Novel inclusion complex of ibuprofen tromethamine with cyclodextrins: Physico-chemical characterization

Guest-host interactions of ibuprofen tromethamine salt (Ibu.T) with native and modified cyclodextrins (CyDs) have been investigated using several techniques, namely phase solubility diagrams (PSDs), proton nuclear magnetic resonance (H-1 NMR), differential scanning calorimetry (DSC), Fourier transform infrared spectroscopy (FT-IR), X-ray powder diffractometry (XRPD). scanning-electron microscopy (SEM) and molecular mechanics (MM). From the analysis of PSD data (A(L)-type) it is concluded that the anionic tromethamine salt of ibuprofen (pK(a) = 4.55) forms 1: 1 soluble complexes with all CyDs investigated in buffered water at pH 7.0, while the neutral form of Ibu forms an insoluble complex with beta-CyD (B-S-type) in buffered water at pH 2.0. Ibu.T has a lower tendency to complex with beta-CyD (K-11 = 58 M-1 at pH 7.0) compared with the neutral Ibu (K-11 = 4200 M (1)) in water. Complex formation of Ibu.T with beta-CyD (Delta G degrees = -20.4 kJ/mol) is enthalpy driven (Delta H degrees = -22.9 kJ/mol) and is accompanied by a small unfavorable entropy (Delta S degrees = -8.4 J/mol K) change. H-1 NMR studies and MM computations revealed that, on complexation, the hydrophobic central benzene ring of lbu.T and part of the isobutyl group reside within the beta-CyD cavity leaving the peripheral groups (carboxylate, tromethamine and methyl groups) located near the hydroxyl group networks at either rim of beta-CyD. PSD, H-1 NMR, DSC, FT-IR, XRPD, SEM and MM studies confirmed the formation of Ibu.T/beta-CyD inclusion complex in solution and the solid state. (C) 2009 Elsevier B.V. All rights reserved.

Reproductive performance of prepubertal Bos indicus heifers after progesterone-based treatments

The objective was to evaluate the effects of exogenous progesterone (P4) on reproductive performance of prepubertal Bos indicus heifers. Prepubertal Nelore heifers (n = 589; 24.0 +/- 1.13 mo; 298.0 +/- 1.89 kg; body condition score of 3.2 +/- 0.26; mean +/- SEM) were randomly assigned to receive, between experimental Days -12 and 0: no treatments (CIDR0; n = 113); a new intravaginal insert (CIDR) containing 1.9 g of P4 (CIDR1; n = 237); or a similar insert previously used three times, with each use occurring for 9 d (CIDR4; n = 239). An additional treatment group was pubertal heifers given 12.5 mg dinoprost tromethamine im on Day 0 (PGF; n = 346), and used as controls for evaluation of conception rates. on Day 0, transrectal palpation was done for uterine score evaluation (UtS; 1-3 scale), blood samples were taken for serum P4 concentrations, and follicle diameter (FD) was measured. The breeding season started on Day 1 and consisted of AI after detection of estrus between Days I and 45, and exposure to bulls between Days 46 and 90. There were effects of treatment (P < 0.05) on serum concentrations of P4 on Day 0 (0.37 +/- 0.16, 2.31 +/- 0.11, and 1.20 +/- 0.11 ng/mL for CIDR0, CIDR1, and CIDR4, respectively; mean SEM), FD on Day 0(9.45 +/- 0.24, 9.72 +/- 0.17, and 11.42 +/- 0.16 mm), UtS on Day 0 (1.49 +/- 0.06, 1.88 +/- 0.04, and 2.24 +/- 0.04), estrus detection rates at 7 d (19.5, 42.6, and 38.3%) and 45 d (52.2, 72.1, and 75.3%) of the breeding season, and on pregnancy rates at 7 d (5.3, 14.3, and 18.4%), 45 d (27.4, 39.2, and 47.7%) and 90 d (72.6, 83.5, and 83.7%) of the breeding season. Conception rate 7 d after the start of the breeding season was greater (P < 0.05) in heifers from the CIDR4 (46.8%) and PGF (43.8%) groups than in the CIDR0 (27.3%) and CIDR1 (33.7%) groups. In conclusion, exogenous P4 hastened puberty and improved pregnancy rates at the beginning of the breeding season in prepubertal Bos indicus heifers. Furthermore, previously used CIDR inserts were better than new inserts. (C) 2010 Elsevier B.V. All rights reserved.

