Oxoisoaporphine nanocapsules for treating depression

Oxoisoaporphine nanocapsules for treating depression. Nanocapsule systems are described that incorporate compounds of formula I or II that allow controlled, timed release of said compounds. Also described are the production method, the pharmaceutical compositions and the use for preparing a drug.

Timing of prostaglandin F2α treatment in an estrogen-based protocol for timed artificial insemination or timed embryo transfer in lactating dairy cows

Objectives were to investigate progesterone concentrations and fertility comparing 2 different intervals from PGF2α treatment and induced ovulation in an estrogen-based ovulation synchronization protocol for timed artificial insemination (TAI) or timed embryo transfer (TET) in lactating dairy cows. A total of 1,058 lactating Holstein cows [primiparous (n=371) and multiparous (n=687)], yielding 34.1±0.33 kg of milk/d at various days in milk were randomly assigned to receive treatment with PGF2α on either d 7 or 8 of the following protocol: d 0: 2mg of estradiol benzoate + controlled internal drug release device; d 8: controlled internal drug release device removal + 1.0mg of estradiol cypionate; d 10: TAI or d 17: TET. Only cows with a corpus luteum at d 17 received an embryo and all cows received GnRH at TET. Pregnancy diagnoses were performed by detection (transrectal ultrasonography) of an embryo on d 28 or a fetus on d 60. Fertility [pregnancy per artificial insemination (P/AI) or pregnancy per embryo transfer (P/ET)] was affected by breeding technique (AI vs. ET) and time of PGF2α treatment (d 7 vs. 8) at the 28-d pregnancy diagnosis for TAI [32.9% (238) vs. 20.6% (168)] and TET cows [47% (243) vs. 40.7% (244)] and at the 60-d pregnancy diagnosis for TAI [30% (238) vs. 19.2% (168)] and TET cows [37.9% (243) vs. 33.5% (244)]. The progesterone (P4) concentration at d 10 altered fertility in TAI cows, with higher P/AI in cows with P4 concentration <0.1 ng/mL compared with cows with P4 concentration ≥0.1 ng/mL, and in ET cows, with higher P/ET in cows with P4 concentration <0.22 ng/mL compared with cows with P4 concentration ≥0.22 ng/mL. Prostaglandin F2α treatment at d 7 increased the percentage of cows with P4 <0.1 ng/mL on d 10 [39.4 (85) vs. 23.2 (54)]. Reducing the period between PGF2α and TAI from 72 to 48h in dairy cows resulted in a clear reduction in fertility in cows bred by TAI and a subtle negative effect in cows that received TET. The earlier PGF2α treatment benefits are most likely mediated through gamete transport, fertilization, or early embryo development and a more subtle effect of earlier PGF2α treatment that may be mediated through changes in the uterine or hormonal environment that manifests itself after ET on d 7. © 2013 American Dairy Science Association.

Timed artificial insemination programs during the summer in lactating dairy cows: Comparison of the 5-d Cosynch protocol with an estrogen/progesterone-based protocol

