Micellar modification of drug stability: analysis of the effect of hexadecyltrimethylammonium halides on the rate of degradation of cephaclor

The intra- and intermolecular rates of degradation of cephaclor were determined with and without hexadecyltrimethylammonium bromide (CTABr). Micellar-derived spectral shifts were used to measure the association of the ionic forms as well as to determine the effect of CTABr on the apparent acid dissociation constant of the antibiotic. The rate of degradation of cephaclor increased with detergent and was salt sensitive. Micellar effects were analyzed quantitatively within the frame-work of the speudophase ion exchange model. All experimental data were fitted to this model which was used to predict the combined effects of pH and detergent concentration. Micelles increased the rate of OH- attack on cephaclor; most of the effect was due to the concentration of reagents in the micellar pseudophase. The intramolecular degradation was catalyzed 25-fold by micelles, and a working hypothesis to rationalize this effect is proposed. The results demonstrate that quantitative analysis can be utilized to assess and predict effects of detergents on drug stability.

The effect of bovine interferon-alpha I1 on pregnancy rate in heifers.

Bovine interferon-alpha I1 (bIFN-alpha) may be useful for enhancing fertility in sheep and cattle because it has extensive sequence homology with ovine and bovine trophoblast protein-1 and, like those proteins, extends corpus luteum lifespan. To test the effectiveness of bIFN-alpha to enhance fertility, several experiments were performed in which inseminated heifers were given i.m. injections of bIFN-alpha approximately at the time of embryo-mediated signals that result in maintenance of the corpus luteum. In Exp. 1, heifers given 20 mg of bIFN-alpha daily from d 14 to 17 tended (P less than .07) to have lower pregnancy rates at d 110 to 112 of gestation (36/75; 48% vs 43/72; 60%). Similar results were obtained in Exp. 2 when heifers received a single injection of 40 mg of bIFN-alpha or placebo at d 13 after estrus; pregnancy rates at d 42 were 39/104 (38%) for bIFN-alpha and 47/98 (48%) for placebo. In Exp. 3, heifers were given gradually increasing doses of bIFN-alpha or placebo from d 11 to 19, because such a regimen had been shown to reduce the number of heifers experiencing hyperthermia after bIFN-alpha injection. Pregnancy rates were 42/95 (44%) for bIFN-alpha and 62/111 (56%) for placebo. Across all three experiments, pregnancy rates were lower (P less than .01) for heifers treated with bIFN-alpha (117/274; 43%) than for heifers treated with placebo (152/281; 54%). In conclusion, these results demonstrate that, under the administration systems used, bIFN-alpha does not increase pregnancy rate, but rather tends to reduce it.

Protective effect of nickel chloride on superoxide damage: enhancement of CuZn superoxide dismutase affinity to the oxygen free radical.

The effect of nickel from soluble NiCl2 on Cu-Zn superoxide dismutase (SOD) activity, as well as on rate of nitro blue tetrazolium reduction, was studied in vitro since lipid peroxidation has been implicated in cell damage by nickel insoluble compounds, whose toxicity and carcinogenicity are well established. The physical and chemical nature of nickel compounds is one of the key determinations of its toxicity. Soluble nickel freely enter cells, but is just as readily excreted reducing the opportunity for production of lipid damage. Nickel from NiCl2 strongly activated SOD activity. In vitro addition of nickel chloride to a crude lung preparation altered the KM for SOD without changing the Vmax. Nickel chloride produced increased enzyme affinity to the substrate, because decreased (O2-) concentration that yields half-maximal velocity. The combination of nickel and SOD may contribute to stabilization of the particular conformation of SOD responsible for maximal catalytically activity.

Effect of benzylaminopurine (BAP) on clonal propagation rate of Curcuma longa L.