Fixed-time artificial insemination with estradiol and progesterone for Bos indicus cows I: Basis for development of protocols

Five experiments were conducted on commercial farms in Brazil aiming to develop a fixed-time artificial insemination (TAI) protocol that achieved pregnancy rates between 40% and 55% in Bos indicus cows. These studies resulted in the development of the following protocol: insertion of all intravaginal device containing 1.9 g of progesterone (CIDR) plus 2.0 mg im estradiol benzoate on Day 0; 12.5 mg im dinoprost tromethamine on Day 7 in cycling cows or oil Day 9 in anestrous cows; CIDR withdrawal plus 0.5 mg im estradiol cypionate plus temporary calf removal on Day 9; TAI (48 h after CIDR withdrawal) plus reuniting of calves with their dams on Day 11. Reduced dose of prostaglandin F(2 alpha) (PGF(2 alpha): 12.5 mg im dinoprost tromethamine) effectively caused luteolysis. In cycling cows, fertility was greater when the treatment with PGF(2 alpha) was administered on Day 7 than oil Day 9, but in anestrous cows, no effects of time of the PGF(2 alpha) treatment were found. Estradiol cypionate effectively replaced estradiol benzoate or gonadotropin-releasing hormone as the ovulatory stimulus, reducing labor and cost. In this protocol, CIDR inserts were successfully used four times (9 d each use) with no detrimental effects on fertility. (C) 2009 Elsevier B.V. All rights reserved.

INFLUENCIA DO ACRESCIMO DE MANITOL A SOLUCAO NUTRIENTE NO DESEMPENHO MECANICO E NO GRAU DE EDEMA MIOCARDICO DE CORACOES ISOLADOS DE RATOS

Purpose - To analyse the influence of mannitol added to Krebs-Henseleit (KH) solution on the myocardium edema and myocardial function. Methods - Isolated rat heart under isovolumetric contractions studied according to Langendorff's technique were perfused with KH solution at constant flow during 90 min. The coronary perfusion pressure, diastolic and systolic pressures were recorded at every 15 min. At the end of the experiment, myocardium water content was measured in hearts perfused with KH solution (group I, n = 9) and in hearts perfused with KH solution plus 8 mM mannitol (group II, n = 8). These results were compared to non-perfused control heart (n = 9). Results - Myocardial water content was statistically higher in group I (80.8 ± 1.3%) compared to group II (78.1 ± 0.7%) and control group (75.5 ± 0.5%). Systolic arterial pressure was statistically higher in group I (86.2 ± 11.5 mmHg) compared to group II (72.7 ± 21.1 mmHg). There was no difference in the diastolic pressure between the two groups. Coronary perfusion pressure (Pp) increased progressively during the experiment in both groups. However, Pp was lower in group II than in group I. Conclusion - Mannitol added to KH solution significantly attenuates the myocardium edema in the isolated perfused rat heart.

Microhardness and fluoride release of restorative materials in different storage media

