning patients whose intraocular pressure (IOP) had been insufficiently controlled on prostaglandin analog (PGA) monotherapy to treatment with travoprost 0.004%/timolol 0.5% fixed combination with benzalkonium chloride (TTFC). Methods: This prospective, multicenter, open-label, historical controlled, single-arm study transitioned patients who had primary open-angle glaucoma, pigment dispersion glaucoma, or ocular hypertension and who required further IOP reduction from PGA monotherapy to oncedaily treatment with TTFC for 12 weeks. IOP and safety (adverse events, corrected distance visual acuity, and slit-lamp biomicroscopy) were assessed at baseline, week 4, and week 12. A solicited ocular symptom survey was administered at baseline and at week 12. Patients and investigators reported their medication preference at week 12. Results: Of 65 patients enrolled, 43 had received prior travoprost therapy and 22 had received prior nontravoprost therapy (n = 18, bimatoprost; n = 4, latanoprost). In the total population, mean IOP was significantly reduced from baseline (P = 0.000009), showing a 16.8% reduction after 12 weeks of TTFC therapy. In the study subgroups, mean IOP was significantly reduced from baseline to week 12 (P = 0.0001) in the prior travoprost cohort (19.0% reduction) and in the prior nontravoprost cohort (13.1% reduction). Seven mild, ocular, treatment-related adverse events were reported. Of the ten ocular symptom questions, eight had numerically lower percentages with TTFC compared with prior PGA monotherapy and two had numerically higher percentages with TTFC (dry eye symptoms and ocular stinging/burning). At week 12, TTFC was preferred over prior therapy for 84.2% of patients (48 of 57) by the patients themselves, and for 94.7% of patients (54 of 57) by their physicians. Conclusion: When TTFC replaced PGA monotherapy in patients whose IOP had been uncontrolled, the outcome was a significant reduction in IOP and an acceptable safety and tolerability profile. Most patients and investigators preferred TTFC to prior PGA monotherapy. © 2012 Costa et al, publisher and licensee Dove Medical Press Ltd.

Chemotaxonomic significance of 5-deoxyproanthocyanidins in Stryphnodendron species

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

5-HT2 and 5-HT3 receptors in the lateral parabrachial nucleus mediate opposite effects on sodium intake

The present study investigated the role of several 5-HT receptor subtypes in the lateral parabrachial nucleus (LPBN) in the control of sodium appetite (i.e. NaCl consumption). Male Holtzman rats had cannulas implanted bilaterally into the LPBN for the injection of 5-HT receptor agonists and antagonists in conjunction with either acute fluid depletion or 24-h sodium depletion. Following these treatments, access to 0.3 M NaCl was provided and the intakes of saline and water were measured for the next 2 h. Bilateral injections of the 5-HT2A receptor antagonist, ketanserin or the 5-HT2C receptor antagonist, mianserin into the LPBN increased 0.3 M NaCl intake without affecting water intake induced by acute fluid-depletion. Bilateral injections of the 5-HT2B receptor agonist, BW723C86 hydrochloride, had no effect on 0.3 M NaCl or water intake under these conditions. Treatment of the LPBN with the 5-HT2B/2C receptor agonist, 2-(2-methyl-4-clorophenoxy) propanoic acid (mCPP) caused dose-related reductions in 0.3 M NaCl intake after 24 h sodium depletion. The effects of mCPP were prevented by pretreating the LPBN with the 5-HT2B/2C receptor antagonist, SDZSER082. Activation of 5-HT3 receptors by the receptor agonist, 1-phenylbiguanicle (PBG) caused dose-related increases in 0.3 M NaCl intake. Pretreatment of the LPBN with the 5-HT3 receptor antagonist, 1-methyl-N-[8-methyl-8-azabicyclo (3.2.1)-oct-3-yl]-1H-indazole-3-carboxamide (LY-278,584) abolished the effects of PBG, but LY-278,584 had no effects on sodium or water intake when injected by itself. PBG injected into the LPBN did not alter intake of palatable 0.06 M sucrose in fluid replete rats. The results suggest that activation of the 5-HT2A and 5-HT2C receptor subtypes inhibits sodium ingestion. In contrast, activation of the 5-HT3 receptor subtype increases sodium ingestion. Therefore, multiple serotonergic receptor subtypes in the LPBN are implicated in the control of sodium intake, sometimes by mediating opposite effects of 5-HT. The results provide new information concerning the control of sodium intake by LPBN mechanisms. (C) 2007 IBRO. Published by Elsevier Ltd. All rights reserved.