Curcuma longa L. is used in many countries for its flavor, and medicinal and cosmetic attributes, as well as for its peculiar starch characteristics. These factors have driven an interest in the in vitro propagation of this species, looking for germplasm bank maintenance, production of disease free plants, genetic variability induction from callus, and as a tool for starch research. However, there are few reports concerning the micropropagation of Curcuma longa. The in vitro propagation rate of this species, cultured under two benzylaminopurine (BAP) concentrations, was the aim of this research.

β-carotene attenuates the paradoxical effect of tobacco smoke on the mortality of rats after experimental myocardial infarction

The objective of this study was to investigate the effects of exposure to tobacco smoke (ETS) in rats that were or were not supplemented with dietary β-carotene (BC), on ventricular remodeling and survival after myocardial infarction (Ml). Rats (n = 189) were allocated to 4 groups: the control group, n = 45; group BC administered 500 mg/kg diet, n = 49, BC supplemented rats; group ETS, n - 55, rats exposed to tobacco smoke; and group BC+ETS, n = 40. Wistar rats weighing 10O g were administered one of the treatments until they weighed 200 to 250 g (∼5 wk). The ETS rats were exposed to cigarette smoke for 30 min 4 times/d, in a chamber connected to a smoking device. After reaching a weight of 200-250 g, rats were subjected to experimental MI (coronary artery occlusion) and mortality rates were determined over the next 105 d. In addition, echocardiographic, isolated heart, morphometrical, and biochemical studies were performed. Mortality data were tested using Kaplan-Meyer curves and other data by 2-way ANOVA. Survival rates were greater in the ETS group (58.2%) than in the control (33.3%) (P = 0.001) and BC+ETS rats (30.0%) (P = 0.007). The groups did not differ in the other comparisons. Left ventricular end-diastolic diameter normalized to body weight was greater and maximal systolic pressures were lower in the ETS groups than in non-ETS groups. Previous exposure to tobacco smoke induced a process of cardiac remodeling after MI. There is a paradoxical protector effect with tobacco smoke exposure, characterized by lower mortality, which is offset by BC supplementation. © 2005 American Society for Nutritional Sciences.

The effect of eccentric strength training on heart rate and on its variability during isometric exercise in healthy older men

The purpose of this study was to investigate if chronic eccentric strength training (ST) affects heart rate (HR) and heart rate variability (HRV) during sub-maximal isometric voluntary contractions (SIVC). The training group (TG) (9 men, 62 ± 2) was submitted to ST (12 weeks, 2 days/week, 2 - 4 sets of 8-12 repetitions at 75-80% peak torque (PT). The control group (CG) (8 men, 64 ± 4) did not perform ST. The HR and the HRV (RMSSD index) were evaluated during SIVC of the knee extension (15, 30 and 40% of PT). ST increased the eccentric torque only in TG, but did not change the isometric PT and the duration of SIVC. During SIVC, the HR response pattern and the RMSSD index were similar for both groups in pre- and post-training evaluations. Although ST increased the eccentric torque in the TG, it did not generate changes in HR or HRV. © Springer-Verlag 2008.

Effect of remifentanil hydrochloride administered via constant rate infusion on the minimum alveolar concentration of isoflurane in cats

Objective - To evaluate the effects of increasing doses of remifentanil hydrochloride administered via constant rate infusion (CRI) on the minimum alveolar concentration (MAC) of isoflurane in cats. Animals - 6 healthy adult cats. Procedures - For each cat, 2 experiments were performed (2-week interval). On each study day, anesthesia was induced and maintained with isoflurane; a catheter was placed in a cephalic vein for the administration of lactated Ringer's solution or remifentanil CRIs, and a catheter was placed in the jugular vein for collection of blood samples for blood gas analyses. On the first study day, individual basal MAC (MAC Basal) was determined for each cat. On the second study day, 3 remifentanil CRIs (0.25, 0.5, and 1.0 μg/kg/min) were administered (in ascending order); for each infusion, at least 30 minutes elapsed before determination of MAC (designated as MAC R0.25, MAC R0.5, and MAC R1.0, respectively). A 15-minute washout period was allowed between CRIs. A control MAC (MAC Control) was determined after the last remifentanil infusion. Results - Mean ± SD MAC Basal and MAC Control values at sea level did not differ significantly (1.66 ± 0.08% and 1.52 ± 0.21%, respectively). The MAC values determined for each remifentanil CRI did not differ significantly. However, MAC R0.25, MAC R0.5, and MAC R1.0, were significantly decreased, compared with MAC Basal, by 23.4 ± 79%, 29.8 ± 8.3%, and 26.0 ± 9.4%, respectively. Conclusions and Clinical Relevance - The 3 doses of remifentanil administered via CRI resulted in a similar degree of isoflurane MAC reduction in adult cats, indicating that a ceiling effect was achieved following administration of the lowest dose.