This study evaluated the surface microhardness and fluoride release of 5 restorative materials - Ketac-Fil Plus, Vitremer, Fuji II LC, Freedom and Fluorofil - in two storage media: distilled/deionized water and a pH-cycling (pH 4.6). Twelve specimens of each material, were fabricated and the initial surface microhardness (ISM) was determined in a Shimadzu HMV-2000 microhardness tester (static load Knoop). The specimens were submitted to 6- or 18-h cycles in the tested media. The solutions were refreshed at the end of each cycle. All solutions were stored for further analysis. After 15-day storage, the final surface microhardness (FSM) and fluoride release were measured. Fluoride dose was measured with a fluoride-specific electrode (Orion 9609-BN) and digital ion analyzer (Orion 720 A). The variables ISM, FSM and fluoride release were analyzed statistically by analysis of variance and Tukey's test (p<0.05). There was significant difference in FSM between the storage media for Vitremer (pH 4.6 = 40.2 ± 1.5; water = 42.6 ± 1.4), Ketac-Fil Plus (pH 4.6 = 73.4 ± 2.7; water = 58.2 ± 1.3) and Fluorofil (pH 4.6 = 44.3 ± 1.8; water = 38.4 ± 1.0). Ketac-Fil Plus (9.9 ± 18.0) and Fluorofil (4.4 ± 1.3) presented higher fluoride release in water, whereas Vitremer (7.4 ± 7.1), Fuji II LC (5.7 ± 4.7) and Freedom (2.1 ± 1.7) had higher fluoride release at pH 4.6. Microhardness and fluoride release of the tested restorative materials varied according to the storage medium.

Micropartículas biodegradáveis para liberação prolongada intraocular de cetorolaco de trometamina obtidas po Spray Drying

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Imunomarcação da óxido nítrico sintase induzível e da metaloproteinase-9 em úlceras corneais químicas de coelhos (Oryctolagus cuniculus - Linnaeus, 1758), tratadas com cetorolaco de trometamina

Pós-graduação em Cirurgia Veterinária - FCAV

Efeitos do cetorolaco de trometamina 0,5%, sem conservante, sobre a resposta inflamatória, a sensibilidade e re-epitelização corneal em coelhos submetidos a ulceração química da córnea

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Incidência de perdas gestacionais e efeito da vacinação contra doenças da reprodução nas taxas de prenhez em vacas de corte submetidas à inseminação artificial em tempo fixo

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Efeito do dispositivo de progesterona adicional durante protocolo de IATF e TETF à base de E2/P4 na fertilidade de vacas em lactação com baixa P4

Pós-graduação em Zootecnia - FMVZ

Função renal após colecistectomia por laparoscopia e analgesia com tramadol e dipirona ou cetorolaco

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Resposta luteal à PGF2α (Dinoprost Trometamina) durante as fases de luteogênese e manutenção do corpo lúteo em éguas

Pós-graduação em Medicina Veterinária - FMVZ

Increasing length of an estradiol and progesterone timed artificial insemination protocol decreases pregnancy losses in lactating dairy cows

Our hypothesis was that increasing the length of an estradiol and progesterone (P4) timed artificial insemination (TAI) protocol would improve pregnancy per artificial insemination (P/AI). Lactating Holstein cows (n = 759) yielding 31 +/- 0.30 kg of milk/d with a detectable corpus luteum (CL) at d - 11 were randomly assigned to receive TAI (d 0) following 1 of 2 treatments: (8d) d - 10 controlled internal drug release (CIDR) and 2.0 mg of estradiol benzoate, d - 3 = PGF(2 alpha) (25 mg of dinoprost tromethamine), d - 2 = CIDR removal and 1.0 mg of estradiol cypionate, d 0 = TAI; or (9d) d - 11 = CIDR and estradiol benzoate, d -4 = PGF(2 alpha), d -2 CIDR removal and estradiol cypionate, d 0 TAI. Cows were considered to have their estrous cycle synchronized in response to the protocol by the absence of a CL at artificial insemination (d 0) and presence of a CL on d 7. Pregnancy diagnoses were performed on d 32 and 60. The ovulatory follicle diameter at TAI (d 0) did not differ between treatments (14.7 +/- 0.39 vs. 15.0 +/- 0.40 mm for 8 and 9 d, respectively). The 9d cows tended to have greater P4 concentrations on d 7 in synchronized cows (3.14 +/- 0.18 ng/mL) than the 8d cows (3.05 +/- 0.18 ng/mL). Although the P/AI at d 32 [45 (175/385) vs. 43.9% (166/374) for 8d and 9d, respectively] and 60 [38.1 (150/385) vs. 40.4% (154/374) for 8d and 9d, respectively] was not different, the 9d cows had lower pregnancy losses [7.6% (12/166)] than 8d cows [14.7% (25/175)]. The cows in the 9d program were more likely to be detected in estrus [72.0% (269/374)] compared with 8d cows [62% (240/385)]. Expression of estrus improved synchronization [97.4 (489/501) vs. 81% (202/248)], P4 concentrations at d 7 (3.22 +/- 0.16 vs. 2.77 +/- 0.17 ng/mL), P/AI at d 32 [51.2 (252/489) vs. 39.4% (81/202)], P/AI at d 60 [46.3 (230/489) vs. 31.1% (66/202)], and decreased pregnancy loss [9.3 (22/252) vs. 19.8% (15/81)] compared with cows that did not show estrus, respectively. Cows not detected in estrus with small (<11 mm) or large follicles (>17 mm) had greater pregnancy loss; however, in cows detected in estrus, no effect of follicle diameter on pregnancy loss was observed. In conclusion, increasing the length of the protocol for TAI increased the percentage of cows detected in estrus and decreased pregnancy loss.