The objective of this study was to compare a GnRH-based to an estrogen/progesterone (E2/P4)-based protocol for estrous cycle synchronization and fixed timed artificial insemination (TAI), both designed for synchronization of ovulation and to reduce the period from follicular emergence until ovulation in cows with a synchronized follicular wave. A total of 1,190 lactating Holstein cows (primiparous: n = 685 and multiparous: n = 505) yielding 26.5 ± 0.30 kg of milk/d at 177 ± 5.02 d in milk were randomly assigned to receive one of the following programs: 5-d Cosynch protocol [d -8: controlled internal drug release (CIDR) + GnRH; d -3: CIDR removal + PGF2α; d -2: PGF2α; d 0: TAI + GnRH] or E2/P4 protocol (d -10: CIDR + estradiol benzoate; d -3: PGF2α; d -2: CIDR removal + estradiol cypionate; d 0: TAI). Rectal temperature and circulating progesterone (P4) were measured on d -3, -2, 0 (TAI), and 7. The estrous cycle was considered to be synchronized when P4 was ≥1.0 ng/mL on d 7 in cows that had luteolysis (P4 ≤0.4 ng/mL on d 0). To evaluate the effects of heat stress, cows were classified by number of heat stress events: 0, 1, and 2-or-more measurements of elevated body temperature (≥39.1°C). Pregnancy success (pregnancy per artificial insemination, P/AI) was determined at d 32 and 60 after TAI. The cows in the 5-d Cosynch protocol had increased circulating P4 at the time of PGF2α injection (2.66 ± 0.13 vs. 1.66 ± 0.13 ng/mL). The cows in the E2/P4 protocol were more likely to be detected in estrus (62.8 vs. 43.4%) compared with the cows in the 5-d Cosynch protocol, and expression of estrus improved P/AI in both treatments. The cows in the 5-d Cosynch protocol had greater percentage of synchronized estrous cycle (78.2%), compared with cows in the E2/P4 protocol (70.7%). On d 60, the E2/P4 protocol tended to improve P/AI (20.7 vs. 16.7%) and reduced pregnancy loss from 32 to 60 d (11.0 vs. 19.6%), compared with the 5-d Cosynch protocol. In cows with their estrous cycle synchronized, the E2/P4 protocol had greater P/AI (25.6 vs. 17.7%) on d 60 and lower pregnancy loss from 32 to 60 d (6.7 vs. 21.7%) compared with cows in the 5-d Cosynch protocol. Follicle diameter affected pregnancy loss from 32 to 60 d only in the cows in the 5-d Cosynch protocol, with smaller follicles resulting in greater pregnancy loss. Pregnancy per AI at d 60 was different between protocols in the cows with 2 or more measurements of heat stress (5-d Cosynch = 12.2% vs. E2/P4 = 22.8%), but not in the cows without or with 1 heat stress measurement. In conclusion, the 5-d Cosynch protocol apparently produced better estrous cycle synchronization than the E2/P4 protocol but did not improve P/AI. The potential explanation for these results is that increased E2 concentrations during the periovulatory period can improve pregnancy success and pregnancy maintenance, and this effect appears to be greatest in heat-stressed cows when circulating E2 may be reduced. © 2013 American Dairy Science Association.

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.

Effect of interval from induction of puberty to initiation of a timed AI protocol on pregnancy rate in Nellore heifers

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)

Effect of adding a gonadotropin-releasing-hormone treatment at the beginning and a second prostaglandin F-2 alpha treatment at the end of an estradiol-based protocol for timed artificial insemination in lactating dairy cows during cool or hot seasons of the year

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

A field study to describe diel, tidal and semilunar rhythms of larval release in an assemblage of tropical rocky shore crabs

Available information on the larval release rhythms of brachyurans is biased to temperate estuarine species and outcomes resulting from some sort of artificial manipulation of ovigerous females. In this study we applied field methods to describe the larval release rhythms of an assemblage of tropical rocky shore crabs. Sampling the broods of ovigerous females of Pachygrapsus transversus at two different shores indicated a spatially consistent semilunar pattern, with larval release maxima around the full and new moon. Yet, synchronism between populations varied considerably, with the pattern obtained at the site exposed to a lower wave action far more apparent. Breeding cohorts at one of the sampled shores apparently belonged to actual age groups composing the ovigerous population. The data suggest that these breeding groups release their larvae in alternate syzygy periods, responding to a lunar cycle instead of the semilunar pattern observed for the whole population. For the description of shorter-term rhythms, temporal series at hour intervals were obtained by sampling the plankton and confinement boxes where ovigerous females were held. Unexpectedly, diurnal release activity prevailed over nocturnal hatching. Yet, only grapsids living higher on the shore exhibited strong preferences over the diel cycle, with P. transversus releasing their larvae during the day and Geograpsus lividus during the night. The pea crab Dissodactylus crinitichelis, the spider crab Epialtus brasiliensis and a suite of xanthoids undertook considerable releasing activity in both periods. Apart from the commensal pea crab D. crinitichelis, all other taxa revealed tide-related rhythms of larval release, with average estimates of the time of maximum hatching always around the time of high tides; usually during the flooding and slack, rather than the ebbing tide. Data obtained for P. transversus females held in confinement boxes indicated that early larval release is mostly due to nocturnal hatching, while zoeal release in diurnal groups took place at the time of high tide. Since nocturnal high tides at the study area occurred late, sometimes close to dusk, early release would allow more time for offshore transport of larvae when the action of potential predators is reduced.