Effect of axial loads on implant-supported partial fixed prostheses by strain gauge analysis

Objectives: The present study used strain gauge analysis to perform an in vitro evaluation of the effect of axial loading on 3 elements of implant-supported partial fixed prostheses, varying the type of prosthetic cylinder and the loading points. Material and methods: Three internal hexagon implants were linearly embedded in a polyurethane block. Microunit abutments were connected to the implants applying a torque of 20 Ncm, and prefabricated Co-Cr cylinders and plastic prosthetic cylinders were screwed onto the abutments, which received standard patterns cast in Co-Cr alloy (n = 5). Four strain gauges (SG) were bonded onto the surface of the block tangentially to the implants, SG 01 mesially to implant 1, SG 02 and SG 03 mesially and distally to implant 2, respectively, and SG 04 distally to implant 3. Each metallic structure was screwed onto the abutments with a 10 Ncm torque and an axial load of 30 kg was applied at five predetermined points (A, B, C, D, E). The data obtained from the strain gauge analyses were analyzed statistically by RM ANOVA and Tukey's test, with a level of significance of p<0.05. Results: There was a significant difference for the loading point (p=0.0001), with point B generating the smallest microdeformation (239.49 με) and point D the highest (442.77 με). No significant difference was found for the cylinder type (p=0.748). Conclusions: It was concluded that the type of cylinder did not affect in the magnitude of microdeformation, but the axial loading location influenced this magnitude.

Effect of follicle age on conception rate in beef heifers

The objective of this study was to determine the effect of age of the ovulatory follicle on fertility in beef heifers. Ovulation was synchronized with the 5 d CO-Synch + controlled intravaginal drug release (CIDR) program in heifers in Montana (MT; n = 162, Hereford and Angus Crossbred) and Ohio (OH; n = 170, Angus Crossbred). All heifers received estradiol benzoate (EB; 1 mg/500 kg BW, [i.m.]) 6 d after the final GnRH of the synchronization program to induce follicular atresia and emergence of a new follicular wave (NFW) followed by prostaglandin F2 alpha (PGF(2 alpha); 25 mg, i.m.) administration either 5 d (young follicle [YF]; n = 158) or 9 d (mature follicle [MF]; n = 174) after EB. Estrous detection was performed for 5 d after PGF(2 alpha) with AI approximately 12 h after onset of estrus. Ovarian ultrasonography (MT location only) was performed in YF and MF at EB, 5 d after EB, PGF(2 alpha), and AI. Heifers in MT (n = 20) and OH (n = 18) that were not presynchronized or did not initiate a NFW were excluded from further analyses, resulting in 142 and 152 heifers in MT and OH, respectively. Heifers from the MF treatment in MT that initiated a second NFW after EB but before PGF(2 alpha) (MF2; n = 14) were excluded from the primary analysis. In the secondary analysis, the MF2 group was compared to MF and YF treatments in MT. Estrous response was similar (90%; 252/280) between treatments and locations. Proestrus interval (from PGF(2 alpha) to estrus) and age of the ovulatory follicle at AI were similar for MF heifers between locations (54.6 +/- 1.7 h and 8.3 +/- 0.07 h) but were greater (P < 0.01) for YF heifers in OH (78.5 +/- 1.4 h and 5.3 +/- 0.06 h) than MT (67.4 +/- 1.6 h and 4.8 +/- 0.06 h; treatment x location, P < 0.01). However, conception rate did not differ for MF (63.8%; 74/116) and YF (67.0%; 91/136) treatments. In the MT heifers, follicle size and follicle age atAI in the YF treatment (10.4 +/- 0.15 mm and 4.8 +/- 0.06 d, respectively) was less (P < 0.01) than in the MF treatment (11.0 +/- 0.18 mm and 8.3 +/- 0.11 d, respectively), but conception rate to AI did not differ between treatments in MT. In the MF2 group proestrus interval was greater (P < 0.01); hence, diameter of the ovulatory follicle and age were similar to that for the YF treatment. Conception rate to AI did not differ between MF2, MF, and YF (61.5, 63.3, and 64.7%, respectively) in MT. In conclusion, manipulation of age of the nonpersistent ovulatory follicle at spontaneous ovulation did not influence conception rate.