Ketorolac eye drops reduce inflammation and delay re-epithelization in response to corneal alkali burn in rabbits, without affecting iNOS or MMP-9

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

Dynamics of follicular growth and progesterone concentrations in cyclic and anestrous suckling Nelore cows (Bos indicus) treated with progesterone, equine chorionic gonadotropin, or temporary calf removal

The objective of this study was to investigate the effects of eCG and temporary calf removal (TCR) associated with progesterone (P4) treatment on the dynamics of follicular growth, CL size, and P4 concentrations in cyclic (n ¼ 36) and anestrous (n ¼ 30) Nelore cows. Cyclic (C) and anestrous (A) cows were divided into three groups. The control group received 2 mg of estradiol benzoate via intramuscular (IM) injection and an intravaginal device containing 1.9 g of P4 on Day 0. On Day 8, the device was removed, and the animals received 12.5 mg of dinoprost tromethamine IM. After 24 hours, the animals received 1 mg of estradiol benzoate IM. In the eCG group, cows received the same treatment described for the control group but also received 400 UI of eCG at the time of device removal. In the TCR group, calves were separated from the cows for 56 hours after device removal. Ultrasound exams were performed every 24 hours after device removal until the time of ovulation and 12 days after ovulation to measure the size of the CL. On the same day as the CL measurement, blood was collected to determine the plasma P4 level. Statistical analyses were performed with a significance level of P ≤ 0.05. In cyclic cows, the presence of the CL at the beginning of protocol resulted in a smaller follicle diameter at the time of device removal (7.4 ± 0.3 mm in cows with CL vs. 8.9 ± 0.4 mm in cows without CL; P ¼ 0.03). All cows ovulated within 72 hours after device removal. Anestrous cows treated with eCG or TCR showed follicle diameter at fixed-timed artificial insemination (A-eCG 10.2 ± 0.3 and A-TCR 10.3 ± 0.5 mm) and follicular growth rate (A-eCG 1.5 ± 0.2 and A-TCR 1.3 ± 0.1 mm/day) similar to cyclic cows (C-eCG 11.0 ± 0.6 and C-TCR 12.0 ± 0.5 mm) and (C-eCG 1.4 ± 0.2 and C-TCR 1.6 ± 0.2 mm/day, respectively; P ≤ 0.05). Despite the similarities in CL size, the average P4 concentration was higher in the A-TCR (9.6 ± 1.4 ng/mL) than in the A-control (4.0 ± 1.0 ng/mL) and C-TCR (4.4 ± 1.0 ng/mL) groups (P < 0.05). From these results, we conclude that eCG treatment and TCR improved the fertility of anestrous cows by providing follicular growth rates and size of dominant follicles similar to cyclic cows. Additionally, TCR increases the plasma concentrations of P4 in anestrous cows