Effect of sequence of insemination after simultaneous thawing of multiple semen straws on conception rate to timed AI in suckled multiparous Nelore cows

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Assessment of field fertility and several in vitro sperm characteristics following the use of different Angus sires in a timed-AI program with suckled Nelore cows

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

On the release of metronidazole from natural rubber latex membranes

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

Nitric oxide release using natural rubber latex as matrix

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

Inclusion complex of piroxicam with beta-cyclodextrin and incorporation in cationic microemulsion. In vitro drug release and in vivo topical anti-inflammatory effect

Topical formulations of piroxicam were evaluated by determination of their in vitro release and in vivo anti-inflammatory effect. The in vitro release assay demonstrated that the microemulsion (ME) systems provided a reservoir effect for piroxicam release. However, the incorporation of the ME into carboxyvinilic gel provoked a greater reduction in the release of piroxicam than the ME system alone. Anti-inflammatory activity was carried out by the cotton pellet granuloma inhibition bioassay. Topical anti-inflammatory effect of the piroxicam inclusion complex/ME contained in carboxyvinilic gel showed significant inhibition of the inflammation process (36.9%, P < 0.05). Subcutaneous administration of the drug formulations showed a significant effect on the inhibition of inflammation, 68.8 and 70.5%, P <0.05, when the piroxicam was incorporated in ME and in the combined system beta -cyclodextrin (B-CD)/ME, respectively, relative to the buffered piroxicam (42.2%). These results demonstrated that the ME induced prolonged effects, providing inhibition of the inflammation for 9 days after a single dose administration. (C) 2001 Elsevier B.V. B.V. All rights reserved.

Semisolid systems containing propolis for the treatment of periodontal disease: In vitro release kinetics, syringeability, rheological, textural, and mucoadhesive properties

Formulations containing poloxamer 407 (P407), carbopol 934P (C934P), and propolis extract (PE) were designed for the treatment of periodontal disease. Gelation temperature, in vitro drug release, rheology, hardness, compressibility, adhesiveness, mucoadhesion, and syringeability of formulations were determined. Propolis release from formulations was controlled by the phenomenon of relaxation of polymer chains. Formulations exhibited pseudoplastic flow and low degrees of thixotropy or rheopexy. In most samples, increasing the concentration of C934P content significantly increased storage modulus (G'), loss modulus (G ''), and dynamic viscosity (n') at 5 degrees C, G '' exceeded G'. At 25 and 37 degrees C, n' of each formulation depended on the oscillatory frequency. Formulations showed thermoresponsive behavior, existing as a liquid at room temperature and gel at 34-37 degrees C. Increasing the C934P content or temperature significantly increased formulation hardness, compressibility, and adhesiveness. The greatest mucoadhesion was noted in the formulation containing 15% P407 (w/w) and 0.25% C934P (w/w). The work of syringeability values of all formulations were similar and very desirable with regard to ease of administration. The data obtained in these formulations indicate a potentially useful role in the treatment of periodontitis and suggest they are worthy of clinical evaluation. (c) 2007 Wiley-Liss, Inc.

Preparation and characterisation of Dextran-70 hydrogel for controlled release of praziquantel

Um hidrogel foi desenvolvido a partir de dextrano 70 kDa (DEX-70) e praziquantel incorporado (PZQ) como fármaco modelo. Propriedades biofarmacêuticas, como solubilidade e velocidade de dissolução, foram analisadas no desenvolvimento do hidrogel. Além disso, o hidrogel também foi caracterizado por espectroscopia na região do infravermelho e calorimetria diferencial exploratória (DSC). Testes da taxa de intumescimento mostraram que o hidrogel intumesce lentamente, embora tenha sido mais rápido do que a taxa do polímero livre. Nos testes de dissolução, o hidrogel liberou o fármaco lenta e continuamente. Esta liberação lenta foi semelhante a observada nos testes de intumescimento e resultou em uma liberação controlada do fármaco. Assim, o dextrano 70 kDa é um polímero adequado para o desenvolvimento de hidrogéis como veículos para a liberação controlada de fármacos.