Effects of travoprost 0.004% compared with latanoprost 0.005% on the intraocular pressure of normal dogs

Purpose To compare the effects of travoprost 0.004% and latanoprost 0.005% on the intraocular pressure (IOP) of normal dogs.Methods Twenty mixed breed dogs were randomized to two groups: latanoprost was used in group A and travoprost in group B. The drugs were instilled in the right eye of the dogs, whereas the left eye received placebo. Both drugs were instilled once a day at 8 AM during 5 days. IOP measurements were made at 8 AM, 10 AM, 2 PM and 8 PM during the 5 days of treatment, the 3 days that preceded treatment, and 3 days following treatment. Presence of blepharospasm, miosis, anterior chamber flare, and conjunctival hyperemia were evaluated during the study.Results Mean IOP was significantly reduced in the eyes treated with both latanoprost and travoprost, when compared with the eyes treated with placebo (P < 0.05). There was no statistically significant difference between the mean IOPs of eyes treated with latanoprost and travoprost at all time intervals during baseline, treatment, and recovery (P > 0.05). on the fifth day of treatment and on the first day of the recovery period, a severe ocular hypotension was noted with both drugs, resulting in imprecise readings with the tonometer. Miosis and conjunctival hyperemia were observed in the treated eyes of both groups, whereas flare was noticed in one latanoprost-treated eye.Conclusion Travoprost 0.004% significantly reduces the IOP in normal dogs. The hypotensive effect obtained with travoprost 0.004% is comparable to that obtained with latanoprost 0.005%.

Bull semen varibles after experimental exposure with Bovine Herpesvirus type 5

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of initial loading doses of 5 mg and 10 mg for warfarin therapy

CONTEXTO:A melhor dose para o início do tratamento anticoagulante com varfarina vem sendo debatida nos últimos dez anos. Em nosso meio, não observamos nenhum estudo comparativo quanto a estas características.OBJETIVO:Comparar segurança e eficácia de dois esquemas de dosagem inicial de varfarina para tratamento anticoagulante.MÉTODOS:Foram estudados prospectivamente 110 pacientes de ambos os sexos, consecutivos, com indicação de anticoagulação por tromboembolismo venoso ou arterial. Durante os três primeiros dias de tratamento, estes pacientes receberam doses adequadas de heparina (RT - razão dos tempos - alvo entre 1,5 e 2,5) e 5 mg de varfarina, cuja dose foi reajustada a partir do quarto dia pelo Razão Normatizada Internacional - RNI (alvo entre 2 e 3). Esse grupo foi comparado com série histórica de 110 pacientes que receberam 10 mg nos dois primeiros dias, 5 mg a partir do terceiro dia, com ajuste posterior de dose baseado no RNI. Os desfechos foram: recorrência do tromboembolismo, sangramentos e tempo para alcançar níveis terapêuticos.RESULTADOS:A eficácia, a segurança e o tempo de internação foram similares entre os grupos. O grupo que recebeu 10 mg atingiu níveis terapêuticos mais precocemente (média de 4,5 dias × 5,8 dias), sendo as doses na alta menores e os níveis terapêuticos mais adequados na primeira visita de retorno.CONCLUSÃO:O esquema de dosagem de 10 mg proporcionou menor tempo para alcançar nível terapêutico, com menores doses de varfarina na alta e RNI mais adequado no retorno.

Acaricidal effects of fluazuron (2.5 mg/kg) and a combination of fluazuron (1.6 mg/kg) + ivermectin (0.63 mg/kg), administered at different routes, against Rhipicephalus (Boophilus) microplus parasitizing cattle

The present study aimed to evaluate the acaricidal efficacy of fluazuron (2.5 mg/kg), administered as a pour-on, in comparison to an injectable formulation containing fluazuron (1.6 mg/kg) + ivermectin (0.63 mg/kg), against Rhipicephalus (Boophilus) microplus in naturally and experimentally infested cattle. Two studies were conducted with different tick strains, one with artificial infestations (Stall Test, using leight animals per group) and one with natural infestations (utilizing ten animals per group): In both studies, the animals were randomized, according to average tick counts performed on days -3, -2 and -1, into four groups: T01, negative control (saline solution); T02, pour-on fluazuron (2.5 mg/kg); T03: subcutaneous fluazuron (1.6 mg/kg) + ivermectin (0.63 mg/kg); and T04 subcutaneous ivermectin (0.63 mg/kg). Based on obtained results, and considering the utilized tick strains, it was possible to conclude that the pour-on fluazuron (2.5 mg/kg) formulation demonstrated high acaricidal efficacy, with protection periods ranging from 49 to 77 days against Rhipicephalus (Boophilus) microplus. On the other hand, for the injectable fluazuron (1.6 mg/kg) + ivermectin (0.63 mg/kg) formulation, it was not possible to observe elevated anti-R. (B.) microplus effect on both artificial and experimental infestation studies. Results observed for this combination were similar or inferior to those obtained by subcutaneous ivermectin (0.63 mg/kg). Future studies with this formulation containing fluazuron (1.6 mg/kg) + ivermectin (0.63 mg/kg), regarding pharmacokinetic and/or bioavailability profiles, or even studies analyzing both this active principles separately, are needed, seeking to better understand the effects of such combination against Rhipicephalus (Boophilus) microplus parasitizing cattle. (C) 2015 Elsevier Inc. All rights reserved.