Effect of progesterone concentrations, follicle diameter, timing of artificial insemination, and ovulatory stimulus on pregnancy rate to synchronized artificial insemination in postpubertal Nellore heifers

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

The effect of follicle age on pregnancy rate in beef cows

The effect of the age of the ovulatory follicle on fertility in beef cows was investigated. Multiparous (n = 171) and primiparous (n = 129) postpartum beef cows in 2 groups (G1 and G2) received estradiol benzoate (EB; 1 mg/500 kg BW, intramuscular [i.m.]) 5.5 d (G1; n = 162) and 6.5 d (G2; n = 138) after the final GnRH of a synchronization program (5d CO-Synch + CIDR) to induce emergence of a new follicular wave (NFW), followed by prostaglandin F2 alpha (PGF2 alpha; 25 mg, i.m.) administration either 5.5 d (young follicle, YF; n = 155) or 9.5 d (mature follicle, MF; n = 145) after EB. Estrous detection coupled with AI 12 h later (estrus-AI) was performed for 60 h (MF) and 84 h (YF) after PGF(2 alpha); cows not detected in estrus within this period received timed AI (TAI) coupled with GnRH at 72 and 96 h, respectively. Within the first 72 h after PGF(2 alpha), more (P < 0.01) cows in the MF (76.3%) than YF treatment (47.7%) exhibited estrus, but through 96 h, the proportion detected in estrus (P < 0.05) and interval from PGF(2 alpha) to estrus (P < 0.01) were greater in the YF than MF treatment (88.6% vs. 76.3%, 78.9 +/- 0.8 vs. 57.5 +/- 1.6 h, respectively). Age of the ovulatory follicle at AI was greater (P < 0.01) in the MF (9.32 +/- 0.04 d) than YF (6.26 +/- 0.02 d) treatment, but follicle diameter at AI and pregnancy rates did not differ between MF (13.1 +/- 0.2 mm; 72.0%) and YF (12.9 +/- 0.1 mm; 67.1%) treatments. Regardless of treatment, the diameter of the ovulatory follicle at AI and pregnancy rate were greater (P < 0.01) with estrus-AI (13.1 +/- 0.1 mm; 75.0%) than TAI (12.6 +/- 0.2 mm; 55.4%). Cows in the MF treatment that initiated a second NFW after EB but before PGF(2 alpha) (MF2; n = 47) were induced to ovulate with GnRH and TAI at 72h, when ovulatory follicles were 4 d old and 10.2 +/- 0.2 mm in diameter. Pregnancy rate for TAI (51.1%) in MF2 did not differ from TAI pregnancy rate (55.4%) across the MF and YF treatments. In summary, the age of the ovulatory follicle affected interval to estrus and AI but did not influence pregnancy rate in suckled beef cows.

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)